Organic & Biomolecular Chemistry 2004-05-21

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

Janne E Tønder, Masood Hosseini, Alex B Ahrenst, David Tanner

Index: Org. Biomol. Chem. 2(10) , 1447-55, (2004)

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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% SN2' selectivity in the copper mediated addition of PhMgBr to geranyl chloride, as well as 99% and 95% SN2' 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 SN2 product. The allylic indole-containing substrates were also found to be unproductive in Pd- or Mo-catalysed SN2'-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.