Synthesis of Isoxazol-5(2H)-one Derivatives via (tBuO)2Mg Promoted [3 + 2] Annulations of δ-Acetoxy Allenoates with Hydroxylamine.

Herein, an efficient (tBuO)2Mg promoted [3 + 2] annulation of δ-acetoxy allenoates with N-benzylhydroxylamine has been developed. This method provides a concise and facile protocol to synthesize vinylated isoxazol-5(2H)-one derivatives stereospecifically in a broad substrate scope with high efficiency (31 examples, up to 87% yield).

Synthesis of tetracyclic dibenzo[b,f][1,4]oxazepine-fused ß-lactams via visible-light-induced Staudinger annulation.

An efficient visible-light-induced Staudinger [2 + 2] annulation reaction between α-diazo ketones and dibenzo[b,f][1,4]oxazepine/thiazepine-imines under catalyst-free conditions has been developed. This protocol provides a facile method to synthesize tetracyclic dibenzo[b,f][1,4]oxazepine/thiazepine-fused ß-lactams bearing a quaternary carbon center with a broad substrate scope and high efficiency (37 examples, up to >99% yield).

NHC-catalyzed formal [3 + 3] annulations of δ-acetoxy allenoates for the synthesis of 4H-pyran derivatives.

Herein, an N-heterocyclic carbene (NHC) catalyzed formal [3 + 3] annulation of δ-acetoxy allenoates with 1C,3O-bisnucleophiles for the construction of 4H-(fused)pyrans has been developed. This protocol provides a facile method to synthesize highly functionalized 4H-pyrans and has a broad substrate scope (30 examples, up to 77% yield).

Copper-catalyzed [3+2] annulation of O-acyl ketoximes with 2-aryl malonates for the synthesis of 3-aryl-4-pyrrolin-2-ones.

A copper-catalyzed [3+2] annulation of O-acyl ketoximes with 2-aryl malonates for the concise synthesis of 3-aryl-4-pyrrolin-2-ones has been developed. The advantage of this method lies in the use of O-acyl oximes as an internal oxidant to generate the nucleophilic enamines and electrophilic p-quinone methides concurrently. The subsequent nucleophilic addition undergoes selectively on the α-C of malonates.

Synthesis of ß-Ketonitriles via N-Heterocyclic-Carbene-Catalyzed Radical Coupling of Aldehydes and Azobis(isobutyronitrile).

Herein, an NHC (N-heterocyclic carbene)-catalyzed radical coupling reaction between aldehydes and azobis(isobutyronitrile) (AIBN) has been developed. This method provides an efficient and convenient approach for the synthesis of ß-ketonitriles containing a quaternary carbon center (31 examples, up to >99% yield) utilizing commercially available substrates. This protocol features broad substrate scope, good functional group tolerance, and high efficiency under metal-free and mild reaction conditions.

Stereoselective synthesis of C3-tetrasubstituted oxindoles via copper catalyzed asymmetric propargylation.

Herein, a copper catalyzed asymmetric propargylation of 2-oxindole-3-carboxylate esters with terminal propargylic esters is described. This strategy successfully provides a direct approach to constructing a broad range of chiral C3-tetrasubstituted oxindoles with contiguous tertiary and quaternary carbon stereocenters in high yields and excellent enantioselectivities (16 examples, up to 99% yield and 98% ee). Moreover, the diastereoisomers of the two newly formed stereocenters can be separated by silica gel chromatography, thereby providing a valuable stereoselective access to all four possible stereoisomers of C3-tetrasubstituted oxindoles.

NHC-Catalyzed [2 + 4] Annulation of Alkynyl Ester with Chalcone.

An NHC-catalyzed [2 + 4] cyclization of alkynyl ester with α,ß-unsaturated ketone to form a pyran scaffold was developed successfully. The cheap and easily available starting materials, mild reaction conditions, moderate to excellent yields, and high atom economy make this strategy attractive for the syntheses of highly substituted 4H-pyran derivatives.

NHC-catalyzed [4 + 2] annulations of allenoates and 2,3-dioxopyrrolidine derivatives.

A facile NHC-catalyzed [2 + 4] annulation of allenoates with 2,3-dioxypyrrolidine derivatives was discovered, which paved a new avenue for the construction of highly substituted pyranopyrrole with moderate to good yields, high atom economy and mild reaction conditions.

Copper-Catalyzed Bisannulations of Malonate-Tethered O-Acyl Oximes with Pyridine, Pyrazine, Pyridazine, and Quinoline Derivatives for the Construction of Dihydroindolizine-Fused Pyrrolidinones and Analogues.

A copper-catalyzed bisannulation reaction of malonate-tethered O-acyl oximes with pyridine, pyrazine, pyridazine, and quinoline derivatives has been developed for the concise synthesis of structurally novel dihydroindolizine-fused pyrrolidinones and their analogues. The present reaction shows excellent regioselectivity and stereoselectivity. Theoretical calculations reveal that the coordination effect of the carbonyl group in the nucleophilic substrate determines the excellent regioselectivity. Further functionalization of the generated dihydroindolizine-fused pyrrolidinone could be easily realized through substitution, Michael addition, selective aminolysis, and hydrolysis reactions.

Pd(II)-Catalyzed Arylation/Oxidation of Benzylic C-H of 8-Methylquinolines: Access to 8-Benzoylquinolines.

An efficient access to 8-benzoylquinoline was developed by a sequential arylation/oxidation of 8-methylquinolines with aryl iodides in the presence of Pd(OAc)2. This transformation demonstrates good tolerance of a wide range of functional groups on aryl iodides, providing good to excellent yields of 8-benzoylquinolines.

Enzymological characterization of a novel d-lactate dehydrogenase from Lactobacillus rossiae and its application in d-phenyllactic acid synthesis.

A novel lactate dehydrogenase gene, named lrldh, was cloned from Lactobacillus rossiae and heterologously expressed in Escherichia coli. The lactate dehydrogenase LrLDH is NADH-dependent with a molecular weight of approximately 39 kDa. It is active at 40 °C and pH 6.5 and stable in a neutral to alkaline environment below 35 °C. The kinetic constants, including maximal reaction rate (V max), apparent Michaelis-Menten constant (K m), turnover number (K cat) and catalytic efficiency (K cat/K m) for phenylpyruvic acid were 1.95 U mg-1, 2.83 mM, 12.29 s-1, and 4.34 mM-1 s-1, respectively. Using whole cells of recombinant E. coli/pET28a-lrldh, without coexpression of a cofactor regeneration system, 20.5 g l-1 d-phenyllactic acid with ee above 99% was produced from phenylpyruvic acid in a fed-batch biotransformation process, with a productivity of 49.2 g l-1 d-1. Moreover, LrLDH has broad substrate specificity to a range of ketones, keto acids and ketonic esters. Taken together, LrLDH is a promising biocatalyst for the efficient synthesis of d-phenyllactic acid and other fine chemicals.

Base-promoted regiodivergent allylation of N-acylhydrazones with Morita-Baylis-Hillman carbonates by tuning the catalyst.

A regiodivergent allylation of N-acylhydrazones with Morita-Baylis-Hillman (MBH) carbonates has been developed, providing α- or γ-allylated products in excellent yields by using different catalysts. The nature of the base catalyst plays a pivotal role in controlling the reaction pathway, allowing regiospecific access to diverse allylic substituted target compounds from identical substrates.

An NHC-catalyzed, stereoselective α-functionalization of α,ß-unsaturated carboxylic acids through in situ activation.

An N-heterocyclic carbene (NHC)-catalyzed α-functionalization of the in situ activated α,ß-unsaturated carboxylic acids bearing γ-H was realized through formal [4 + 2] annulations with o-quinone methides, which paved a new avenue for the assembly and modification of the dihydrocoumarin scaffold in good yields with excellent diastereo- and enantioselectivities.

Ligand-Free Copper(I)-Catalyzed Benzylic Acyloxylation of 2-Alkylpyridines under Aerobic Conditions.

A ligand-free copper(I)-catalyzed benzylic acyloxylation of 2-alkylpyridines with carboxylic acids was realized by using 1.0 atm of O2 as a green oxidant. The transformation provided a facile access to a wide range of N-heterocyclic esters through C-O bond formation, with broad substrate scope and good functional group tolerance. Preliminary mechanistic investigations showed that this protocol included a radical process.

NHC-Catalyzed Aldol-Like Reactions of Allenoates with Isatins: Regiospecific Syntheses of γ-Functionalized Allenoates.

An N-heterocyclic carbene (NHC) catalyzed γ-specific aldol-like reaction between allenoates and isatins has been achieved under mild conditions, giving trisubstituted allene derivatives bearing isatin moiety in moderate to good yields with high diastereoselectivity and excellent atom efficiency. The DFT computations indicated that the formation of the γ-adduct was more energetically favorable than that of the α-adduct. The result reported herein opens a new route for NHC-promoted allenoate-involved reaction.

An enantioselective assembly of naphthopyran via NHC-catalyzed [3 + 3] annulation of bromoenal with ß-tetralone.

An asymmetric assembly of naphthopyran was realized via the N-heterocyclic carbene (NHC)-catalyzed formal [3 + 3] annulation of bromoenal and ß-tetralone. The key advantages of this protocol include ready availability of starting materials, mild reaction conditions, good yields and excellent enantioselectivities.

NHC-Catalyzed Hetero-Diels-Alder Reaction of Allenoate with Chalcone: Synthesis of Polysubstituted Pyranyl Carboxylate.

An NHC-catalyzed hetero-Diels-Alder and isomerization process of chalcones with allenoates was discovered, which furnished highly functionalized multisubstituted pyranyl carboxylates successfully. This method features a convergent assembly, mild reaction conditions, moderate to good yields, and high atom economy.

NHC-catalyzed regiodivergent syntheses of difunctionalized 3-pyrazolidinones from α-bromoenal and monosubstituted hydrazine.

A formal [3 + 2] annulation of α-bromoenal with monosubstituted hydrazine could give 1,5 or 2,5-difunctionalized 3-pyrazolidinone regiodivergently by tuning the structure of the N-Heterocyclic Carbene (NHC) catalyst. Moderate to high yields, mild reaction conditions, good regioselectivity and potential biological significance of the final product have made this protocol attractive for the assembly of 3-pyrazolidinone.

N-Heterocyclic Carbene-Catalyzed [4 + 2] Cyclization of Saturated Carboxylic Acid with o-Quinone Methides through in Situ Activation: Enantioselective Synthesis of Dihydrocoumarins.

An N-heterocyclic carbene (NHC)-catalyzed formal [4 + 2] synthesis of dihydrocoumarins was realized from saturated carboxylic acids and o-quinone methides via an in situ activation strategy. This protocol results in excellent diastereoselectivity and enantioselectivity and good yields and uses readily available and inexpensive starting materials.

NHC-catalyzed [4 + 2] annulation of 2-bromo-2-enals with acylhydrazones: enantioselective synthesis of δ-lactams.

An asymmetric assembly of δ-lactams was realized via the NHC-catalyzed formal [4 + 2] annulation of acylhydrazones and 2-bromo-2-enals bearing γ-H. The advantages of this protocol include high enantioselectivity, good yields, mild reaction conditions and potential biological significance of the final products.