Reductive amination of ketones with ammonium catalyzed by a newly identified Brevibacterium epidermidis strain for the synthesis of(S)-chiral amines

The asymmetric reductive amination of achiral ketones with ammonia is a particularly attractive reaction for the synthesis of chiral amines.Although several engineered amine dehydrogenases have been developed by protein engineering for the asymmetric reductive amination of ketones,they all display(R)‐stereoselectivity.To date,there is no report of an(S)‐stereoselective biocatalyst for this reaction.Herein,a microorganism named Brevibacterium epidermidis ECU1015 that catalyzes the(S)‐selective reductive amination of ketones with ammonium has been successfully isolated from soil.Using B.epidermidis ECU1015 as the catalyst,the asymmetric reductive amination of a set of phenylacetone derivatives was successfully carried out,yielding the corresponding(S)‐chiral amines with moderate conversion and>99%enantiomeric excess.

Divergent synthesis of chiral amines via Ni-catalyzed chemo-and enantioselective hydrogenation of alkynone imines

Ligand-mediated nickel-catalyzed asymmetric hydrogenation of alkynone imines has been achieved. By using Ni(OAc)_2·4H_2O/(S,S)-Ph-BPE complex as a catalyst, the chemo-and enantioselective hydrogenation of alkynone imines occurred efficiently to afford chiral propargyl amines with high yields and excellent enantioselectivities(up to 99% yield, >99% ee), leaving the readily reducible alkynyl group intact. Both the C=N and C≡C bonds of alkynone imines were hydrogenated efficiently in the presence of Ni(OAc)_2·4H_2O and Josiphos SL-J011-1, furnishing unfunctionalized chiral imines efficiently(up to 99% yield, >99% ee).The(Z)-allylamines and(E)-allylamines were also efficiently prepared from alkynone imines by the combination of the different catalytic systems. The preliminary mechanism study revealed that the reduction of alkynone imines was a stepwise process and the C=N bonds were preferably hydrogenated in the complete reduction of alkynone imines. The synthetic utility of this method was demonstrated by its application in the late-stage modification of the antiviral drug Zidovudine and the concise synthesis of chiral dibenzoazepine.

A Chiral Phosphorous Derivatizing Agent for the Determination of the Enantiomeric Excess of Chiral Alcohols, Amines by ^(31)P NMR

A chiral phosphorous derivatizing agent prepared from PCl3 and (S)-BINOL was described. It is used to determine the enantiomeric excess of chiral alcohols and amines by 31P NMR.

Copper-Catalyzed Asymmetric Three-Component Radical 1,2-Carboamination of Acrylamides with Arylamines: Access to Chiral α-Tertiary N-Arylamines

The asymmetric radical carboamination of 1,1-disubstituted alkenes from readily available alkyl halides and arylamines provides expedient access to valueadded chiralα-tertiary N-arylamines but has been less recognized.A challenge arises mainly from the difficult reaction initiation inherent in alkyl halides and the construction of fully substituted chiral C–N bonds from sterically congested tertiary alkyl radicals.Herein,we report a copper-catalyzed asymmetric three-component radical carboamination of acrylamides utilizing an anionic chiral N,N,N-ligand under mild conditions.This ligand was essential for the reaction initiation by enhancing the reducing capability of copper and enabling the enantiocontrol over tertiary alkyl radicals.The substrate scope was broad,covering an array of acrylamides,aryl-and heteroaryl-amines,as well as alkyl halides and sulfonyl chlorides,enabling good functional group tolerance.When combined with the follow-up transformation,this strategy provides a versatile platform for accessing structurally diverse chiralα-tertiary N-arylamine building blocks of interest in organic synthesis.

Divergent Protein Engineering of Transaminase for the Synthesis of Chiral Rivastigmine and Apremilast Precursors

Comprehensive Summary The implementation of divergent protein engineering on the natural transaminase Vf-ω-TA led to the development of two effective mutants(M2 and M8),enabling the enzymatic synthesis of chiral amine precursors of Rivastigmine and Apremilast,respectively.The evolution of the enzymes was guided by crystal structures and a focused mutagenesis strategy,allowing them to effectively address the challenging ketone substrates with significant steric hindrance.Under the optimized reaction parameters,transamination proceeded smoothly in good conversions and with perfect stereochemical control(>99%ee).These processes utilize inexpensiveα-methylbenzylamine as an amine donor and avoid the continuous acetone removal and costly LDH/GDH/NADH systems.

Asymmetric α-Pentadienylation of β-Ketocarbonyls and Aldehydes by Synergistic Pd/Chiral Primary Amine Catalysis

Direct alkylation with skipped enynes or cyclopropropylacetylenes represents an ideal process for the installation of pentadienyl group in terms of atom- and step-economy.The development of catalytic asymmetric versions has been frequently pursued and most of the successes have been achieved with enolizable aldehydes.We herein describe a synergistic chiral primary amine/Pd catalysis for asymmetric α-pentadienylation of β-ketocarbonyls and aldehydes with skipped enynes or cyclopropropylacetylenes.The reaction features the construction of acyclic all-carbon quaternary centers with high enantioselectivity,and good functional group tolerance and scalability.

Magnetic wrinkled organosilica-based metal-enzyme integrated catalysts for enhanced chemoenzymatic catalysis

Core-shell structured magnetic wrinkled organosilica-based metal-enzyme integrated catalysts were synthesized,and their catalytic performances were studied in the chemoenzymatic dynamic kinetic resolution of chiral amines in an organic solvent,as well as in the chemoenzymatic synthesis of chiral alcohols in water.Structureperformance studies revealed the important influence of their tunable structure and composition on the optimization of activity,stability,and recyclability in chemoenzymatic catalysis.

Iridium-Catalyzed Asymmetric Hydrogenation of Dialkyl Imines

Asymmetric hydrogenation of dialkyl imines to chiral amines is difficult because the two alkyls of imines are so similar in spatial and electronic structure that chiral catalysts are difficult to distinguish between them.In this study,we described an asymmetric hydrogenation of dialkyl imines by a chiral iridium catalyst containing spiro phosphine-amine-phosphine ligand.By precisely adjusting the chiral pocket of catalyst,a highly efficient catalyst was developed.Using this catalyst,a variety of dialkyl imines were hydrogenated to chiral amines with high yield and enantioselectivity.

Asymmetric hydroazidation ofα-substituted vinyl ketones catalyzed by chiral primary amine

We report herein the first example of asymmetric hydroazidation of α-substituted vinyl ketones by using chiral primary amines as the catalysts.A simple chiral primary-tertiary diamine catalyst derived from lphenylalanine was found to readily promote this aza-Michael addition reaction with enamine protonation as the key stereogenic step,thus enabling the effective synthesis of α-chiral β-azido ketones with good yields and moderate enantioselectivities.

Catalytic Asymmetric Addition and Telomerization of Butadiene with Enamine Intermediates

Herein,we report tunable asymmetric addition and telomerization of butadiene by synergistic chiral primary amine/achiral palladium catalysis.A selection of different achiral phosphine ligand in concert with the chiral primary amine-trifluoromethanesulfonic acid(TfOH)conjugates enables both chemo-and enantioselective control of the coupling with butadiene.Bidentate[(oxydi-2,1-phenylene)-bis-(diphenylphosphine)](DPEPhos)ligand led to 1,4-addition adduct whereas monodentate(p-Tol)3P ligand gave the telomerization product.A range ofα-branchedβ-ketoesters and aldehydes could be applied to afford allylation or telomerization products bearing allcarbon quaternary centers at high efficiency and good chemo-,regio-,and stereoselectivities.

Organocatalytic asymmetric [3+3] annulation of isatin N,N’-cyclic azomethine imines with enals:Efficient approach to functionalized spiro N-heterocyclic oxindoles

An unprecedented chiral secondary amine-catalyzed [3+3] annulation of isatin N,N’-cyclic azomethine imines with α,β-unsaturated aldehydes was developed.This strategy allowed the construction of structurally novel spiro N-heterocyclic oxindole derivatives in good yields(up to 91%) and good to excellent enantioselectivities(up to>99% ee),albeit with modest diastereoselectivities(up to 3.1:1 dr).

Multifunctional biocatalysis:An unusual imine reductase

A multifunctional biocatalyst EneIRED capable of catalyzing amine-activated conjugate alkene reduction and subsequent reductive amination was discovered.The enzyme realized the coupling ofα,β-unsaturated carbonyls with amines to efficiently synthesize a broad set of chiral amine diastereomers based on its unusual active site structure and catalytic mechanism.