RESUMO
A novel donor/acceptor carbene intermediate has been developed using diaryldiazoketones as carbene precursors. In the presence of the chiral dirhodium catalyst, Rh2(S-TPPTTL)4, diaryldiazoketones undergo highly regio-, stereo-, and diastereoselective C-H functionalization of activated and unactivated secondary and tertiary C-H bonds. Computational studies revealed that the arylketo group behaves differently than the carboxylate acceptor group because the orientation of the arylketo group predetermines which face of the carbene will be attacked.
RESUMO
An enantioselective formal synthesis of (-)-aflatoxin B2 from 4-methoxyphenylacetic acid has been achieved by an approach that produces a key carbon-carbon bond, a benzylic stereocenter, and two arene carbon-oxygen bonds in the course of three site-selective C-H functionalizations. The carbonyl-directed acetoxylation of two arene C-H bonds described herein is unprecedented in natural product synthesis and occurs under mild conditions that preserve the configuration of a sensitive benzylic stereocenter.
Assuntos
Aflatoxina B1RESUMO
A new chiral dirhodium tetracarboxylate catalyst, Rh2( S-2-Cl-5-BrTPCP)4, has been developed for C-H functionalization reactions by means of donor/acceptor carbene intermediates. The dirhodium catalyst contains four ( S)-1-(2-chloro-5-bromophenyl)-2,2-diphenylcyclopropane-1-carboxylate ligands, in which all four 2-chloro-5-bromophenyl groups are on the same face of the catalyst, leading to a structure, which is close to C4 symmetric. The catalyst induces highly site selective functionalization of remote, unactivated methylene C-H bonds even in the presence of electronically activated benzylic C-H bonds, which are typically favored using earlier established dirhodium catalysts, and the reactions proceed with high levels of diastereo- and enantioselectivity. This C-H functionalization method is applicable to a variety of aryl and heteroaryl derivatives. Furthermore, the potential of this methodology was illustrated by sequential C-H functionalization reactions to access the macrocyclic core of the cylindrocyclophane class of natural products.