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.

Catalytic asymmetric dynamic kinetic resolution of configurationally labile bridged biaryls is emerging as a powerful strategy for atropisomer synthesis. However, the reported examples suffer from an inherent challenge as the reactivity is highly dependent on the torsional strain of the biaryl substrates, which significantly narrows down the scope and hampers the application. Herein, we report our discovery and development of a torsional strain-independent reaction between biaryl thionolactones and activated isocyanides. By employing auto-tandem silver catalysis, a universal synthesis of both tri-and tetra-ortho-substituted thiazole-containing biaryls was realized in high yields with high enantioselectivities. In addition, these products could be facilely converted to a novel type of bridged biaryls bearing an eight-membered lactone. Mechanistic studies were carried out to elucidate the cause of this unusual torsional strain-independent reactivity.

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). In addition, the same catalytic system could be applied to both the late‐stage functionalization of complex bioactive molecules and the kinetic resolution of racemic azomethine imines, further highlighting its versatility and synthetic utility.

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...

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...