Chiral Brønsted Acid from Chiral Phosphoric Acid Boron Complex and Water: Asymmetric Reduction of Indoles.

A new chiral Brønsted acid, generated in situ from a chiral phosphoric acid boron (CPAB) complex and water, was successfully applied to asymmetric indole reduction. This "designer acid catalyst", which is more acidic than TsOH as suggested by DFT calculations, allows the unprecedented direct asymmetric reduction of C2-aryl-substituted N-unprotected indoles and features good to excellent enantioselectivities with broad functional group tolerance. DFT calculations and mechanistic experiments indicates that this reaction undergoes C3-protonation and hydride-transfer processes. Besides, bulky C2-alkyl-substituted N-unprotected indoles are also suitable for this system.

Organocatalytic asymmetric arylation of indoles enabled by azo groups.

Arylation is a fundamental reaction that can be mostly fulfilled by electrophilic aromatic substitution and transition-metal-catalysed aryl functionalization. Although the azo group has been used as a directing group for many transformations via transition-metal-catalysed aryl carbon-hydrogen (C-H) bond activation, there remain significant unmet challenges in organocatalytic arylation. Here, we show that the azo group can effectively act as both a directing and activating group for organocatalytic asymmetric arylation of indoles via formal nucleophilic aromatic substitution of azobenzene derivatives. Thus, a wide range of axially chiral arylindoles have been achieved in good yields with excellent enantioselectivities by utilizing chiral phosphoric acid as catalyst. Furthermore, highly enantioenriched pyrroloindoles bearing two contiguous quaternary chiral centres have also been obtained via a cascade enantioselective formal nucleophilic aromatic substitution-cyclization process. This strategy should be useful in other related research fields and will open new avenues for organocatalytic asymmetric aryl functionalization.

Organocatalytic Atroposelective Arylation of 2-Naphthylamines as a Practical Approach to Axially Chiral Biaryl Amino Alcohols.

The first phosphoric acid catalyzed direct arylation of 2-naphthylamines with iminoquinones for the atroposelective synthesis of axially chiral biaryl amino alcohols has been developed. This reaction constitutes a highly functional-group-tolerant route for the rapid construction of enantioenriched axially chiral biaryl amino alcohols, and is a rare example of 2-naphthylamines acting as nucleophiles in an organocatalytic enantioselective transformation. Furthermore, the products, which feature various halogen atoms, provide access to structurally diverse axially chiral amino alcohols through further transformations.

A cinchona alkaloid catalyzed enantioselective sulfa-Michael/aldol cascade reaction of isoindigos: construction of chiral bispirooxindole tetrahydrothiophenes with vicinal quaternary spirocenters.

A cinchona alkaloid catalyzed diastereoselective and enantioselective sulfa-Michael/aldol cascade reaction between 1,4-dithiane-2,5-diol and isoindigos has been successfully developed to afford the highly congested bispirooxindole tetrahydrothiophenes with vicinal quaternary spirocenters in high yields (up to 91%), excellent diastereoselectivities (up to >20 : 1 dr), and good enantioselectivities (up to 98% ee). Some synthetic transformations of the reaction products were also studied.

Asymmetric synthesis of 3,3'-spirooxindoles fused with cyclobutanes through organocatalytic formal [2 + 2] cycloadditions under H-bond-directing dienamine activation.

The first organocatalytic asymmetric synthesis of a spirooxindole skeleton incorporated with a cyclobutane moiety has been successfully developed on the basis of H-bond-directing dienamine activation. Structurally complex spirocyclobutyl oxindoles, which possess four contiguous stereocenters, including one spiro quaternary center, were obtained in good yields (up to 83%) with excellent ß,γ-regioselectivity (>19:1) and stereocontrol (up to >19:1 dr and 97% ee).

Organocatalytic stereocontrolled synthesis of 3,3'-pyrrolidinyl spirooxindoles by [3+2] annulation of isocyanoesters with methyleneindolinones.

A stereoselective [3+2] cycloaddition of isocyanoesters to methyleneindolinones catalyzed by a quinine-based thiourea-tertiary amine has been successfully developed. Just by tuning the protecting groups on substrates, a variety of optically enriched 3,3'-pyrrolidinyl spirooxindole diastereomers could be obtained in excellent enantioselectivities (up to 99% ee).