Catalytic Atroposelective Dynamic Kinetic Resolution of Biaryl Lactones with Activated Isocyanides

Abstract

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.

Catalytically atroposelective ring-opening of configurationally labile compounds to access axially chiral biaryls

“…Liao's group further implemented the Ag-catalyzed atroposelective DKR of Bringmann's lactone using a cinchona alkaloid-derived phosphine as the privileged chiral ligand. 13 They ingeniously designed activated isocyanides as the C-nucleophiles to trigger the tandem event, ring-open of lactones/rapid cyclization of isocyanide moiety, guarding against the stereochemical leakage problem resulted from lactol formation. A wide range of atropisomerically enriched oxazole-substituted biaryl phenols were assembled in high yields and high enantiopurities.…”

Enantioselective Synthesis of Axially Chiral Oxazole Biaryls by Copper‐Catalyzed Oxidation of Cyclic Diaryliodoniums

“…Oxazoles and their derivatives are one of the most important heterocycles in lots of natural and synthetic bioactive molecules displaying versatile biological activities [10] . However, axially chiral oxazole biaryls are rarely reported [11] . In this context, we report enantioselective intramolecular oxidation of cyclic diaryliodoniums for the efficient construction of axially chiral oxazoles under catalytic mild conditions and which can be further applied in asymmetric transformations as chiral catalysts (Scheme 1d).…”

“…[10] However, axially chiral oxazole biaryls are rarely reported. [11] In this context, we report enantioselective intramolecular oxidation of cyclic diaryliodoniums for the efficient construction of axially chiral oxazoles under catalytic mild conditions and which can be further applied in asymmetric transformations as chiral catalysts (Scheme 1d).…”

Stereo- and Regiospecific SN2′ Reaction of MBH Adducts with Isocyanoacetates: en Route to Transition-Metal-Free α-Allylation of Isocyanoacetates

“…Being a type of activated methylene compounds, isocyanoacetates have been widely employed as α-nucleophiles to attack electrophiles leading to a variety of nucleophilic addition and cycloaddition. Typical electrophilic acceptors include alkyl (pseudo)­halides, electron-deficient alkenes , and heterocycles, alkynes, cumulated double bonds, imines, carbonyls, , aziridines, nitrones, 1,3-dipoles, aryl diazonium salts and so forth. Morita–Baylis–Hillman (MBH) adducts, which have proven to be a type of versatile electrophiles, however, have never been reported to react with isocyanoacetates to the best of our knowledge.…”