Gui-Ling Zhao

One‐Pot Organocatalytic Domino Michael/α‐Alkylation Reactions: Direct Catalytic Enantioselective Cyclopropanation and Cyclopentanation Reactions

The development of one-pot organocatalytic domino Michael/alpha-alkylation reactions between bromomalonates or bromoacetoacetate esters and alpha,beta-unsaturated aldehydes is presented. The chiral-amine-catalyzed reactions with bromomalonates as substrates give access to the corresponding 2-formylcyclopropane derivatives in high yields with excellent diastereoselectivity and up to 99 % ee. The catalytic domino Michael/alpha-alkylation reactions between 4-bromo-acetoacetate and enals provide a route for the synthesis of functionalized cyclopentanones in good to high yields with 93-99 % ee. The products from the organocatalytic reactions were also reduced with high diastereoselectivity to the corresponding cyclopropanols and cyclopentanols, respectively. Moreover, one-pot combinations of amine and heterocyclic carbene catalysis (AHCC) enabled the highly enantioselective synthesis of beta-malonate esters (91-97 % ee) from the reaction between bromomalonates and enals. The tandem catalysis included the catalytic domino reaction followed by catalytic in situ chemoselective ring-opening of the 2-formylcyclopropane intermediates.

Organocatalytic Asymmetric 5-Hydroxyisoxazolidine Synthesis: A Highly Enantioselective Route to β-Amino Acids

The highly chemo- and enantioselective organocatalytic tandem reaction between N-protected hydroxyl amines and alpha,beta-unsaturated aldehydes is presented; the reaction provides access to 5-hydroxyisoxazolidines and beta-amino acids in high yields and with 90-99% ee.

Dynamic Kinetic Asymmetric Transformation (DYKAT) by Combined Amine‐ and Transition‐Metal‐Catalyzed Enantioselective Cycloisomerization

The first examples of one-pot highly chemo- and enantioselective dynamic kinetic asymmetric transformations (DYKATs) involving alpha,beta-unsaturated aldehydes and propargylated carbon acids are presented. These DYKATs, which proceed by a combination of catalytic iminium activation, enamine activation, and Pd(0)-catalyzed enyne cycloisomerization, give access to functionalized cyclopentenes with up to 99 % ee and can be used for the generation of all-carbon quaternary stereocenters.

Dynamic Kinetic Asymmetric Domino Oxa‐Michael/Carbocyclization by Combination of Transition‐Metal and Amine Catalysis: Catalytic Enantioselective Synthesis of Dihydrofurans

A one-pot highly chemo- and enantioselective catalytic domino oxa-Michael/carbocyclization between α,β-unsaturated aldehydes and propargylic alcohols is presented. This dynamic kinetic transforma ...

Enantioselective Organocatalytic Conjugate Addition of Fluorocarbon Nucleophiles to α,β-Unsaturated Aldehydes

A highly chemo- and enantioselective organocatalytic addition of fluorocarbon nucleophiles, such as 1-fluoro-bis(phenylsulfonyl)methane, toα,β-unsaturated aldehydes is presented (see scheme). The reactions are catalyzed by simple chiral amines and give access to optically active fluorine derivatives in good yields and up to 95 % ee. Notably, the methodology can be applied to the formation of a chiral quaternary carbon center bearing a fluorine atom with high enantioselectivity.

Catalytic Asymmetric Aziridination of α,β-Unsaturated Aldehydes

The development, scope, and application of the highly enantioselective organocatalytic aziridination of α,β-unsaturated aldehydes is presented. The aminocatalytic azirdination of α,β-unsaturated aldehydes enables the asymmetric formation of β-formyl aziridines with up to >19:1 d.r. and 99% ee. The aminocatalytic aziridination of α-monosubstituted enals gives access to terminal α-substituted-α-formyl aziridines in high yields and up to 99% ee. In the case of the organocatalytic aziridination of disubstituted α,β-unsaturated aldehydes, the transformations were highly diastereo- and enantioselective and give nearly enantiomerically pure β-formyl-functionalized aziridine products (99% ee). A highly enantioselective one-pot cascade sequence based on the combination of asymmetric amine and N-heterocyclic carbene catalysis (AHCC) is also disclosed. This one-pot three-component co-catalytic transformation between α,β-unsaturated aldehydes, hydroxylamine derivatives, and alcohols gives the corresponding N-tert-butoxycarbonyl and N-carbobenzyloxy-protected β-amino acid esters with ee values ranging from 92-99%. The mechanisms and stereochemistry of all these catalytic transformations are also discussed.

Dynamic One‐Pot Three‐Component Catalytic Asymmetric Transformation by Combination of Hydrogen‐Bond‐Donating and Amine Catalysts

Dynamic one-pot three-component catalytic asymmetric transformation by combination of hydrogen-bond-donating and amine catalysts

One-pot catalytic asymmetric cascade synthesis of cycloheptane derivatives

A regiospecific, highly chemo-, diastereo-, and enantioselective one-pot catalytic cascade synthesis of cycloheptane derivatives is presented. In this chiral-amine-catalyzed asymmetric process, six new bonds and five new stereocenters were formed with excellent stereocontrol (>25:1 d.r. and 98- >99 ee).

One-Pot Catalytic Enantioselective Domino Nitro-Michael/Michael Synthesis of Cyclopentanes with Four Stereocenters

A highly enantioselective organocatalytic one-pot synthesis of nitro-, formyl-, and ester-functionalized cyclopentanes with four stereocenters is presented. The cyclopentanes were formed as a predominant diasteroisomer and isolated in high yields with 97-99 % ee.

Direct Catalytic Asymmetric Synthesis of Pyrazolidine Derivatives

A highly enantioselective, metal-free cascade reaction between di-1,2-N-protected hydrazine and α,β-unsaturated aldehydes is disclosed. The catalytic, asymmetric cascade transformation is a direct ...