The 2,6-dibromoindole 5 underwent regioselective Sonogashira coupling at the 2 position with simple acetylenic partners. While, the imidazole-acetylene 16 failed to couple to 5, the cyclic carbonate 19 succeeded to give 20, which was further elaborated into the indole-imidazole 23.
KeywordsChartelline C; securines; securamines; biogenetic; Sonogashira couplingThe chartelline marine alkaloids were isolated from the bryozoan Chartella papyracea and characterized in the 1980's. 1-3 A related bryozoan Securiflustra securifrons also produces the securines and securamines, 4,5 and they are plausible biogenetic precursors to the chartellines. It was reported that solutions of securine B 1 in DMSO-d 6 converted into securamine B 2, presumably via 1a , Scheme 1. 4 Redissolving 2 in CDCl 3 converted 2 back into 1. One could imagine that if this isomerization were carried out in the presence of an electropositive source of chlorine, 1 could be converted into chartelline C 3 through the intermediacy of 1b and 1c. The transformation of 1c into 3 can be written as a [1,5]-shift and is a key step in the recently reported biogenetically inspired strategy for the synthesis of 3 by Baran and Shenvi. 6,7 Several other groups have reported on synthetic approaches to chartelline C 6,8-11 as well as related alkaloids. 12,13 Our plan was also based on the supposition that the spiro-β-lactam in 3 could arise from a late stage oxidative cyclization of a suitable macrolactam. 14 The macrolactam precursor to 1c, namely 1, was envisioned as arising from macrolactamization, and to eventually achieve this a regioselective Sonogashira coupling at the 2-position of a 2-halo-6-bromoindole was required as a starting point. The only selective coupling of an acetylene at the 2-position of an indole that has a 6-bromo substituent was a 2-iodo-6-bromoindole, 7 and since this compound required a six step synthesis from 6-bromoindole, we were interested to see if a 2,6-dibromoindole exhibited any selectivity in a Sonogashira coupling reaction.Indole-3-acetonitrile 4 15,16 was regioselectively brominated using a known protocol 17 to give 5 (after t-butyl carbamate protection), Scheme 2. Exposure of 5 to standard Sonogashira © 2007 Elsevier Ltd. All rights reserved.Tel +1 512 471 3966: Fax +1 512 471 7839: p.magnus@mail.utexas.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. coupling reaction conditions proceeded with complete regioselectivity to give the 2-coupled indoles 6, 7 and 8 respectively. It was found that the choice of protecting group on the indole nitrogen atom was essential to achieving r...