Transition metal templates for selectivity in organic synthesis
Palladium templates offer new avenues of selectivity as exemplified by four disparate problems in allylic alkylation. In the first, control of absolute and relative stereochemistry on conformationally non-rigid systems is considered in the context of the side chains of Vitamins E and K. The second problem deals with reorientation of the [3.3] sigmatropic rearrangement of alkylidenevinyltetrahydrofurans, readily available via three different routes, which produces cycloheptenones to a [l.3 rearrangement which produces vinylcyclopentanones, including prostanoid analogs. A cycloaddition approach to cyclopentane synthesis constitutes the subject of the third problem. Palladium(O) complexes of trimethylenemethanes, which form from 2-trimethylsilylmethylallyl acetates, cycloadd to electron deficient olefins to give methylenecyclopentanes in both interand intramolecular versions. The fourth section deals with macrocyclization. Palladium initiated cyclizations exhibit a remarkable degree of control of ring size not available in non-transition metal reactions. Applications to the cytochalasin and erythrynolide familes of compounds are discussed. A key aspect of synthetic design is efficiency the ability to transform readily available starting materials to particular target compounds via the shortest route. Synonymous with efficiency is selectivity which may be grouped into three major classes 1) chemoselectivity or functional group differentiation, 2) regioselectivity or orientational control in the reaction of an unsymmetrical functional group and/or an unsymmetrical reagent and 3) stereocontrol or control of relative stereochemistry (diastereoselectivity) and/or control of absolute stereochemistry (enantioselectivity). The unique position of the carbonyl group in synthetic design stems from the selective formation of bonds at the carbonyl carbon atom or the alpha carbon atom according to equation 1. OH o a NUC..H 1L-ELEC, (1)