Total synthesis of (-)-cylindrocyclophane A facilitated by C-H functionalization.

(-)-Cylindrocyclophane A is a 22-membered C-symmetric [7.7]paracyclophane that bears bis-resorcinol functionality and six stereocenters. We report a synthetic strategy for (-)-cylindrocyclophane A that uses 10 C-H functionalization reactions, resulting in a streamlined route with high enantioselectivity and efficiency (17 steps).

Diaryldiazoketones as Effective Carbene Sources for Highly Selective Rh(II)-Catalyzed Intermolecular C-H Functionalization.

A novel donor/acceptor carbene intermediate has been developed using diaryldiazoketones as carbene precursors. In the presence of the chiral dirhodium catalyst, Rh(-TPPTTL), 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.

A C-H Functionalization Strategy Enables an Enantioselective Formal Synthesis of (-)-Aflatoxin B.

An enantioselective formal synthesis of (-)-aflatoxin B 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.

Catalyst-Controlled Selective Functionalization of Unactivated C-H Bonds in the Presence of Electronically Activated C-H Bonds.

A new chiral dirhodium tetracarboxylate catalyst, Rh( S-2-Cl-5-BrTPCP), 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 C 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.