Cyclic anhydrides as electrophilic partners in transition metal-catalyzed cross-coupling reactions: reaction development and synthetic applications

Abstract

A nickel mediated decarbonylative cross coupling of cyclic anhydrides and diorganozinc reagents has been developed. The process involves the oxidative addition of a low-valent nickel catalyst to a cyclic anhydride coupling partner which, upon decarbonylation, furnishes nickelalactone intermediates that are intercepted by organozinc coupling partners supplying cross coupled carboxylic acid products. Cyclic anhydrides bearing substituted backbones participate in the reaction constituting one of the first examples of the introduction of stereochemical information via an electrophilic coupling partner in a transition metal mediated C-C bond forming reaction. A nickel-catalyzed alkylation of succinic and glutaric anhydrides with diorganozinc reagents has been realized. The reaction scope is remarkably broad with respect to both electrophilic and nucleophilic coupling partners providing ready access to highly functionalized 1,4- and 1,5-keto acid derivatives. The addition of styrene promoters has been shown to effect dramatic rate enhancements. The enantioselective variant of the reaction has also been investigated with limited success. The asymmetric alkylative desymmetrization of meso succinic anhydrides with dialkyl- and diarylzinc reagents in the presence of catalytic amounts of a chiral palladium complex has been developed. The reaction proceeds at room temperature in many cases supplying the product keto acids containing up to four stereocenters in high yield and enantiomeric excess. The synthetic utility of the keto acid products derived from the transition metal catalyzed cross-coupling reactions has been briefly investigated. An efficient complementary diastereoselective reduction of 1,4-keto acids bearing cyclic backbones has been discovered. Reduction of keto acids in the presence of two different reducing agents provides ready access to each diastereomer of the product trisubstituted γ-lactone derivatives. In addition, the nickel catalyzed alkylation of succinic anhydrides has been applied to the synthesis natural products, culminating in the efficient preparation of five members of the lignan family of natural products.