2-Azadienes as Enamine Umpolung Synthons for the Preparation of Chiral Amines.

The development of new strategies for the preparation of chiral amines is an important objective in organic synthesis. In this , we summarize our approach for catalytically accessing nucleophilic aminoalkyl metal species from 2-azadienes, and its application in generating a number of important but elusive chiral amine scaffolds. Reductive couplings with ketones and imines afford 1,2-amino tertiary alcohols and 1,2-diamines, respectively, whereas fluoroarylations of -difluoro-2-azadienes deliver α-trifluoromethylated benzylic amines.

Palladium-Catalyzed Synthesis of -Trifluoromethyl Benzylic Amines via Fluoroarylation of -Difluoro-2-azadienes Enabled by Phosphine-Catalyzed Formation of an Azaallyl-Silver Intermediate.

We report the synthesis of -trifluoromethyl benzylic amines through the vicinal fluoroarylation of difluoro-2-azadienes. Our studies indicate that XPhos plays an important role as a phase transfer catalyst that promotes the addition of AgF to the difluoroazadiene, generating an trifluoromethyl azaallyl-silver intermediate that we have characterized by NMR spectroscopy. This intermediate likely transmetallates to Pd, coupling several aryl iodides to deliver products in up to 90% yield.

Enantioselective Synthesis of anti-1,2-Diamines by Cu-Catalyzed Reductive Couplings of Azadienes with Aldimines and Ketimines.

Here we report highly efficient and chemoselective azadiene-imine reductive couplings catalyzed by (Ph-BPE)Cu-H that afford anti-1,2-diamines. In all cases, reactions take place with either aldimine or ketimine electrophiles to deliver a single diastereomer of product in >95:5 er. The products' diamines are easily differentiable, facilitating downstream synthesis.

2-Azadienes as Reagents for Preparing Chiral Amines: Synthesis of 1,2-Amino Tertiary Alcohols by Cu-Catalyzed Enantioselective Reductive Couplings with Ketones.

We introduce a new strategy for synthesis of chiral amines: couplings of α-aminoalkyl nucleophiles generated by enantioselective migratory insertion of 2-azadienes to a Cu-H. In this report, we demonstrate its application in catalytic reductive coupling of 2-azadienes and ketones to furnish 1,2-amino tertiary alcohols with vicinal stereogenic centers.

Diastereoselective and Enantiospecific Synthesis of 1,3-Diamines via 2-Azaallyl Anion Benzylic Ring-Opening of Aziridines.

The 1,3-diamine motif appears in numerous complex molecules, yet there are few methods for the stereoselective construction of this moiety. Herein, we demonstrate a stereocontrolled synthesis of 1,3-diamines, which bear up to three contiguous stereogenic centers, through benzylic ring-opening of aziridines with 2-azaallyl anion nucleophiles. Reactions proceed efficiently (yield up to 95%), diastereoselectively (dr up to >20:1), site selectively, and enantiospecifically to deliver products with differentiated amino groups.

A New Descriptor of Amino Acids-SVGER and its Applications in Peptide QSAR.

In the study of peptide quantitative structure activity relationship (QSAR), a new descriptor of amino acids (SVGER) was calculated. It was applied in two peptides which are angiotensin converting enzyme inhibitors and bitter tasting threshold of di-peptide. QSAR models were built by stepwise multiple regression-multiple linear regression (SMR-MLR) and stepwise multiple regression-partial least square regression (SMR-PLS).

Asymmetric synthesis of heteroaryl atropisomers via a gold-catalyzed cycloisomerization-amination cascade reaction.

The chiral gold(i) complex enables enantioselective cycloisomerization-amination of 2-(alkynyl)phenyl boronic acids and diazenes in high yields. A wide scope of substrates bearing various functional groups was tolerated to generate structurally different hydrazide derivatives as a new type of atropisomer.

Catalytic cascade hydroalkoxylation/isomerization/ [4 + 2] cycloaddition using enyne alcohols as latent dienes or dienophiles.

Enyne alcohols can react as precursors of either dienes or dienophiles with different substrates after hydroxylation and isomerization by gold catalysis. As such, oxa-bridged tricyclo[5.2.

Enantioselective relay catalytic cascade intramolecular hydrosiloxylation and Mukaiyama aldol reaction.

Cascading chemistry! The first practical relay catalytic cascade intramolecular hydrosiloxylation of arylacetylene and asymmetric Mukaiyama aldol reaction has been established to give synthetically useful products in high yields and with excellent ee (see scheme).

Chiral gold complex-catalyzed hetero-Diels-Alder reaction of diazenes: highly enantioselective and general for dienes.

A chiral gold(I) complex-catalyzed highly regio- and enantioselective azo hetero-Diels-Alder reaction has been developed. The chiral gold(I) complex acting as a Lewis acid exhibits high efficiency in the activation of urea-based diazene dienophiles. Moreover, this chiral gold catalyst also rendered a cascade intramolecular enyne cycloisomerization/asymmetric azo-HDA reaction.