Transition metal templates as guides for cyclizations

Abstract

The improvement of synthetic efficiency requires the development of more chemo-, regio-, diastereo- and enantioselective methods. Transition metal templates form the equivalent of an ‘active site’ to impose selectivity upon reacting organic systems. Such effects will be examined within the context of cyclization reactions. The first part examines cyclization reactions invoking intramolecular carbametallation. Catalytic reactions involving at least three different mechanisms and two different metals provide five- and six-membered rings from enynes and diynes. A second strategy invokes transition metal templates to facilitate macrocyclization. Formation of macrocarbocycles, macrolactones and macrocyclic ethers and amines illustrates the versatility of this approach. Most importantly, many of the macrocyclizations proceed at normal concentrations of 0.25-0.50 m . The third strategy invokes cycloadditions. A transition metal equivalent to the Diels-Alder reaction permits formation of odd membered rings by [2« + 3] cycloadditions for n = 1, 2 and 3. The applicability that such methods have in devising new synthetic strategies towards biologically important natural products will be illustrated.