N-H Insertion reactions of rhodium carbenoids. Part 3. The development of a modified Bischler indole synthesis and a new protecting-group strategy for indoles

A modified version of the Bischler indole synthesis has been developed in which the key step is the N-H insertion reaction of rhodium carbene intermediates derived from alpha-diazo-beta-ketoesters with anilines. Thus N-methylanilines 1 react with diazoketoesters 2 in the presence of dirhodium(II) acetate to give (N-arylamino) ketones 3, cyclisation of which using boron trifluoride-ethyl acetate or acidic ion exchange resin gives the indoles 4. In order to extend this method to the synthesis of N-unsubstituted indoles, a new protecting group strategy for indoles was developed. In this, anilines are reacted with alpha,beta-unsaturated-esters or -sulfones to give the conjugate addition products 6 and 9, cyclisation of which gives indoles 8 and 11. The N-(2-ethoxycarbonylethyl)- and -(2-sulfonylethyl)-protecting groups are readily removed from indoles 8 and 11 by treatment with base.