The Development of the Intramolecular Asymmetric Heck Reaction

Abstract

This review summarises the development of the intramolecular Heck chemistry from its first report in 1977 to the present status of the reaction as a versatile methodology for the construction of carbocycles and heterocycles. Examples of the application of intramolecular Heck cyclisations as the key steps in the preparation of many complex natural product syntheses are given. The development of the intramolecular asymmetric Heck (IAH) reaction will also be detailed. The development of the IAH is summarised by focusing on the optimisation of palladium catalysts derived from a range of diphosphine and phoshinamine ligands for the preparation of a range of cyclic products, e.g. cis-decalins, hydrindans, indolizidines, diquinanes and the synthesis of quaternary carbon centres. The exploitation of this methodology to natural product synthesis will also be reviewed. Mechanistic insights (neutral versus cationic pathway) will be discussed. New ligands for the IAH will be described and will include recent results from our own work in the IAH. Keywords: asymmetric heck reaction, palladium catalysts, diphosphine, indolizidines, diquinanes, quaternary carbon centres