Studies of the formation of all-carbon quaternary centres, en route to lyngbyatoxin A. A comparison of phenyl and 7-substituted indole systems

Abstract

Copper mediated allylic substitutions and conjugate additions to geranyl, cinnamyl and allylic indole compounds have been investigated with the aim of finding a method for the creation of the all-carbon quaternary centre present in the natural product lyngbyatoxin A. Reaction conditions have been found giving a 68% S_N2′ selectivity in the copper mediated addition of PhMgBr to geranyl chloride, as well as 99% and 95% S_N2′ selectivity in the copper catalysed addition of EtMgBr to cinnamyl chloride and acetate, respectively. When the optimised reaction conditions were applied to the corresponding allylic compounds containing a 7-substituted indole moiety, the regioselectivity was reversed giving only the S_N2 product. The allylic indole-containing substrates were also found to be unproductive in Pd- or Mo-catalysed S_N2′-type substitution reactions. In related studies, copper catalysed conjugate addition of EtMgBr to the tricyclic lactam 6-methyl-pyrrolo[3,2,1-ij]quinolin-4-one gave a maximum of 20% of the 1,4-addition product.