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

摘要

A modified version of the Bischler indole synthesis has been developed in which the key step is the N–H insertionnreaction of rhodium carbene intermediates derived from α-diazo-β-ketoesters with anilines. Thus N-methylanilinesn1 react with diazoketoesters 2 in the presence of dirhodium() acetate to give (N-arylamino)ketones 3, cyclisation ofnwhich using boron trifluoride–ethyl acetate or acidic ion exchange resin gives the indoles 4. In order to extend thisnmethod to the synthesis of N-unsubstituted indoles, a new protecting group strategy for indoles was developed. Innthis, anilines are reacted with α,β-unsaturated-esters or -sulfones to give the conjugate addition products 6 and 9,ncyclisation of which gives indoles 8 and 11. The N-(2-ethoxycarbonylethyl)- and -(2-sulfonylethyl)- protectingngroups are readily removed from indoles 8 and 11 by treatment with base.