Atroposelective Reactions

Abstract

Atropisomerism has opened new ways for DKR processes by exploiting the interconversion of atropisomeric unstable compounds as a beneficial property. The cleavage of a short bridge that causes configurational instability allows an elegant access to axially chiral biaryl products. Thus, Bringmann has demonstrated that biaryl lactones could be ring opened with chiral nucleophiles according to the principle of DKR. This cleavage can be achieved highly atropo-enantio- or -diastereoselectively by involving a range of chiral metallated nucleophiles including metallated amines, alcohols, C-nucleophiles or hydride transfer reagents; by using uncharged chiral or achiral nucleophiles after Lewis acid activation of the lactone; or by involving a η6-coordination of a transition metal fragment to one of the aromatic rings of the biaryl lactone. Moreover, the last fifteen years have seen novel families of atropisomers based on structures other than biaryls come forward as potential new starting materials for DKRs. Among them, atropisomeric anilides, benzamides and naphthamides have been resolved through DKR. Despite the prevalence and importance of atropisomerism in organic structures, the field of asymmetric catalysis has not yet recorded extensive success in the development of catalysis. Among the best recent results of atropo-enantioselective reactions are aldol reactions of atropisomeric benzamides and naphthamides using L-proline as organocatalyst developed by Walsh; nickel-catalysed cross coupling of dibenzothiophenes with Grignard reagents performed in the presence of chiral phosphines developed by Hayashi; ring-opening of biaryl lactones with methanol catalysed by AgBF4 combined with (R)-BINAP developed by Yamada; and DKR of biaryl atropisomers via peptide-catalysed bromination developed by Miller.