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Advanced Synthesis & Catalysis

Wiley Online Library : Advanced Synthesis & Catalysis

Published: 2017-11-10T00:00:00-05:00


Metal-Free One-Pot Synthesis of (Tetrahydro)Quinolines through Three-Component Assembly of Arenediazonium Salts, Nitriles, and Styrenes


A highly efficient and convenient metal-free, one-pot synthesis of diversely substituted (tetrahydro)quinolines has been achieved through a three-component assembly reaction of arenediazonium salts, nitriles, and styrenes. In sharp contrast to the prior works with the same reagent blend, the formation of N-arylnitrilium intermediates from arenediazonium salts and nitriles was followed by reaction with styrenes, leading to 3,4-dihydroquinolinium salts as a common intermediate. These could be further transformed to quinolines and tetrahydroquinolines depending on the reaction conditions. The advantages of this protocol include its simplicity, metal-free and mild conditions, readily available starting materials, and good functional group tolerance.

Sunlight-promoted direct irradiation of N-centred anion: the photocatalyst-free synthesis of pyrazoles in water


A practical method through sunlight mediated annulation of α, β-unsaturated hydrazones has been developed for the synthesis of pyrazole. Based on the analysis of UV-Vis absorption of the substrate, the reaction was designed to avoid the use of external photocatalysis and proceeds via direct irradiation of N-centred anion by sunlight. The key features of this reaction include operational simplicity, readily available reagents, and amenability to gram-scale synthesis.

Metal-free Thiolation of Imidazopyridines with Functionalized Haloalkanes Using Elemental Sulfur


The assembly of two functional molecules via a sulfur-linking atom allows for access to a diverse array of thioether-containing compounds. Herein, we disclose a metal-free thiolation of imidazopyridines with a variety of functionalized haloalkanes using elemental sulfur.

Copper-Catalyzed Dehydrative Cyclization of 1-(2-Hydroxyphenyl)-propargyl Alcohols with P(O)H Compounds for the Synthesis of 2-Phosphorylmethyl Benzofurans


A Cu(MeCN)4BF4-catalyzed dehydrative reaction of 1-(2-hydroxyphenyl)propargyl alcohols with diarylphosphine oxides has been developed to provide an efficient synthesis of phosphorylated benzofurans in good to high yields. In the presence of a catalytic amount of an organic base, a variety of H-phosphonates and H-phosphinates can also be employed as good substrates to produce the corresponding products in moderate yields. The reaction has significant economical and ecological advantages since the formation of a new Csp3−P bond and the benzofuran framwork could both be achieved using an inexpensive copper catalyst with water produced as the sole byproduct. The synthetic transformations of the product have also been demonstrated.

Microwave-Assisted Synthesis of Benzimidazole-Linked Indoline and Indole Hybrids from C-2-Linked o-Amino Benzyl Benzimidazoles


An efficient and novel synthesis of benzimidazole-linked indoline hybrids via an unconventional Pictet-Spengler type condensation of C-2 linked o-aminobenzyl benzimidazole with aldehydes and ketones under microwave irradiation is explored. The key condensation step consists of acid catalyzed imine generation followed by intramolecular C-C bond formation through unique reactivity of benzimidazole moiety. The scope of this method is further extended to synthesize tetracyclic pyrrolo indole benzoimidazole carboxylates through 2-carboxyaldehydes.

Intermolecular Rhodium(II)-Catalyzed Allylic C(sp3)-H Amination of Cyclic Enamides


The intermolecular Rh(II)-catalyzed C(sp3)–H amination of enamides gives access to new 4-aminopiperidine derivatives that are useful building blocks in medicinal chemistry. This efficient transformation proceeds at room temperature with complete regio- and chemoselectivity in favor of the allylic C(sp3)–H bond, and has a broad functional group tolerance. In addition, the matched combination of the chiral Rh2(S-nta)4 (nta = (S)-N-1,8-naphthoylalanine) with an optically pure (S)-sulfonimidamide allows isolation of allylic amines with excellent stereocontrol.

Copper/Iron-Cocatalyzed Cascade Perfluoroalkylation/Cyclization of 1,6-Enynes with Iodoperfluoroalkanes


A copper/iron-cocatalyzed fluoroalkylative cyclization of 1,6-enynes with readily available iodoperfluoroalkanes reagents for the synthesis of the corresponding fluoroalkylated pyrrolidines and benzofuran derivatives is reported. This novel protocol provides a mild method for the construction of Csp3-CF2 and exocyclic double bonds in one step with high regio- and stereo-selectivities.

Potassium 2-oxo-3-enoates as Effective and Versatile Surrogates for α, β-Unsaturated Aldehydes in NHC-Catalyzed Asymmetric Reactions


Potassium 2-oxo-3-enoates, which are readily prepared at scale and easily stored, have been found to be effective and versatile surrogates for α,β-unsaturated aldehydes in NHC-catalyzed asymmetric reactions. Promoted by chiral N-heterocyclic carbenes combined with LiCl, these easy-to-handle solid salts could release of CO2 and then undergo asymmetric reactions via homoenolate and α,β-unsaturated acyl azolium intermediate. The reactions have broad substrate scopes with high enantioselectivities.

Manufacture of Citronellal by Rhodium Catalysed Homogeneous Hydrogenation of Neral


The highly chemoselective hydrogenation of neral affording citronellal is described. The reaction has been conducted with homogeneous rhodium complexes. Among a set of ancillary diphosphane ligands tested Xantphos was found to be superior. The relevant precatalyst has been generated from neutral metal sources such as Rh(acac)(CO)2 or the carbon monoxide free rhodium source Rh(acac)(cod) in the absence of any base. High activity and chemoselectivity in favour of the desired citronellal is achieved at 0.1 MPa and room temperature. Under the same conditions also geranial is reduced to citronellal. The addition of carbon monoxide to the hydrogen stream as used in an industrial process is not necessary.

Supported Palladium Nanoparticles Catalyzed Reductive Carbonylation of Nitroarenes to N-Arylformamides


A facile reductive carbonylation reaction of nitroarenes to N-arylformamide synthesis was investigated under polymer supported palladium (Pd@PS) nanoparticles catalyzed conditions. Dual role of oxalic acid dihydrate ((CO2H)2.2H2O) as H2 source for hydrogenation and CO source for carbonylation reaction for desire products synthesis was critically investigated under favorable DMF solvent conditions. Several cross experiments were performed to establish the best possible hypothesis for the proposed mechanism and understanding about the involvement of CO in the reaction pathway. Further, ortho-substituted nitroarenes were found to be highly specific for facile para-hydroxylation to give corresponding para-hydroxy N-aryl formamides.

Synthesis of Fused-Pyrazines via Palladium-Catalyzed Double Benzyl Isocyanide Insertion and Cross-Dehydrogenative Coupling


A palladium-catalyzed cascade reaction has been realized for the synthesis of 5H-pyrrolo[2,3-b]pyrazines and 5H-pyrazino[2,3-b]indoles with benzyl isocyanide by choosing o-pivaloyloximes or o-iodoanilines as a suitable substrate. The key steps involved are (i) oxidative addition of palladium through N-O or C-I cleavage; (ii) migratory double isocyanide insertion; and (iii) cross-dehydrogenative coupling. Notable features are good functional group tolerance, formation of three C-C and one C-N bonds.

Cyclopropanation of Benzene Rings by Oxidatively Generated α-Oxo Gold Carbene: One-Pot Access to Tetrahydropyranone-Fused Cycloheptatrienes from Propargyl Benzyl Ethers


Cyclopropanations of benzene rings by oxidatively generated α-oxo gold carbenes are for the first time demonstrated in a Buchner reaction, in which readily available propargyl benzyl ethers are converted in one-pot to tetrahydropyranone-fused cycloheptatrienes via sequential oxidative gold catalysis and base-promoted isomerization. Additional examples of arene cyclopropanations without fragmentation of the cyclopropane ring are also realized.

A Sustainable Synthesis of Asymmetric Phenazines and Phenoxazinones Mediated by CotA-Laccase


An efficient and sustainable one-step procedure for the synthesis of new asymmetric phenazines and phenoxazinones from commercially available ortho-substituted diamines and ortho-substituted hydroxyamines is reported. In this study we have expanded the substrate scope of CotA-laccase-catalyzed aerobic oxidations through the use of aromatic amines presenting variable functional groups, including N-substitution, contributing to the rational synthesis of different heterocyclic scaffolds. The transformations proceed smoothly through a cascade of oxidative reactions to the benzoquinonediimine interme-diates followed by nucleophilic addition, intramolecular cyclization and aromatization, all performed in mild conditions.

Rhodium(I)-Catalyzed Arylation/Dehydroxylation of tert-Propargylic Alcohols Leading to Tetrasubstituted Allenes


Diverse tetrasubstituted allenes are obtained selectively by the reaction of tert-propargylic alcohols and arylboroxines under rhodium catalysis. The reaction is assumed to proceed through an arylation/dehydroxylation process, which involves β-hydroxide elimination of a β-hydroxy alkenyl-rhodium intermediate that is generated by regioselective arylrhodation of the tert-propargylic alcohol. In addition, when enantioenriched propargylic alcohol was used to prepare optically active allene, high efficiency of central-to-axial chirality transfer was observed. The application of current method to structural modification of pharmaceutical drugs was also showcased by a highly diastereoselective transformation of mifepristone.

Organocatalytic Nitroaldol Reaction Associated with Deuterium-Labeling


A deuterium-labeling reaction of nitroalkanes in deuterium oxide and the subsequent nitroaldol reaction have been accomplished under basic and organocatalytic conditions to provide the deuterium-labeled beta-nitroalcohols in high yields and high deuterium contents. beta-Deuterated beta-nitroalcohols could be smoothly obtained from the reaction of nitroalkanes and various electrophiles using the easily-removal basic resin WA30. Furthermore, the asymmetric nitroaldol reaction using nitromethane and alpha-keto esters as electrophiles in the presence of a quinine-derived organocatalyst in deuterium oxide could provide the desired beta-deuterated nitroalcohol derivatives with high enantioselectivities.

Synthesis of Carbazoles from 2-Iodobiphenyls by Palladium-Catalyzed C–H Activation and Amination with Diaziridinone


A facile and efficient approach has been developed for the synthesis of carbazoles from 2-iodobiphenyls and diaziridinone under palladium catalysis. A wide range of carbazoles were synthesized in good to excellent yields, and indole derivatives were obtained by using styrenes as the substrate. The palladacycles obtained from 2-iodobiphenyls acted as the key intermediate, and the reaction should proceed via a tandem Pd-catalyzed C–H activation/dual C–N bond formation sequence.

Lewis Acid Catalyzed Reductive Amination of Aldehydes and Ketones with N,N-Dimethylformamide as Dimethyl Amino Source, Reductant and Solvent


A practical zinc acetate dihydrate catalyzed reductive amination of various carbonyl compounds with DMF as Me2N source, reductant and solvent is developed. This reaction shows broad substrate scope, good functionality tolerance, avoids pressure-proof reactor and column chromatograph isolation with up to 98 % yield, to make it an attractive method for the preparation of N,N-dimethyl tertiary amines.

Copper-Mediated Tandem C(sp2)-H Amination and Annulation of Arenes with 2-Aminopyridines: Synthesis of Pyrido-fused Quinazolinone Derivatives


An efficient and convenient copper-mediated tandem C(sp2)-H amination and annulation of arenes with 2-aminopyridines to provide 11H-pyrido[2,1-b]quinazolin-11-ones has been developed. A variety of benzamides and 2-aminopyridines bearing different substituents are compatible with this transformation

Asymmetric Vinylogous Mannich-Type Addition of alfa,alfa-Dicyanoalkenes to alfa-Fluoroalkyl Sulfinyl Imines


Abstract. The asymmetric vinylogous Mannich reaction (AVMR) of alfa,alfa-dicyanoalkenes with alfa-fluoroalkyl sulfinyl imines has been successfully accomplished. This transformation is unprecedented with fluorinated imines at the same time as the use of dicyanoalkenes in AVMR has been scarcely reported. Several fluorinated sulfinyl imines are compatible with the process, which gaves access to a family of chiral fluorinated amines with excellent level of stereocontrol. Interestingly, the selectivity found in our protocol is reverse to that encountered in analogous AVMR previously reported. Additionally, the synthetic applicability of the addition products has been exemplified with several transformations showing the particular reactivity of the dicyanoalkene moiety of these alfa-fluorinated amines.

Synthesis of Cyclobutene-Fused Eight-Membered Carbocycles through Gold-Catalyzed Intramolecular Enyne [2+2] Cycloaddition


Cationic gold(I) complexes with hollow-shaped triethynylphosphine ligands efficiently catalyzed intramolecular [2+2] cycloaddition of 1,9-enynes to afford cyclobutene-fused eight-membered carbocycles that were difficult to synthesize by other catalytic systems. Various 1,9-enynes with carbon linkers with or without a fused ring underwent efficient [2+2] cycloaddition with 5 mol% of the Au catalyst bearing the triarylmethyl-end-capped triethynylphosphine in CH2Cl2 at rt in the presence of MS 4A as an additive. More challenging 1,9-enyne substrates with fully saturated acyclic carbon linkers underwent eight-membered ring formation at 60 °C in ClCH2CH2Cl in the absence of MS 4A, forming monocyclic 1,3-dienes as major products.

Acid/Base-Co-Catalyzed Direct Oxidative α-Amination of Cyclic Ketones: Using Molecular Oxygen as the Oxidant


A novel acid/base-co-catalyzed direct intermolecular α-amination of various cyclic ketones has been developed for the first time. The reaction employs molecular oxygen as the sole oxidant under metal-free conditions. The reaction tolerates a wide range of various anilines, especially primary diamine derivatives, and provides a simple and efficient method for the constructions of α-amino enones and benzodiazepine derivatives in a single step.

Selective Asymmetric Transfer Hydrogenation of α-Substituted Acetophenones with Bifunctional Oxo-Tethered Ruthenium(II) Catalysts


A practical method for the asymmetric transfer hydrogenation of α-substituted ketones was developed utilizing oxo-tethered N-sulfonyldiamine-ruthenium complexes. Reduction by HCO2H and HCO2K in a mixed solvent of EtOAc/H2O allowed for the selective synthesis of halohydrins from 2-bromoacetophenone (98%) and 2-chloroacetophenone (>99%), leading to suppressed undesired side reactions stemming from formylation under the typical reaction conditions using an azeotropic 5:2 mixture of HCO2H and Et3N. A range of functional groups, such as halogens, methoxy, nitro, dimethylamino, and ester groups, were well tolerated, highlighting the potential of this method. Nearly complete selectivity with a preferable ee was maintained even with a substrate/catalyst (S/C) ratio of 5000. This catalyst system was also effective for the asymmetric reduction of α-sulfonated ketones without eroding the leaving group.

Enantioselective Synthesis of β-Aminotetralins via Chiral Phosphoric Acid-catalyzed Reductive Amination of β-Tetralones


A new protocol for the synthesis of chiral β-aminotetralins has been developed via chiral phosphoric acid-catalyzed asymmetric reductive amination of β-tetralones using a Hantzsch ester as an organic hydride donor. Various chiral β-aminotetralins were obtained in good yields with good to high enantioselectivities. Furthermore, the utility of our new protocol was successfully demonstrated in the enantioselective synthesis of rotigotine.

Direct ortho-Acyloxylation of Arenes and Alkenes by Cobalt Catalysis


An efficient protocol of cobalt-catalyzed acyloxylation of arenes and alkenes with the assistance of 8-aminoquinolyl auxiliary is reported. In this transformation, benzoic acids, alkenyl acids, and aliphatic acids could be readily involved to afford structurally diverse esters. It is worth noting that the Ag2SO4 oxidant is renewable and the directing group could be removed and recycled. The strategy represents the first successful example of transition-metal-catalyzed acyloxylation of alkenyl carboxamides C(sp2)-H bonds with carboxylic acids.

Enantioselective Oxy-Heck-Matsuda Arylations: Expeditious Synthesis of Dihydrobenzofuran Systems and Total Synthesis of the Neolignan (-)-Conocarpan


This work discloses the first examples of an effective enantioselective oxy-Heck-Matsuda reaction using a variety of styrenic olefins to generate chiral dihydrobenzofurans. The reaction proceeds in moderate to good yields, with high trans diastereoselectivity (up to 20:1) in enantioselectivities up to 90:10 using the N,N-ligand pyrimidine-bisoxazoline (PyriBox) L7. The oxy-Heck-Matsuda reactions are carried out under mild conditions and rather low catalyst loading. The feasibility and practicality of the process is demonstrated by a concise total synthesis of the neolignan (-)-conocarpan. X-ray diffraction of an advanced brominated intermediate in route to (-)-conocarpan has allowed unequivocal assignment of the absolute stereochemistry of the oxy-Heck-Matsuda aryl dihydrobenzofuran adducts. A rationale for the mechanism operating in these enantioselective oxy-Heck-Matsuda reactions is also presented.

Copper Catalysis for Nicotinate Synthesis through β-Alkenylation/Cyclization of Saturated Ketones with β-Enamino Esters


The first example of Cu-catalyzed and 4-OH-TEMPO mediated intermolecular [3 + 3] annulation of saturated ketones with β-enamino esters is reported, which was successfully applied for the synthesis of versatile nicotinates through sequential β-C(sp3)-H bond alkenylation, enamine-carbonyl condensation and aromatization. This protocol tolerates a variety of functional groups, thus provides a practical and efficient method for the constuction of 5H-chromeno[4,3-b]pyridin-5-one skeletons.

Use of Nucleoside Phosphorylases for the Preparation of Purine and Pyrimidine 2′-Deoxynucleosides


Enzymatic transglycosylation - a transfer of the carbohydrate moiety from one heterocyclic base to another - is being actively developed and applied for the synthesis of practically important nucleosides. This reaction is catalyzed by nucleoside phosphorylases (NPs), which are responsible for reversible phosphorolysis of nucleosides to yield the corresponding heterocyclic bases and monosaccharide 1-phosphates. We found that 7-methyl-2′-deoxyguanosine (7-Me-dGuo) is an efficient and novel donor of the 2-deoxyribose moiety in the enzymatic transglycosylation for the synthesis of purine and pyrimidine 2'-deoxyribonucleosides in excellent yields. Unlike 7-methylguanosine, its 2ʹ-deoxy derivative is dramatically less stable. Fortunately, we have found that 7-methyl-2′-deoxyguanosine hydroiodide may be stored for 24 h in Тris-HCl buffer (pH 7.5) at room temperature without significant decomposition. In order to optimize the reagent ratio, a series of analytical transglycosylation reactions were conducted at ambient temperature. According to HPLC analysis of transglycosylation reactions, the product 5-ethyl-2′-deoxyuridine (5-Et-dUrd) was obtained in high yield (84-93%) by using a small excess (1.5 and 2.0 equiv.) of 7-Me-dGuo over 5-ethyluracil (5-Et-Ura) and 0.5 equiv. of inorganic phosphate. Thymidine is a less effective precursor of α-D-2-deoxyribofuranose-1-phosphate (dRib-1p) compared to 7-Me-dGuo. We synthesized 2'-deoxyuridine, 5-Et-dUrd, 2'-deoxyadenosine and 2'-deoxyinosine on a semi-preparative scale using the optimized reagents ratio (1.5:1:0.5) in high yield. Unlike other transglycosylation reactions, the synthesis of 2-chloro-2'-deoxyadenosine was performed in heterogeneous medium because of the poor solubility of initial 2-chloro-6-aminopurine. Nevertheless, this nucleoside was prepared in good yield. The developed enzymatic procedure for the preparation of 2'-deoxynucleosides may compete with the known chemical approaches.

Dimerization of Phenylalanine: An Approach to Thiazoles and Oxazoles Involved S/O-Insertion


We herein describe the development of a dimerization procedure for amino acids to prepare 2,5-disubstituted thiazoles and oxazoles in the presence of Na2S•9H2O and H2O, respectively. These approaches enabled the direct formation of five-membered ring systems bearing two different heteroatoms from two amino acids units. Mechanically, decarboxylation, deamination, S/O insertion, cyclization and gradient oxidation processes were involved in the oligomer formation.

One-pot Domino Synthesis of Diarylalkynes/1,4-Diaryl-1,3-diynes by [9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene]Copper(I) Iodine–Palladium(II) Acetate Catalyzed Double Sonogashira-type Reaction


Abstract. The low loading combination of complex [9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene]copper (I) iodide and simple ligand-free palladium (II) acetate was found efficient for the domino synthesis of diarylalkynes by the reaction of aryl halides with trimethylsilylethynylene or bis(trimethylsilyl)acetylene in a single-step procedure. The unsymmetrical diarylalkynes can be obtained through a one-pot two-step approach. The reactions of aryl bromides with 1,4-bis(trimethylsilyl)butadiyne also furnished the corresponding 1,4-diaryl-1,3-diynes in a similar fashion. This route to diarylalkynes and 1,4-diaryl-1,3-diynes is complementary to previously reported synthetic procedures.

Computationally-led Ligand Modification using Interplay between Theory and Experiments: Highly Active Chiral Rhodium Catalyst Controlled by Electronic Effects and CH–π Interactions


A novel chiral ligand for the rhodium-catalyzed asymmetric 1,4-addition of arylboronic acid to a coumarin substrate that could markedly reduce catalyst loading was developed using interplay between theoretical and experimental approaches. Evaluation of the transition states for insertion and for hydrolysis of intermediate complexes (which were emphasized in response to the experimental results) using DFT calculations at the B97D/6-31G(d) with the LANL2DZ basis set for rhodium revealed that: a) the electron-poor nature of the ligands; and b) CH–π interactions between the ligand and coumarin substrates played significant roles in both acceleration of insertion and inhibition of ArB(OH)2 decomposition (protodeboronation). The computationally-designed novel ligand, incorporating above information, decreased the catalyst loading up to 0.025 mol% (S/C = 4,000), which is less than one one-hundredth relative to past catalyst loadings of typically 3 mol%, with almost complete enantioselectivity. Furthermore, the gram-scale synthesis of the urological drug, (R)-Tolterodine (L)-tartrate, was demonstrated without the need of intermediary purification.

Palladium-catalysed O-Allylation of α-Hydroxyphosphonates: An Expedient entry into Phosphono-oxaheterocycles


We report here an unprecedented palladium-catalysed O-allylation of α-hydroxyphosphonates. The method was eventually included in a sequential Pudovik/Tsuji-Trost type O-allylation/Ring-Closing Metathesis to afford a variety of phosphorylated heterocycles of various sizes ranging from 5 to 16 starting from readily available aldehydes.

Metal-Free Decarboxylative Trichlorination of Alkynyl Carboxylic Acids : Synthesis of Trichloromethylketones


2,2,2-Trichloroacetophenone derivatives were synthesized via decarboxylative trichlorination from arylpropiolic acids and trichloroisocyanuric acid (TCCA). The reaction was conducted in the presence of H2O (water) at room temperature, and afforded the desired products in good yields. The reaction showed good functional group tolerance towards halides, cyano, nitro, ketone, ester and aldehyde groups.In addition, 2,2,2-trichloroacetophenone derivatives were readily transformed into esters, amides, and hydrazides. Based on experiments with H218O (water-18O), we proposed a cationic reaction pathway in the mechanism and suggested two different pathways for aryl- and alkyl-substituted propiolic acids.

Palladium Catalyzed C–C and C–N Bond Formation via ortho C–H Activation and Decarboxylative Strategy: A Practical Approach towards N–Acylated Indoles


A concerted palladium catalyzed C–H activation and decarboxylative strategy has been explored for the efficient synthesis of N–acylated indoles. The process allows a facile step- and atom-economic assembly of 3-arylated indole ring from inexpensive and readily available anilides and cinnamic acids as reacting partners.

Nickel/Zinc Iodide Co-catalytic Asymmetric [2+2] Cycloaddition Reactions of Azabenzonorbornadienes with Terminal Alkynes


The asymmetric [2+2] cycloaddition reactions of alkenes with alkynes are interesting as it has provided a powerful method for the construction of fused and strained cyclobutenes with multiple chiral centers. In this paper, we report the establishment of a dual catalysts system comprising nickel and zinc, which allowed the asymmetric [2+2] cycloaddition reactions of azabenzonorbornadienes with terminal alkynes in good yields and excellent enantioselectivities.

Lewis basicity of water for a selective monodehalogenation of α,α-dihaloketones to α-haloketones and mechanistic study


Abstract. The Lewis base character of the greenest reagent water has been explored over its nucleophilic property for an organic transformation. Utilizing this concept, a new strategy for the highly controlled and selective mono-dehalogenation of -dihaloketones has been discovered and reported in this manuscript. Extending this concept, first direct conversion of propargylic acetates to corresponding -iodoketones via -dihaloketones has also been efficiently achieved under metal free conditions. During the later process, water has been concurrently employed as a nucleophile and a Lewis base. Employing this type of dual reactivity of water may be for the first time in the context of organic synthesis. Control experiments supported the involvement of the enoalte as an intermediate during the monodehalogneation process.

Photoredox Catalysis in C-S bonds Construction: Recent Progress in Photo-catalyzed Formation of Sulfones and Sulfoxides


The spring up of radical chemistry as well as green chemistry in organic synthesis has initiated the interest in photochemistry over the past decade. With catalytic amount of photoredox catalysts under irradiation, high active radical species is produced, which could trigger the subsequent organic transformations smoothly. Among the various photoredox reactions, photo-catalytic C-S bond formations continues to thrive, as C-S bond is indispensable in many important biological and pharmaceutical compounds. Great attention has been drawn in this area with series of papers on sulfone and sulfoxide skeletons synthesis under light irradiations published in these years. This review summarizing the recent advances in photo-catalyzed sulfones and sulfoxides formation is arranged by reaction types together with sulfur source covering sulfonylation and sulfinylation reactions. It intends to bring readers a comprehensive understanding on photo-catalytic C-S bond formation and make help for future research. 1 Introduction 2 Sulfonylation 2.1 Arylsulfinic Acids or Salts as Sulfonyl Source 2.2 Sulfonyl Chlorides as Sulfonyl Source 2.3 Sulfonylhydrazides as Sulfonyl Source 2.4 Sulfur Dioxide as Sulfonyl Source and the Others 3 Sulfinylation 4 Summary and Prospects

Gold Catalyzed Dehydrogenative Cycloisomerization of 1,4-Enyne Esters to 3,5-Disubstituted Phenol Derivatives


A synthetic method to prepare synthetically important 3,5-disubstituted phenol derivatives that relies on the sequential Au(I)-catalyzed dehydrogenative cycloisomerization of 1,4-enyne esters in the presence of 3,4-dichloro-5,6-dicyanobenzoquinone (DDQ) or N-fluorobenzenesulfonimide (NFSI) is described. The synthetic versatility of the methodology was exemplified by a gram-scale reaction of one example, the ease to realize subsequent functional transformations of the adduct, and the application of the method to the synthesis of the bioactive molecule LUF5771.

Organocatalytic Enantioselective Friedel-Crafts Alkylation/Lactonization Reaction of Hydroxyindoles with Methylene Oxindoles


The indole benzene ring functionalization was achieved using an organocatalytic enantioselective Friedel-Crafts alkylation/lactonization reaction of hydroxyindoles with a variety of substituted methylene oxindoles. This reaction was applicable to indoles with the hydroxy group substituted at the different positions of the benzene ring, and the corresponding pyrrolodihydrocoumarins were obtained in moderate to high yields (37-99%) with high stereoselectivities (up to 99% ee and >20:1 dr) in most cases. A scale-up reaction and derivation of the representative products were also carried out to investigate the usefulness of this protocol.

Stereoselective One-Pot Sequential Dehydrochlorination/trans-Hydrofluorination Reaction of β-Chloro-α,β-unsaturated Aldehydes or Ketones: Facile Access to (Z)-β-Fluoro-β-arylenals/β-Fluoro-β-arylenones


The monofluoroalkene substructure shows a high potential as a fluorinated synthon in organic synthesis. However, control of the Z/E stereoselectivity of multi-substituted monofluoroalkene products in one-pot reaction still remains a challenge. An unprecedented one-pot approach for the highly regio- and stereoselective preparation of functionalized (Z)-β-monofluoro tri-substituted alkenes from readily available β-chloro-α,β-unsaturated aldehydes or ketones has been explored. Mechanistic studies demonstrated the reaction initiated from dehydrochlorination of the substrates to give alkynyl aldehydes/ketones, followed by their trans-hydrofluorination. It is worth mentioning that fluorinating reagent with suitable basicity and nucleophilicity plays a key role in promoting the formation of (Z)-β-fluoro-β-aryl tri-substituted monofluoroalkenes.

A Systematic Analysis of the Substrate Scope of (S)- and (R)-Selective Amine Transaminases


Amine transaminases (ATAs) emerged as an important group of biocatalysts for the synthesis of optically pure amines over the past few decades. In the same way, the amount of available data for ATA-catalyzed reactions increased significantly, forming the basis for a deeper understanding of this versatile group of enzymes. This data provides a high potential for relevant information if they can be structured and analyzed appropriately, especially for the identification of suitable ATAs for a certain reaction of interest. Following this intention, we started to collect reaction data from the literature for five (S)-selective and seven (R)-selective ATAs, focusing on conversion and enantiomeric excess values as important indicators for activity and selectivity. This resulted in a data collection of almost 500 ATA-catalyzed reactions subdivided into four distinctive substrate classes. Our comparative analysis using a data processing system based on function point analysis created a ranking of the most suitable ATAs for each substrate class, which is illustrated by graphics enabling the quick identification of matching enzymes and substrate combinations. This is accompanied by detailed information from the collected literature to serve as further guidance to choose the most suitable ATA for a reaction of interest. In addition, the presented categorization algorithm is provided in form of a free accessible R script that allows a simple reproduction of analysis results as well as the application for further groups of enantioselective biocatalysts.

Synthesis of Main-chain Ionic Polymers of Chiral Imidazolidinone Organocatalysts and Their Application to Asymmetric Diels–Alder Reactions


Main-chain ionic polymers incorporating chiral imidazolidinone moieties in the polymer main chain were successfully synthesized by the polyaddition reaction of a chiral imidazolidinone dimer with a disulfonic acid. The organocatalytic activities of these polymers were investigated in the asymmetric Diels–Alder reaction between trans-cinnamaldehyde and 1,3-cyclopentadiene. The catalytic performance of the polymers was found to be sensitive to the chemical structure of the disulfonate units and the imidazolidinone dimer. With the use of these heterogeneous polymeric chiral organocatalysts, enantioselectivities of up to 99% for the endo isomer were obtained. This result was higher than those obtained with corresponding monomeric and dimeric counterparts in a homogeneous solution. The polymeric chiral organocatalyst was recovered and reused several times, maintaining its high enantioselectivity.

Organocatalyzed enantioselective aldol and Henry reactions starting from alcohols


Pioneering aldol and Henry reactions starting from alcohols are described. The aldol reaction has been successfully performed following a one-pot strategy starting from alcohols, while the Henry reaction has been carried out following a sequential protocol for the first time. In both processes, enantiomerically enriched products were obtained with good yields and high enantioselectivities. We have also demonstrated that in reactions sensitive to small amounts of acid the use of alcohols instead of aldehydes could be a good solution for improving the results of these reactions.

One-Pot Synthesis of Cyclopropanes from Methylene Azabicyclo[3.1.0]hexanes Obtained by Formal Sequential [1+2]- and [2+3]-Cycloaddition Reaction of Prop-2-ynylsulfonium Salts and Tosylaminomethyl Enones


A formal sequential [1+2]- and [2+3]-annulation of prop-2-ynylsulfonium salts and tosylaminomethyl enones was developed, constructing a series of methylene azabicyclo[3.1.0]hexane derivatives. A one-pot procedure was established via hydration of an enamine intermediate to afford substituted cyclopropanes. Prop-2-ynylsulfonium salts acted as both C2 and C1 synthons in these two processes.

Reactivity and Synthetic Applications of α-Functionalized Oxime Acetates: Divergent Access to Fulleropyrrolidines and Mono- and Disubstituted 1-Fulleropyrrolines via Copper-Catalyzed Redox-Neutral N-Heteroannulation with [60]Fullerene


The unique reactivity and synthetic applications of oxime acetate derivatives with N, O and S-substituent at the α-position are disclosed for the first time, which leads to 2-substituted fulleropyrrolidines and mono- and disubstituted 1-fulleropyrrolines via copper-catalyzed redox-neutral N-heteroannulation reactions with C60. This transformation is operationally simple and has a broad substrate scope and good functional-group tolerance. Theoretical calculations at the level of B3LYP/6-31G(d) were performed to elucidate the chemoselectivity of the reaction.

Iodine Catalyzed Synthesis of Chalcogenophenes by the Reaction of 1,3-Dienyl Bromides and KSeCN/K2S


Abstract. Chalcogenophenes are of much importance in organic synthesis as well as in pharmaceutical industry. Thus synthesis of these molecules has received considerable interest. Although a number of methods are available many of them suffer from one or more of these drawbacks - harsh conditions, use of costly metals, general applicability, tedious purification process and low yield. To avoid these drawbacks a transition metal free iodine catalyzed reaction of aryl susbstituted 1,3-dienyl bromides with KSeCN/K2S leading to the corresponding selenophenes and thiophenes has been developed. Iodine is relatively benign, less expensive and readily available. A series of diversely substituted selenophenes and thiophenes have been obtained by this procedure in high yields. Using this procedure 2-(4-chlorophenyl)thiophene, a key intermediate for the synthesis of a melanin concentrating hormone receptor ligand involved in the treatment of eating disorders, weight gain, obesity, depression and anxiety has been synthesized. Although the reaction is one-pot essentially it proceeds in two steps involving a selenocyanate intermediate leading to selenophene. A possible mechanism for selenophene formation has been suggested. Similar mechanism is also suggested for thiophene formation via the intermediacy of potassium trans-1,3-dienyl thiolate. The simple operation, use of inexpensive reagent and a metal free process make this procedure more attractive for an easy access to substituted selenophenes and thiophenes.

Synthesis of diverse N-heterocycles via Pd-catalyzed tandem azide-isocyanide cross-coupling/cyclization: Mechanistic insight using experimental and theoretical studies


A rapid and elegant tandem azide-isocyanide cross-coupling/cyclization protocol is developed based on nitrene-transfer reaction. The Pd-catalyzed ligand-free methodology led to the synthesis of three different heterocyclic scaffolds with excellent atom/step/redox economy. Studies based on first-principles based quantum calculation and control experiments unraveled a concerted process of nitrene-transfer reaction on isocyanides, ruling out metalla-aziridine intermediate reported earlier. This finding would pave way for novel applications of nitrene-transfer reactions to generate bioactive heterocycles.

Catalytic Use of Low-Valent Cationic Gallium(I) Complexes as π-Acids


Transformations of alkene and alkyne substrates relevant to π-Lewis acid catalysis have been performed using low-valent Ga(I) species for the first time. [Ga(I)(PhF)2]+[Al(ORF)4] and gallium dichloride (i.e. [Ga(I)]+[GaCl4]) proved to be efficient catalysts for cycloisomerizations, Friedel-Crafts reactions, transfer hydrogenations, and reductive hydroarylations. Their activity is compared to more common Ga(III) complexes. This study shows that even the readily available and yet overlooked gallium dichloride salt can be a more active π-Lewis acid catalyst than gallium trichloride or other Ga(III) species.

Copper/Palladium-Catalyzed Cyclization/Cross-Coupling Cascade Reaction of 2-gem-Dibromovinyl Aryl Selenides: Synthesis of 2-Substituted Benzo[b]selenophenes


The copper/palladium-catalyzed multicomponent cyclization reactions, which combined 2-gem-dibromovinyl aryl selenides with a nucleophilic source, were applied to the synthesis of 2-substituted benzo[b]selenophenes. A systematic study of the cyclization system revealed that the mutual action between copper and palladium salts is essential for the formation of products in good yields, avoiding the formation of hydrogenated benzo[b]selenophenes. The versatility of 2-bromo-benzo[b]selenophenes was also studied by palladium- catalyzed reactions with boronic acid, Grignard reagent and methyl acrylate affording the cross-coupled products in good yields. In addition, the reaction of 2-bromo-benzo[b]selenophene towards halogen-lithium exchange reactions followed by the addition of aldehyde afforded the corresponding secondary alcohol.

Transition-metal-free Direct C3 Arylation of Quinoxalin-2(1H)ones with Arylamines under Mild Conditions


A transition-metal-free direct C3 arylation of quinoxalin-2(1H)-ones with arylamines has been explored. This reaction proceeded smoothly through radical reaction under mild conditions and produced the desired arylation products in good yields. The reactions proceeded efficiently over a broad range of substrates and functional group tolerance.

Directed C–H Alkenylation of Aryl Imines with Alkenyl Phosphates Promoted by a Cobalt–N-Heterocyclic Carbene Catalyst


We report herein an ortho-C–H alkenylation reaction of aryl imines with alkenyl phosphates promoted by a cobalt–N-heterocyclic carbene (NHC) catalytic system. While commercially available bulky NHC ligands exhibited only modest catalytic activity, elaboration of the N-substituents and the backbone of NHC enabled the desired transformation in high yield at a mild temperature. The new Co–NHC system proved applicable to a variety of aryl imines and alkenyl phosphates to afford ortho-alkenylated aryl imines, which serve as precursors to benzofulvene derivatives.

One-Pot Protocol for the Synthesis of Imidazoles and Quinoxalines using NBS


NBS-mediated one-pot green, efficient and practical synthesis of substituted imidazoles and quinoxalines has been reported by the reaction of styrenes with N-arylbenzamidines and o-phenylenediamines, respectively in water:1,4-dioxane mixture. The reaction involves formation of α-bromoketone as an intermediate in the presence of NBS and water, followed by condensation with N-arylbenzamidine and o-phenylenediamines. Use of an inexpensive NBS as a bromine source as well as an oxidant, water as a solvent and readily available starting materials make this protocol environmentally benign and economically viable. Substituted imidazoles and quinoxalines were obtained in good to excellent yields with wide functional group compatibility.

Effective Synthesis of Guanosine 5’-Diphospho-β-L-galactose Using Bacterial L-Fucokinase/Guanosine 5’-diphosphate-L-fucose Pyrophosphorylase


The nucleotide sugar guanosine 5’-diphospho-β-L-galactose (GDP-L-Gal) is known as a key intermediate of L-ascorbic acid biosynthesis pathway of plant and algae. In addition, GDP-L-Gal serves as a donor substrate of L-galactosyltransferase, which transfers L-Gal on the non-reducing ends of glycoconjugates. To synthesize varieties of L-Gal containing glycoconjugates and explore the novel L-galactosyltransferases, GDP-L-Gal needs to be prepared since it is not commercially available. In plants, GDP-D-mannose-3’,5’-epimerase (GME) converts GDP-α-D-mannose (GDP-D-Man) to GDP-L-Gal and GDP-L-gulose. GDP-L-Gal has been previously prepared using GME and GDP-D-Man, which equilibrium ratio was biased to GDP-D-Man. In this study, the efficient GDP-L-Gal production from L-Gal was established using bacterial L-fucokinase/GDP-L-fucose pyrophosphorylase (FKP), L-Fuc, adenosine 5’-triphosphate (ATP) and guanosine 5’-triphosphate (GTP). High synthesis yield was obtained after screening of the optimum FKP reaction conditions in a 96-well format and analysis by multiplexed capillary electrophoresis (MP-CE). Conversion of L-Gal substrate yielded 97% GDP-L-Gal using purified recombinant FKP expressed in E. coli Moreover, GDP-L-Gal was successfully purified with 92% (34.5 mg) overall yield from the FKP reaction mixture. GDP-L-Gal is now readily available for studies on L-galactosyltransferases and L-fucosyltransferases.

Metal-free radical-triggered selenosulfonation of 1,7-enynes for the rapid synthesis of 3,4-dihydroquinolin-2(1H)-ones in batch and flow


A novel three-component selenosulfonation of 1,7-enynes with sulfinic acids and diphenyl diselenides for the formation of multifunctional 3,4-dihydroquinolin-2(1H)-ones was developed in batch and flow. This room-temperature protocol provides a highly efficient approach to diverse selenosulfones in moderate to excellent yields and with a broad scope of substrates. It should provide a potential synthesis method for the construction of diverse and meaningful 3,4-dihydroquinolin-2(1H)-ones derivatives in the fields of pharmaceutical and biological chemistry. Additionally, obvious acceleration (20h to 43s) was obtained under micro flow conditions.

Recent Advances in the Synthesis of Aryl Nitrile Compounds


Aryl nitriles are found wide applications in natural products, pharmaceuticals, agrochemicals, dyes, and herbicides. Moreover, because the cyano group can be easily converted into various functional groups, aryl nitriles are important intermediates in synthetic organic chemistry. Consequently, the development of new methodologies for the synthesis of aryl nitriles is of significant interests. The traditional methods for their synthesis include Sandmeyer reactions, Rosenmund-von Braun reactions, dehydration reactions of aldoximes and amides. In recent years, numerous efforts have been devoted to the transition-metal-catalyzed cyanation reactions of aryl (pseudo)halides, organometallic reagents and aryl C-H bonds. A number of cyanating reagents have been explored for such transformations, including metal cyanides and organic cyano group sources. In addition, styrene and aryl-substituted alkynes are successfully converted into aryl nitriles through the C-C double or triple bond cleavage. Various benzylic compounds have also been reported for the synthesis of aryl nitriles, such as benzylic halides, alcohols, amines and azides. Furthermore, direct conversion of the methyl group of toluene derivatives into cyano group has also drawn attentions. In this critical review, we summarize the recent developments and useful applications in this field and their mechanisms are also briefly discussed.

2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)-Mediated C(sp2)-C(sp3) Cross-Dehydrogenative Coupling Reaction: α-Alkylation of Push-Pull Enamines and α-Oxo Ketene Dithioacetals


A novel metal-free cross-dehydrogenative coupling (CDC) reaction of C(sp2)-H of enamines and α-oxo ketene dithioacetals with C(sp3)-H of 1,3-diarylpropenes mediated by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone is reported. The α-alkylation products are obtained with moderate to good yields. The method provides an efficient and alternative strategy for the synthesis of the corresponding products.

The Palladium Acetate-Catalyzed Microwave-Assisted Hirao Reaction without an Added P-Ligand as a “Green” Protocol; A Quantum Chemical Study on the Mechanism


It was proved by our experiments that on microwave irradiation, the mono or bidentate P-ligands generally applied in the palladium(II)-catalyzed P–C coupling reaction of aryl bromides and dialkyl phosphites or secondary phosphine oxides may be substituted by the excess of the >P(O)H reagent that exists under a tautomeric equilibrium. Taking into account that the reduction of the palladium(II) salt and the ligation of the palladium(0) so formed requires 3 equivalents of the P species for the catalyst applied in a quantity of 5-10%, all together, 15–30% of the P-reagent is necessary beyond its stoichiometric quantity. In the coupling reaction of diphenylphosphine oxide, it was possible to apply diethyl phosphite as the reducing agent and as the P-ligand. The reactivity of the diethyl phosphite and diphenylphosphine oxide reagents was compared in a competitive reaction. The mechanism and the energetics of this new variation of the Hirao reaction of bromobenzene with Y2P(O)H reagents (Y=EtO and Ph) was explored by quantum chemical calculations. The first detailed study on simple reaction models justified our assumption that, under the conditions of the reaction, the trivalent form of the >P(O)H reagent may serve as the P-ligand in the palladium(0) catalyst, and shed light on the fine mechanism of the reaction sequence. Existence of the earlier described bis(palladium complex) {[H(OPh2P)2PdOAc]2} was refuted by high level theoretical calculations. This kind of complex may be formed only with chloride anions instead of the acetate anion. The interaction of palladium acetate and Y2P(O)H may result in only the formation of the [(HO)Y2P]2Pd complex that is the active catalyst in the Hirao reaction. The new variation of the Hirao reaction is of a more general value, and represents the greenest protocol, as there is no need for the usual P-ligands. Instead, the >P(O)H reagent should be used in an excess up to 30%. Hence, the costs and environmental burdens may be decreased.

Recent Advances in Palladium-Catalyzed Cross-Coupling Reactions at ppm to ppb Molar Catalyst Loadings


We review new developments in decreasing the catalyst loadings in palladium-catalyzed C–C bond-formation reactions to mol ppm or mol ppb levels. This decreases the cost of the catalyst and the toxicity of the reaction system, making the reaction more attractive to industry. The Heck reaction, Sonogashira reaction, Suzuki–Miyaura cross-coupling reaction, other cross-coupling reactions, and allylic arylation reactions are separately discussed to show clearly the progress made in each type of reaction. Apart from the catalyst loading, the other parameters of the reaction (temperature, solvent, etc.) are briefly discussed to illustrate the shift toward greener conditions. For most reactions, this shift is underway or well advanced, and catalyst loadings have been decreased to below 1 mol ppm. An abundance of catalytic systems are now available, and it is sometimes difficult to identify the best one, because the substrates examined can vary widely from publication to publication. In the future, emphasis should be placed on the studying the full scope of the reaction at mol ppm catalyst loadings, rather than examining a few examples at these levels during the reaction-optimization process.

One Pot Synthesis of γ-Benzopyranones via Iron-Catalyzed Aerobic Oxidation and Subsequent 4-Dimethylaminopyridine Catalyzed 6-endo Cyclization


One-pot synthesis of γ-benzopyranones was realized in decent yields and excellent regioselectivities via iron-catalyzed aerobic oxidation and 4-dimethylaminopyridine-catalyzed cyclization of related propargylic alcohols. Derivatizations to aromatic substituted γ-benzopyranones and synthesis of naturally occurring 3′,4′-dimethoxyflavone have also been realized.

Triflic Acid as an Efficient Brønsted Acid Promoter for the Umpolung of N-Ac Indoles in Hydroarylation Reactions


We report that triflic acid, a strong Brønsted acid, is a very powerful alternative to FeCl3 to mediate the hydroarylation of N−Ac indoles, which delivers regioselectively 3-arylindolines, 3,3-spiroindolines or 2-arylindolines. Mechanistic explorations point towards the existence of a highly electrophilic intermediate by simultaneous activation of the acetyl and of the C2=C3 bond by protons.

Organocatalytic Asymmetric Synthesis of Six-Membered Carbocycle-Based Spiro Compounds


Well-developed asymmetric organocatalysis has been widely incorporated in various cascade/tandem sequences, providing a simple access to structurally complex target molecules in a highly stereoselective fashion, including spirocyclic compounds. Among all types of spirocyclic skeletons, those containing a six-membered carbocyclic ring are recognized as an important core framework with up to six consecutive stereogenic centers and this motif is commonly found in many natural products, biologically active molecules and lead compounds. This review describes the asymmetric synthesis of spirocyclic compounds containing six-membered carbocycles using small organic molecules as catalysts.

Enzyme-Catalysed Synthesis of Cyclohex-2-en-1-one cis-Diols from Substituted Phenols, Anilines and Derived 4-Hydroxycyclohex-2-en-1-ones


Toluene dioxygenase-catalysed cis-dihydroxylations of substituted aniline and phenol substrates, with a Pseudomonas putida UV4 mutant strain and an Escherichia coli pCL-4t recombinant strain, yielded identical arene cis-dihydrodiols, which were isolated as the preferred cyclohex-2-en-1-one cis-diol tautomers. These cis-diol metabolites were predicted by preliminary molecular docking studies, of anilines and phenols, at the active site of toluene dioxygenase. Further biotransformations of cyclohex-2-en-1-one cis-diol and hydroquinone metabolites, using Pseudomonas putida UV4 whole cells, were found to yield 4-hydroxycyclohex-2-en-1-ones as a new type of phenol bioproduct. Multistep pathways, involving ene reductase- and carbonyl reductase-catalysed reactions, were proposed to account for the production of 4-hydroxycyclohex-2-en-1-one metabolites. Evidence for the phenol hydrate tautomers of 4-hydroxycyclohex-2-en-1-one metabolites was shown by formation of the corresponding trimethylsilyl ether derivatives.

Asymmetric Hydrolytic and Aminolytic Kinetic Resolution of Racemic Epoxides using Recyclable Macrocyclic Chiral Cobalt(III) Salen Complexes


New chiral macrocyclic cobalt(III) salen complexes were synthesized and used as catalyst for the asymmetric kinetic resolution (AKR) of terminal epoxides and glycidyl ethers with aromatic/aliphatic amines and water as nucleophiles. This is the first occasion where a Co(III) salen complex demonstrated its ability to catalyze AKR as well as hydrolytic kinetic resolution (HKR) reactions. Excellent enantiomeric excesses of the epoxides, the corresponding amino alcohols and diols (upto 99%) with quantitative yields were achieved by using the chiral Co(III) salen complexes in dichloromethane at room temperature. This protocol was further extended for the synthesis of two important drug molecules, i.e., (S)-propranolol and (R)-naftopidil. The catalytic system was also explored for the synthesis of chirally pure diols and chiral cyclic carbonates using carbon dioxide as a greener renewable C1 source. The catalyst was recycled for upto 5 catalytic cycles with retention of enantioselectivity.

Photocatalytic Oxidative Bromination of Electron-Rich Arenes and Heteroarenes by Anthraquinone


The estimated excited oxidation potential of sodium anthraquinone-2-sulfonate (SAS) increases from 1.8 V to about 2.3 V vs SCE by protonation with Brønsted acids. This increased photooxidation power of protonated anthraquinone was used for the regio-selective oxidative bromination of electron rich (hetero)arenes and drugs in good yield. The mild reaction conditions are compatible with many functional groups, such as double and triple bonds, ketones, amides and amines, hydroxyl groups, carboxylic acids and carbamates. Mechanistic investigations indicate the photooxidation of the arene followed by nucleophilic bromide addition as the likely pathway.

Three-Component Coupling Reactions of Maleimides, Thiols, and Amines: One-Step Construction of 3,4-Heteroatom-functionalized Maleimides by Copper-Catalyzed C(sp2)−H Thioamination


A copper-catalyzed intermolecular thioamination of maleimides with thiols and amines has been developed. A diverse range of 3-amino-4-thiomaleimides and 3,4-dihydropyrrolo[3,4-b][1,4]thiazine-5,7(2H,6H)-diones were obtained with good yields, involving C−N and C−S bond formations. This methodology is very practical and features high atom economy, excellent functional group tolerance.

An Unexpected Domino Reaction of β-Keto Sulfones with Acetylene Ketones Promoted by Base: Facile Synthesis of 3(2H)-Furanones and Sulfonylbenzenes


An unexpected domino reaction of β-keto sulfones with acetylene ketones has been developed. The domino reaction of β-keto sulfones with diynones proceeded smoothly in the presence of 30 mol% K2CO3 without other additives, and afforded the novel 3(2H)-furanone derivatives. On replacing the diynones with terminal alkyne ketones, the reaction regioselectivity was changed and sulfonylbenzenes were obtained via benzannulation in good yields.

Asymmetric 1,6-Conjugate Addition of para-Quinone Methides for the Synthesis of Chiral β,β-Diaryl-α-Hydroxy Ketones


A direct asymmetric 1,6-conjugated addition of α-hydroxy ketone to para-quinone methides has been developed. It is an efficient approach to the synthesis of chiral β,β-diaryl-α-hydroxy ketones. The reaction runs smoothly in the presence of ZnEt2 and nonracemic bis(diarylhydroxymethylpyrrolidinylmethyl)phenols (ProPhenols), and the desired products are obtained in good yields (up to 88%) and with high stereoselectivity (up to >99% ee and up to >99:1 dr). This reaction also can be run on a gram scale without impacting its enantioselectivity.

Iodine/Copper(I)-Catalyzed Direct Annulation of N-Benzimidazolyl Amidines with Aldehydes for the Synthesis of Ortho-Fused 1,3,5-Triazines


A direct annulation reaction of N-benzimidazolyl amidines with aldehydes has been established and allows the synthesis of ortho-fused 1,3,5-triazine derivatives. The N-benzimidazolyl amidine substrates are readily accessible by the addition of 2-aminobenzimidazoles to the corresponding nitriles. In the presence of molecular iodine and copper iodide, cyclization of benzimidazolyl amidines with various aldehydes in toluene under reflux followed by oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) gives the corresponding products. In this reaction, iodine acts more as a Lewis acid catalyst than as an oxidant. This synthetic process is insensitive to air and operationally simple, and provides facile access to a variety of novel 1,3,5-triazino[1,2-a]benzimidazoles and related heterocycles.

Recent Progress in Organocatalytic Asymmetric Domino Transformations


Sustainability in chemical synthesis is a major aspect of the current synthetic endeavors and, therefore, mimicking the biological process in the laboratory nowadays has the highest priority. Towards achieving this goal, designing organic reactions in domino mode rather than the multistep synthetic pathways and using organocatalysis instead of metal catalysis have received a lot of attention due to the inherent advantages of these processes in terms of synthetic efficiency and sustainability. As a result, the field of asymmetric organocatalytic domino reactions has witnessed tremendous progress in recent years. This review attempts to summarize the latest developments in asymmetric organocatalyzed domino reactions since 2012, with the emphasis on the catalysts and reaction modes. Discussions on the reaction mechanisms and the applications of the developed domino reaction methods in the synthesis of biologically active molecules and natural products are also included when appropriate.

Intermolecular Tandem Addition/Esterification Reaction of Alkenes with Malonates Leading to γ-Lactones Mediated by Molecular Iodine under Visible Light Irradiation


The front cover picture provided by Saki Maejima, Eiji Yamaguchi, and Akichika Itoh, depicts the utility of inexpensive molecular iodine as the mediator for the straightforward synthesis of lactones. Visible light irradiation to molecular iodine generates iodine radicals which could mediate a C−C/C−O bond-forming reaction of olefins with carbonyl compounds furnishing polyfunctionalized γ-butyrolactones. The study offers an interesting way of utilizing visible light and iodine radicals for intermolecular C–C bond-forming transformations. Details can be found in the communication on pages XXXX–XXXX (S. Maejima, E. Yamaguchi, A. Itoh, Adv. Synth. Catal. 2017, 359, XXXX–XXXX; DOI 10.1002/adsc.201700809).

Copper-Catalyzed Cascade Cyclization of 2-Propynolphenols: Access to 4-Phosphorylated 2H-Chromenes


A novel copper-catalyzed cascade cyclization of easily prepared 2-propynolphenols with disubstituted phosphine oxides has been developed to give 4-phosphorylated 2H-chromenes in moderate to excellent yields. This cascade process involves multiple bond-forming events including C–O and C–P bonds. Moreover, both tertiary and secondary propargylic alcohols with diverse functional groups showed excellent compatibilities under ligand- and additive-free conditions.

Chemo-Enzymatic Synthesis of Branched N-Acetyllactosamine Glycan Oligomers for Galectin-3 Inhibition


We present here a novel concept for the synthesis of branched N-acetyllactosamine (LacNAc) glycan structures. Through a combination of sequential enzymatic and chemical reactions of Leloir-glycosyltransferases, galactose oxidase and reductive amination, we obtained branched glycan oligomers with a variation of LacNAc and/or N′,N′′-diacetyllactosamine (LacdiNAc) glycan epitopes. Incorporation of a branching point was accomplished by an optimized galactose oxidase protocol rendering the C-6 aldehyde functionality at the terminal galactose of a LacNAc oligomer. After glycan chain elongation by glycosyltransferases, the C-6 aldehyde-containing linear building block was conjugated with amine-linker functionalized glycans. Methanol and a temperature of 50 °C were found to be optimum conditions for the α-picoline borane-catalyzed reductive amination. Chemically branched glycans were obtained in high synthetic yields (≈81%) in preparative batches. Product isolation was accomplished by preparative HPLC with good overall yields (>60%). The structural integrity was proven by ESI-MS and NMR. The herein synthesized branched LacNAc oligomers feature a variation of Lac(di)NAc epitopes and were confirmed to be potent inhibitors of human galectin-3 (Gal-3). The branched decasaccharide with two LacdiNAc-LacNAc branches ranks among the most potent poly-LacNAc-based Gal-3 inhibitors so far.

One-Pot Enantioselective Synthesis of d-Phenylglycines from Racemic Mandelic Acids, Styrenes, or Biobased l-Phenylalanine via Cascade Biocatalysis


Enantiopure d-phenylglycine and its derivatives are an important group of chiral amino acids with broad applications in thepharmaceutical industry. However, the existing synthetic methods for d-phenylglycine mainly rely on toxic cyanide chemistry and multistep processes. To provide green and safe alternatives, we envisaged cascade biocatalysis for the one-pot synthesis of d-phenylglycine from racemic mandelic acid, styrene, and biobased l-phenylalanine, respectively. Recombinant Escherichia coli (LZ110) was engineered to coexpress four enzymes to catalyze a 3-step reaction in one pot, transforming mandelic acid (210 mM) to give enantiopure d-phenylglycine in 29.5 g L−1 (195 mM) with 93% conversion. Using the same whole-cell catalyst, twelve other d-phenylglycine derivatives were also produced from the corresponding mandelic acid derivatives in high conversion (58–94%) and very high ee (93–99%). E. coli (LZ116) expressing seven enzymes was constructed for the transformation of styrene to enantiopure d-phenylglycine in 80% conversion via a one-pot 6-step cascade biotransformation. Twelve substituted d-phenylglycines were also produced from the corresponding styrene derivatives in high conversion (45–90%) and very high ee (92–99%) via the same cascade reactions. A nine-enzymeexpressing E. coli (LZ143) was engineered to transform biobased l-phenylalanine to enantiopure d-phenylglycine in 83% conversion via a one-pot 8-step transformation. Preparative biotransformations were also demonstrated. The high-yielding synthetic methods use cheap and green reagents (ammonia, glucose, and/or oxygen), and E. coli whole-cell catalysts, thus providing green and useful alternative methods for manufacturing d-phenylglycine.

A Deoxygenative [4+1] Annulation Involving N-Acyldiazenes for an Efficient Synthesis of 2,2,5-Trisubstituted 1,3,4-Oxadiazole Derivatives


An unprecedented and highly efficient tris(dimethylamino)phosphine [P(NMe2)3]-mediated deoxygenative [4 + 1] annulation of N-acyldiazenes with α-dicarbonyl compounds such as isatins, α-keto esters, and α-diketones is reported. The annulation reactions proceed smoothly under mild conditions to deliver a broad range of 2,2,5-trisubstituted 1,3,4-oxadiazole derivatives in moderate to excellent yields from readily available starting materials. It represents the first realization of the [4+1] annulation mode involving N-acyldiazenes to construct five-membered heterocycles.

Efficient Heterogeneous Gold(I)-Catalyzed Direct C(sp2)–C(sp) Bond Functionalization of Arylalkynes through a Nitrogenation Process to Amides


The first heterogeneous gold(I)-catalyzed direct C(sp2)–C(sp) bond functionalization of arylalkynes through a nitrogenation process to amides has been achieved by using an ordered mesoporous silica (MCM-41)-immobilized phosphine gold(I) complex [MCM-41-PPh3-AuCl] as catalyst and silver carbonate (Ag2CO3) as cocatalyst with trimethylsilyl azide (TMSN3) as a nitrogen source, yielding a variety of amides in moderate to excellent yields under mild conditions. This heterogeneous phosphine gold(I) complex shows the same turnover numbers as the homogeneous chloro(triphenylphosphine)gold(I) (Ph3PAuCl) and can easily be recovered by simple filtration of the reaction solution and recycled at least eight times without significant loss of activity, providing a novel, efficient, practical and economic method for the synthesis of amides from alkynes.

Regioselective Synthesis of Selenide Ethers through a Decarboxylative Coupling Reaction


An efficient and selective approach to the synthesis of selenide ethers containing one or two geminal C–Se bonds from readily available diselenides and phenylacetic acids was developed. Compounds containing one C–Se bond were prepared by employing air as the oxidant under metal-free conditions, whereas compounds having two geminal C–Se bonds were formed via the iron(III) chloride/oxygen/cesium carbonate (FeCl3/O2/Cs2CO3) system. Moreover, 1,2-diphenyldisulfane also could be smoothly converted into the corresponding sulfur ether product under the standard reaction conditions.

Highly Regio- and Enantioselective Nitroso Diels−Alder Reaction of 1,3-Diene-1-carbamates Catalyzed by Chiral N,N′-Dioxide/Copper(II) Complex


A chiral N,N′-dioxide/Copper(II) complex-catalyzed highly regio- and enantioselective nitroso Diels−Alder (NDA) reaction of 2-nitrosopyridines with 1,3-diene-1-carbamates was described. A series of 3,6-dihydro-1,2-oxazines were obtained in good to excellent yields and ee values. On the basis of the control experiments, ESI-MS analysis and the absolute configuration of the product, a possible transition state model was proposed to explain the stereocontrol.

Regioselective Epoxidations by Cytochrome P450 3A4 Using a Theobromine Chemical Auxiliary to Predictably Produce N-Protected β- or γ-Amino Epoxides


N-Protected β- and γ-amino epoxides are useful chiral synthons. We report here that the enzyme cytochrome P450 3A4 can catalyze the formation of such compounds in a regio- and stereoselective manner, even in the presence of multiple double bonds or aromatic substituents. To this end, the theobromine chemical auxiliary is used not only to control the selectivity of the enzyme, but also as a masked amine, and to facilitate product recovery. Theobromine predictably directed epoxidation at the double bond of the fourth carbon from the theobromine group. Unlike with most catalysts, the selectivity did not depend on electronic or steric factors but rather on the position of the olefin relative to the theobromine group.

A Structure-Based Activity Study of Highly Active Unsymmetrically Substituted NHC Gold(I) Catalysts


Following the modular template synthesis using isonitriles, new unsymmetrically substituted five-membered saturated N-heterocyclic carbene (NHC) and N-heterocyclic oxo-carbene (NHOC) gold(I) complexes were prepared. With these species and already reported complexes, a detailed study concerning the catalytic activities of the complex classes available by the isonitrile route was conducted. The catalytic properties of twelve different types of NHOCs, saturated and unsaturated NHC gold(I) pre-catalysts with different substituents, as well as one representative of a six-membered NHC and one N-acyclic carbene (NAC) gold(I) complex were analyzed by utilizing the phenol synthesis as a test reaction. For this reaction, the saturated NHC gold(I) complexes achieved higher conversions than the corresponding unsaturated NHCs and the NHOC systems. While unsaturated NHC complexes show higher catalytic activity during the initial phase of the conversion, due to a higher stability, higher turnover numbers (TONs) were obtained for the corresponding saturated systems. A cyclopentadecyl substituent at nitrogen turned out to be the privileged substituent for all of the unsymmetrical complexes. Furthermore, we detected that light exclusion can significantly increase the catalytic activity of NHC gold(I) complexes for phenol synthesis.

One-Pot Synthesis of N-Alkyl Benzotriazoles via a Brønsted Acid-Catalyzed Three-Component Reaction


A novel three-component condensation reaction of benzotriazoles, aldehydes and tertiary anilines efficiently catalyzed by readily available organic acid p-toluenesulfonic acid (PTSA) has been developed. A series of N-alkyl benzotriazoles were synthesized in up to 97% yield for 21 examples starting from anilines, benzotriazoles and formaldehyde. This strategy features a simple system, atom economy, environmental friendliness, high efficiency, excellent regioselectivity, good functional group tolerance, easily available starting materials, and cheap catalyst. The mechanistic studies indicated that aza quinone methide was probably involved as an intermediate in this transformation.

Palladium-Catalyzed Cross-Coupling/Annulation Cascade for Synthesis of 9-Hydroxy and 9-Aminofluorenes.


9-Hydroxyfluorenes are easily synthesized via a tandem Suzuki/phenolic aldolisation sequence. This process was extended to 9-aminofluorenes by simply adding various amines as third partners. X-ray structures and NMR studies confirmed the presence of intermolecular O−H ⋅ ⋅ ⋅ N hydrogen bonding.

Ester Synthesis in Water: Mycobacterium smegmatis Acyl Transferase for Kinetic Resolutions


The acyl transferase from Mycobacterium smegmatis (MsAcT) catalyses transesterification reactions in aqueous media because of its hydrophobic active site. Aliphatic cyanohydrin and alkyne esters can be synthesised in water with excellent and strikingly opposite enantioselectivity [(R);E>37 and (S);E>100, respectively]. When using this enzyme, the undesired hydrolysis of the acyl donor is an important factor to take into account. Finally, the choice of acyl donor can significantly influence the obtained enantiomeric excesses.

Iodobenzene Dichloride/Zinc Chloride-Mediated Synthesis of N-Alkoxyindole-3-carbonitriles from 3-Alkoxyimino-2-arylalkylnitriles via Intramolecular Heterocyclization


A series of N-alkoxyindole-3-carbonitriles were synthesized, under mild conditions, via intramolecular heterocyclization of the readily available 3-alkoxyimino-2-arylalkylnitriles mediated by iodobenzene dichloride/zinc chloride. The mechanism of the reaction proposes the formation of a key intermediate of nitrenium cation from a chlorination and dechlorination process facilitated by the hypervalent iodine reagent and Lewis acid respectively.

Recent Advances in C–B Bond Formation through a Free Radical Pathway


The development of a methodology for the preparation of arylboronic acids or arylboronates is of significant interest to organic chemists. Classical synthetic methods to prepare these organoboron compounds are based on the reaction of Grignard or lithium reagents with trialkyl borates. In the past few decades, the transition- metal-catalyzed borylation of aryl halides, or pseudohalides, and C–H bonds of hydrocarbons has been a powerful tool for the synthesis of arylboronates in modern organic synthesis. These transformations are generally considered to proceed via organometallic intermediates generated by oxidative addition or transmetalation processes from the boron reagent. Several reviews on this type of borylation catalyzed by transition metals have been published in the literature. Interestingly, there has been a novel recognition that the boron reagent can participate in free-radical coupling via the homolytic cleavage of the boron-boron bond in recent years. In this review, recent advances in this new area of boron chemistry are summarized and the reaction mechanisms are also discussed.

Cobalt-Catalyzed Diastereoselective [4+2] Annulation of Phosphinamides with Heterobicyclic Alkenes at Room Temperature


Cobalt-catalyzed sp2 C−H bond functionalization of diarylphosphinamides with heterobicyclic alkenes was demonstrated at room temperature employing commercially available cobalt(II)-salts. The effectiveness of this strategy was illustrated with the reaction of various 8-aminoquinoline derived phosphinic amides and 7-oxa/azabenzonorbornadienes. The reaction conditions exhibited excellent functional group tolerance and high diastereoselectivities. Furthermore, extension of this approach to the preparation of polyaryl cyclic phosphinamides was achieved through the dehydrative ring opening/aromatization sequence.

FeCl3–Catalyzed Cascade Reactions of Cyclic Amines with 2-Oxo-2-arylacetic Acids toward Furan-2(5H)-one Fused N,O-Bicyclic Compounds


A novel and efficient synthesis of furan-2(5H)-one fused N,O-containing bicyclic compounds via the cascade reactions of N-aryl substituted cyclic amines with 2-oxo-2-arylacetic acids is presented. Mechanistically, the formation of the title compounds is initiated by the in situ formation of a cyclic enamine intermediate via FeCl3/di-tert-butyl peroxide (TBP)/oxygen (O2)-promoted C(sp3)−H dehydrogenation of saturated cyclic amine. Nucleophilic addition of the cyclic enamine intermediate onto 2-oxo-2-arylacetic acid followed by cyclization and dehydration gives the bicyclic heterocycle products. This intermolecular oxidative annulation constitutes an extension of tertiary amine-based Mannich-type β-functionalization leading to a series of N,O-bycyclic compounds in good yields with ease.

Visible light induced Trifluoromethyl Migration: Easy Access to α-Trifluoromethylated Ketones from Enol Triflates


Herein, we reported a novel method to synthesize α-trifluoromethylated ketones from enol triflates. Involving a cascade sulfur dioxide extrusion and a CF3 (trifluoromethyl) radical addition process, this reaction proceeds at room temperature and is driven by visible light irradiation. This protocol bears good functional group compatibility, which can generate the desired products in good to excellent yields even in gram scale. It is hoped that this approach to generate CF3 radicals from enol triflates can be used in other radical-involved reactions.

Selective Oxidative Coupling Reaction of Isocyanides Using Peroxide as Switchable Alkylating and Alkoxylating Reagent


A switchable oxidative coupling reaction of isocyanide and peroxide has been disclosed. In the presence of iron catalyst, the coupling reaction affords N-arylacetamides in good yields. By simply replacing the iron with copper catalyst, another different coupling reaction takes place in which peroxide can serve as alkoxylating source. This protocol represents a new fundamental coupling of two basic chemicals involving C−C and C−O bond-forming process. The unusual reactivity of an isocyano group in a radical reaction acting formally as an amidoyl synthon has also been well established. The experiment outcome reveals that aromatic isocyanides are particularly compatible reaction partners in present coupling reaction, whereas no desired products are observed when aliphatic isocyanides are used.

Iridium(III)-Catalyzed Selective and Mild C-H Amidation of Cyclic N-Sulfonyl Ketimines with Organic Azides


A general protocol for iridium catalyzed direct C−H amidation of cyclic N-sulfonyl ketimines using sulfonyl, acyl and aryl azides as nitrogen source is reported herein. The reaction takes place at room temperature with acyl and aryl azides, while an elevated temperature needed with sulfonyl azides to furnish aminated sultams in excellent yields with complete chemo and regioselectivity, thus providing a robust and environmentally benign process to the synthesis of aminosultams.

Palladium-Catalyzed Three-Component Tandem Reaction for One-pot Highly Stereoselective Synthesis of (Z)-α-Hydroxymethyl Allylic Sulfones


A novel method is reported for the stereoselective synthesis of highly functionalized allyl aryl sulfones. This protocol is based on a Pd-catalyzed three-component tandem reaction of sulfonyl hydrazides and aryl iodides with allenes and exhibits high (Z)-selectivity, good yields, minimal waste, ample product scope, and operational simplicity.

An Efficient Metal-Free Method for the Denitrosation of Aryl N-Nitrosamines at Room Temperature


A simple and practical method for the denitrosation of aryl N-nitrosamines to secondary amines is reported under metal-free conditions using iodine and triethylsilane. Several reduction-susceptible functional groups such as alkene, alkyne, nitrile, nitro, aldehyde, ketone and ester were found to be very stable during the denitrosation, which is remarkable. Broad substrate scope, room temperature reactions and excellent yields are the additional features of the current methodology.

Visible Light-Promoted Synthesis of Spiroepoxy Chromanone Derivatives via a Tandem Oxidation/Radical Cyclization/Epoxidation Process


The inside cover picture, provided by Sungwoo Hong and co-workers, illustrates a highly efficient and straightforward approach for the synthesis of spiroepoxy chroman-4-one derivatives with light irradiation using a blue LED under mild reaction conditions. During the reaction, the aldehyde generated in situ from the benzyl alcohol could further undergo visible light-mediated internal radical cyclization and epoxidation, allowing the rapid generation of valuable and synthetically useful spiroepoxy chroman-4-ones and their nitrogen-containing derivatives. Details of this work can be found in the communication on pages xxxx–xxxx (S. Jung, J. Kim, S. Hong, Adv. Synth. Catal. 2017, 359, xxxx–xxxx; DOI: 10.1002/adsc.201701072).

Asymmetric Construction of Spiropyrazolone Skeletons via Amine-Catalyzed [3+3] Annulation


Here we report a secondary amine-catalyzed, highly enantioselective [3+3] cyclization reaction of α-alkylidene pyrazolinones and α,β-unsaturated aldehydes, which facilely delivers a variety of enantioenriched spiropyrazolones showing structural and stereochemical complexity. The reaction uses an iminium ion activation strategy to activate both the β- and ipso-positions of the enals as dielectrophilic sites. A broad range of substrates are compatible with this mild reaction system.

Cadmium(II) Chloride-Catalyzed Dehydrative C−P Coupling of Propargyl Alcohols with Diarylphosphine Oxides to Afford Allenylphosphine Oxides


The cadmium(II) chloride-catalyzed dehydrative C−P cross-coupling reaction of propargyl alcohols with diarylphosphine oxides is reported. Several propargyl alcohols including those bearing the sterically demanding tert-butyl group at the triple bond terminus can be used as good substrates in the reaction to produce the corresponding allenylphosphine oxides in good to high yields in acetonitrile at 100 °C. The reaction can also be easily scaled up to a gram-scale synthesis. A mechanism study indicates that the reaction may proceed through a process of propargylic substitution to generate phosphonite intermediates followed by [2,3] sigmatropic rearrangement to produce the allenyl products, rather than through a common allenylative substitution resulting from P-nucleophilicity.

Synergistic Cooperative Effect of Sodium borohydride-Iodine Towards Cascade C−N and C−S/Se Bond Formation: One-pot Regioselective Synthesis of 3-Sulfenyl/selenyl Indoles and Mechanistic Insight


In this work, a new strategy to synthesize 3-sulfenyl/selenyl indole is reported wherein LC−MS reveals a novel insight into synergistic cooperative effect of NaBH4-I2 which allows cascade C−N and C−S/C−Se bond formations via reduction-nucleophilic cyclization-chalcogenylation, three steps in one-pot, towards regioselective synthesis of diverse 3-chalcogenyl indoles including 5-bromo-3-[(3,4,5-trimethoxyphenyl)thio]-1H-indole, a known lead anticancer compound, directly from 2-amino-phenacylchlorides and thiophenols or disulfides/diselenides in aqueous dioxane under transition-metal-free condition.

Palladium-Catalyzed Ring-Opening of 2-Alkylidenecyclobutanols: Stereoselective Synthesis of γ,δ-Unsaturated Ketones by C−C Bond Cleavage


A facile synthesis of γ,δ-unsaturated ketones via palladium-catalyzed ring-opening of 2-alkylidenecyclobutanols with organic halides is described. The key step involves Csp3 −Csp2 bond cleavage via palladium-catalyzed β-carbon elimination. The desired γ,δ-unsaturated ketones are obtained in good to excellent yields and broad functional group tolerability. Aryl, heteroaryl, benzyl, and alkynyl halides all readily participate to forge tri-substituted carbon-carbon double bond in a stereoselective manner.

Vinylogous Nucleophiles Bearing the Endocyclic Double Bond in the Allylic Alkylation with Morita-Baylis-Hillman Carbonates


This study demonstrates that vinylogous transfer of nucleophilicity in the allylic alkylation with Morita-Baylis-Hillman carbonates can be accomplished through the endocyclic double bond in 3-cyano-4-methylcoumarins. The developed reaction provides a straightforward access to functionalized coumarin derivatives of biological and synthetic relevance. Target, highly functionalized products have been chemoselectively and efficiently obtained in very high yield (up to 98%) and with excellent enantioselectivity (up to 99.5:0.5 er).

Asymmetric Dearomative Halogenation of β-Naphthols: The Axial Chirality Transfer Reaction


Axial naphthols are applied in asymmetric halogenative dearomatization reactions under simple and mild conditions in the work presented herein. The axial-to-central chirality conversion is efficiently accomplished, and the desired halogenated dearomatization products are obtained in high yields and enantioselectivities. By using commercially available halogenation reagents, the asymmetric fluorinative, chlorinative and brominative dearomatization reactions of axial naphthols derived from BINOLs are achieved. (BINOL=1,1′-Bi-2-naphthol)

Rhodium-Catalyzed C−H Functionalization of Indoles with Diazo Compounds: Synthesis of Structurally Diverse 2,3-Fused Indoles


A Rhodium-catalyzed C2-H functionalization of indoles with diazo compounds, followed by intramolecular nucleophilic addition to C=O or C=C bonds, is reported for divergent synthesis of 2,3-fused indoles. Besides acceptor/acceptor diazo compounds, donor/acceptor diazo compounds are broadly tolerated, giving various 2,3-fused indoles with perfect diastereocontrol. Notably, a selective C−H dialkylation reaction at C2 and C7 position of indoles has also been developed by simply changing the reaction conditions. This environmentally benign transformation proceeds under mild conditions and gives dinitrogen as the only by-product.

Decarboxylative Synthesis of Functionalized Oxindoles via An Iron-Initiated Radical Chain Process and Application in Constructing Diverse Fused-Indoline Heterocycles


Rapid construction of diverse fused-indoline−heterocycle (FIH) frameworks including high-value pyrroloindolines, furoindolines and thienoindolines in a two-step sequence has been described. The key to success hinges on the adoption of peresters as α-heteroatom alkyl radical precusors, which can smoothly react with N-arylacrylamides via a radical chain process initiated by inexpensive FeCl2⋅4H2O to afford the functionalized oxindoles, the key intermediates to FIH skeletons. The approach features operationally-simplicity, broad substrates scope and mild conditions.

Three-Component Thieno[2,3-b]indole Synthesis from Indoles, Alkenes or Alkynes and Sulfur Powder under Metal-Free Conditions


A Bronsted acid promoted three-component synthesis of substituted thieno[2,3-b]indole has been developed starting from indoles, alkenes or alkynes, and sulfur powder. N,N-Dimethylformamide plays an important role to convert the starting materials into the fused products. Various functional groups attached to substrates were well tolerated to afford the corresponding products in moderate to good yields under very simple reaction conditions.