Cinchona Alkaloid Catalyzed Dynamic Kinetic Resolution of Biaryl Aldehydes via Asymmetric Decarboxylative Transamination

Abstract

The unprecedented Cinchona alkaloid catalyzed atropoenantioselective transamination of biaryl aldehydes with 2,2-diphenylglycine via a cascade decarboxylation and dynamic kinetic resolution strategy is described. This protocol features broad substrate scope and good functional group tolerance and allows the rapid assembly of axially chiral biaryls in high yields with acceptable to good enantioselectivities. In addition, such structural motifs may have potential applications in enantioselective catalysis as chiral ligands or catalysts.

Organocatalytic Atroposelective Dynamic Kinetic Resolution Involving Ring Manipulations

“…The OH group is also important in atroposelec- In the same year, the Wang group made use of quinine-catalyzed enantioselective decarboxylative transamination of biaryl aldehydes 18' or 24 with 2,2diphenyl glycine to realize dynamic kinetic resolution, allowing rapid assembly of axially chiral biaryl amino alcohol and diamine products 30 in 80-92% yields with acceptable to good ee values (30-66%) under mild reaction conditions (Scheme 12). [40] The catalytic cycle begins with the condensation of biaryl aldehydes with 2, Axially chiral styrenes, pioneered by Adams and co-workers in the 1940s, [41] have gained increasing attention owing to their great potential as chiral ligands in asymmetric synthesis. Compared with aryl-cycloalkene atropisomers in which the alkene is trapped in a ring to increase the rigidity of products, the construction of axially chiral styrenes bearing non-cyclic olefin moiety remains challenging because of the perceived lower rotational barrier around the C(vinyl)À C(aryl) single bond and hence lower stereochemical stability.…”

“…In the same year, the Wang group made use of quinine‐catalyzed enantioselective decarboxylative transamination of biaryl aldehydes 18’ or 24 with 2,2‐diphenyl glycine to realize dynamic kinetic resolution, allowing rapid assembly of axially chiral biaryl amino alcohol and diamine products 30 in 80–92% yields with acceptable to good ee values (30–66%) under mild reaction conditions (Scheme 12). [40] The catalytic cycle begins with the condensation of biaryl aldehydes with 2,2‐diphenyl glycine to form imines 31 / 31’ . Interconversion of 31’ ⇄ Int‐8 ⇄ 31 continuously provides enantiomer 31 , which undergoes a faster transformation than 31’ in the presence of Cat.…”

Development of Configurationally Labile Biaryl Reagents for Atropisomer Synthesis

“…The in situ formed hemiaminals may be crucial to the dynamic kinetic resolution of the racemic amino aldehyde substrates, but the possibility of dynamic kinetic resolution via lactam intermediates in the reaction cannot be ruled out. The same group also reported a cinchona alkaloid‐catalyzed dynamic kinetic transformation of biaryl aldehydes via asymmetric decarboxylative transamination (Scheme 22b) [78] . Chi, Zhang, Jin, and co‐workers developed a N ‐heterocyclic carbene‐catalyzed atroposelective nitrile formation method, providing axially chiral tetra‐ ortho ‐substituted biaryl benzonitriles (Scheme 22c) [79] .…”

“…The same group also reported a cinchona alkaloidcatalyzed dynamic kinetic transformation of biaryl aldehydes via asymmetric decarboxylative transamination (Scheme 22b). [78] Chi, Zhang, Jin, and co-workers developed a N-heterocyclic carbene-catalyzed atroposelective nitrile formation method, providing axially chiral tetra-ortho-substituted biaryl benzonitriles (Scheme 22c). [79] The dynamic kinetic resolution process was realized via lactol and N,O-acetal intermediates.…”