Diastereo- and enantioselective synthesis of biaryl aldehydes bearing both axial and central chirality.

We describe herein an intriguing method for the synthesis of biaryl aldehydes bearing both axial and central chirality through a desymmetric [3 + 2] cycloaddition reaction of activated isocyanides with prochiral biaryl dialdehydes under silver catalysis. This protocol features excellent enantioselectivity, 100% atom economy, good functional group compatibility, and operational simplicity.

Cooperative catalysis-enabled C-N bond cleavage of biaryl lactams with activated isocyanides.

The catalytic reaction of biaryl lactams with activated isocyanides is reported for the first time. By employing a cooperative catalytic system, oxazole-containing axially chiral biaryl anilines were obtained in high yields with excellent enantioselectivities. The key to the success lies in the atroposelective amide C-N bond cleavage with activated isocyanides.

Diastereo- and Enantioselective Silver-Catalyzed [3+3] Cycloaddition and Kinetic Resolution of Azomethine Imines with Activated Isocyanides.

In contrast to the well-established [3+2] cycloaddition reactions, the catalytic enantioselective [3+n] (n≥3) cycloaddition reaction of activated isocyanides for the preparation of six-membered or larger ring systems has remained underdeveloped. Herein, we report the first example of highly diastereo- and enantioselective [3+3] cycloaddition of activated isocyanides with azomethine imines. By employing silver catalysis, a wide range of biologically important bicyclic 1,2,4-triazines were obtained in high yields (up to 99 %) with good to excellent stereoselectivities (up to >20 : 1 dr, 99 % ee).

Catalytic Atroposelective Dynamic Kinetic Resolution of Biaryl Lactones with Activated Isocyanides.

We report herein an unprecedented atroposelective dynamic kinetic resolution of Bringmann's lactones with C-nucleophiles. By the use of activated isocyanides as the reagent, a wide range of novel axially chiral oxazole-substituted biaryl phenols were accessed in high yields with high enantioselectivities. Key to the success of this process lies in the tandem atroposelective addition of isocyanides to the lactone substrate followed by a rapid cyclization, overcoming the challenge of stereochemical leakage induced by lactol formation.