P(III)-Promoted Reductive Coupling of Aromatic and Aliphatic Nitro Compounds with Grignard Reagents.

A phosphine-promoted reductive coupling of nitro compounds with Grignard reagents is described. Polyfunctional and pharmaceutically relevant diarylamines were generated by this reaction in moderate to high yields. Aliphatic nitro compounds that are highly challenging substrates undergo a combination of α-arylation and reductive coupling to afford the α-arylated arylamines efficiently. A series of valuable biaryl compounds with polyfluorinated and heteroaryl rings are co-generated in 56-94% yields.

Organocatalytic enantioselective SN1-type dehydrative nucleophilic substitution: access to bis(indolyl)methanes bearing quaternary carbon stereocenters.

A highly general and straightforward approach to access chiral bis(indolyl)methanes (BIMs) bearing quaternary stereocenters has been realized via enantioconvergent dehydrative nucleophilic substitution. A broad range of 3,3'-, 3,2'- and 3,1'-BIMs were obtained under mild conditions with excellent efficiency and enantioselectivity (80 examples, up to 98% yield and >99 : 1 er). By utilizing racemic 3-indolyl tertiary alcohols as precursors of alkyl electrophiles and indoles as C-H nucleophiles, this organocatalytic strategy avoids pre-activation of substrates and produces water as the only by-product. Mechanistic studies suggest a formal SN1-type pathway enabled by chiral phosphoric acid catalysis. The practicability of the obtained enantioenriched BIMs was further demonstrated by versatile transformation and high antimicrobial activities (3al, MIC: 1 µg mL-1).

Computational Design of Enhanced Enantioselectivity in Chiral Phosphoric Acid-Catalyzed Oxidative Desymmetrization of 1,3-Diol Acetals.

A general method for the highly enantioselective desymmetrization of 2-alkyl-substituted 1,3-diols is presented. A combination of computational and experimental studies has been utilized to understand the origin of the stereocontrol of oxidative desymmetrization of 1,3-diol benzylideneacetals. DFT calculations demonstrate that the acetal protecting group is highly influential for high enantioselectivity, and a simple but effective new protecting group has been designed. The desymmetrization reactions proceed with high enantioselectivity for a variety of substrates. Moreover, the reaction conditions are also shown to be effective for desymmetrization of 2,2-dialkyl-substituted 1,3-diols, which provides chiral products bearing acyclic all-carbon quaternary stereocenters. The method has been applied to the formal synthesis of indoline alkaloids.

Catalytically Enantioselective Synthesis of Acyclic α-Tertiary Amines through Desymmetrization of 2-Substituted 2-Nitro-1,3-diols.

Highly enantioselective synthesis of acyclic α-tertiary amines through asymmetric desymmetrization is reported. This approach is based on chiral phosphoric acid mediated, enantioselective, oxidative desymmetrization of 2-substituted 2-nitro-1,3-diolbenzylidine acetals in the presence of DMDO as an oxidant. The method allows for the formation of a wide variety of chiral 2-nitro-1,3-diols in high enantioselectivity, which could be transformed into optically pure, unnatural α-alkyl series. The synthetic utility of this method has been further demonstrated by the expedient construction of the core structure of natural products manzacidins enantioselectively.

B(C6F5)3 catalyzed direct nucleophilic substitution of benzylic alcohols: an effective method of constructing C-O, C-S and C-C bonds from benzylic alcohols.

An efficient and general method of nucleophilic substitution of benzylic alcohols catalyzed by non-metallic Lewis acid B(C6F5)3 was developed. The reaction could be carried out under mild conditions and more than 35 examples of ethers, thioethers and triarylmethanes were constructed in high yields. Some bioactive organic molecules were synthesized directly using the methods.

Chiral phosphoric acid catalyzed highly enantioselective desymmetrization of 2-substituted and 2,2-disubstituted 1,3-diols via oxidative cleavage of benzylidene acetals.

A highly enantioselective catalytic protocol for the desymmetrization of a wide variety of 2-substituted and 2,2-disubstituted 1,3-diols is reported. This reaction proceeds through the formation of an "ortho ester" intermediate via oxidation of 1,3-diol benzylidene acetal by dimethyldioxirane (DMDO) and the subsequent proton transfer catalyzed by chiral phosphoric acid (CPA). The mechanism and origins of enantioselectivity of this reaction are identified using DFT calculations. The oxidation by DMDO is rate-determining, and the phosphoric acid significantly accelerates the proton transfer; the attractive interactions between the benzylidene part of the substrate and the 2,4,6-triisopropyl group of CPA are the key to high enantioselectivity.