Directed Lithiation/Transmetalation Approach to Palladium-Catalyzed Cross-Coupling Acylation Reactions

摘要

The directed ortho-lithiation method of electrophilically functionalizing a variety of substrates has become a very powerful synthetic tool for target-directed synthesis. Indeed, since its conception by Gilman and Wittig over 50 years ago there has been widespread development in this area. The early work of Gilman and Hauser provided the impetus for the subsequent contributions from a number of groups which have expanded the scope of the reaction to a variety of substituted aromatic and olefinic substrates, in addition to providing important mechanistic information. This area of investigation has been reviewed on several occasions and has become a sophisticated method in organic synthesis. An array of directing groups have emerged which are capableof enhancing ortho-deprotonations and have a hierachial order of directing ability. This allows rational prediction of the reactivity of a particular substrate, which may be explained in terms of a complimentary interplay between inductive and complexation effects. Indeed, the ability of a species to effect the nature of a substituent in close proximity has been rationalized in terms of the complex-induced proximity effect (CIPE) proposed by Beak and Meyers.