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.

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.

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.

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.

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).