Enantioselective Synthesis of Axially Chiral Tetrasubstituted Alkenes by Copper-Catalyzed C(sp)-H Functionalization of Arenes with Vinyl Cations.

Axially chiral tetrasubstituted alkenes are of increasing value and interest in chemistry-related areas. However, their catalytic asymmetric synthesis remains elusive, owing to the high steric repulsion and relatively low conformational stability. Herein, we disclose the straightforward construction of atropisomeric tetrasubstituted alkenes by effective enantiocontrol in a reaction with vinyl cation intermediates.

Asymmetric Büchner reaction and arene cyclopropanation via copper-catalyzed controllable cyclization of diynes.

The asymmetric Büchner reaction and related arene cyclopropanations represent one type of the powerful methods for enantioselective dearomatization. However, examples of asymmetric Büchner reactions via a non-diazo approach are quite scarce, and the related arene cyclopropanation based on alkynes has not been reported. Herein, we disclose an asymmetric Büchner reaction and the related arene cyclopropanation by copper-catalyzed controllable cyclization of N-propargyl ynamides via vinyl cation intermediates, leading to chiral tricycle-fused cycloheptatrienes and benzonorcaradienes in high yields and enantioselectivities.

Asymmetric formal C-C bond insertion into aldehydes via copper-catalyzed diyne cyclization.

The formal C-C bond insertion into aldehydes is an attractive methodology for the assembly of homologated carbonyl compounds. However, the homologation of aldehydes has been limited to diazo approach and the enantioselective reaction was rarely developed. Herein, we report an asymmetric formal C-C bond insertion into aldehydes through diyne cyclization strategy.

Organocatalytic intramolecular (4 + 2) annulation of enals with ynamides: atroposelective synthesis of axially chiral 7-aryl indolines.

Catalytic enantioselective transformation of alkynes has become a powerful tool for the synthesis of axially chiral molecules. Most of these atroposelective reactions of alkynes rely on transition-metal catalysis, and the organocatalytic approaches are largely limited to special alkynes which act as the precursors of Michael acceptors. Herein, we disclose an organocatalytic atroposelective intramolecular (4 + 2) annulation of enals with ynamides.

Copper-catalyzed enantioselective diyne cyclization C(sp)-O bond cleavage.

The functionalization of etheric C-O bonds C-O bond cleavage is an attractive strategy for the construction of C-C and C-X bonds in organic synthesis. However, these reactions mainly involve C(sp)-O bond cleavage, and a catalyst-controlled highly enantioselective version is extremely challenging. Here, we report a copper-catalyzed asymmetric cascade cyclization C(sp)-O bond cleavage, allowing the divergent and atom-economic synthesis of a range of chromeno[3,4-]pyrroles bearing a triaryl oxa-quaternary carbon stereocenter in high yields and enantioselectivities.

Construction of Axially Chiral Arylpyrroles via Atroposelective Diyne Cyclization.

Axially chiral biaryls widely exist in natural products and pharmaceuticals and are used as chiral ligands and catalysts in asymmetric synthesis. Compared to the well-established axially chiral 6-membered biaryl skeletons, examples of 5-membered biaryls have been quite scarce, and mono-substituted 3-arylpyrrole atropisomers have not been reported. Here, we disclose a copper-catalyzed atroposelective diyne cyclization for the construction of a range of axially chiral arylpyrrole biaryls in good to excellent yields with generally excellent enantioselectivities via oxidation and X-H insertion of vinyl cations.

Copper-Catalyzed Enantioselective Doyle-Kirmse Reaction of Azide-Ynamides via α-Imino Copper Carbenes.

[2,3]-Sigmatropic rearrangement reaction involving sulfonium ylide (Doyle-Kirmse reaction) generated from metal carbenes represents one of the powerful methods for the construction of C(sp )-S and C-C bonds. Although significant advances have been achieved, the asymmetric versions via the generation of sulfonium ylides from metal carbenes have been rarely reported to date, and they have so far been limited to diazo compounds as metal carbene precursors. Here, we describe a copper-catalyzed enantioselective Doyle-Kirmse reaction via azide-ynamide cyclization, leading to the practical and divergent assembly of an array of chiral [1,4]thiazino[3,2-b]indoles bearing a quaternary carbon stereocenter in generally moderate to excellent yields and excellent enantioselectivities.

Catalyst-Dependent Stereospecific [3,3]-Sigmatropic Rearrangement of Sulfoxide-Ynamides: Divergent Synthesis of Chiral Medium-Sized N,S-Heterocycles.

Medium-sized N,S-heterocycles have received tremendous interest due to their biological activities and potential medical applications. However, asymmetric synthesis of these compounds are extremely rare. Described herein is a catalyst-dependent [3,3]-sigmatropic rearrangement of sulfoxide-ynamides, enabling divergent and atom-economic synthesis of a series of valuable medium-sized N,S-heterocycles in moderate to good yields with broad substrate scope.