Trimethylsilyl (TMS)-protected alkynes served as selective alkyne cross-coupling partners in titanium-catalyzed [2+2+1] pyrrole synthesis. Reactions of TMS-protected alkynes with internal alkynes and azobenzene under the catalysis of titanium imido complexes yielded pentasubstituted 2-TMS-pyrroles with greater than 90 % selectivity over the other nine possible pyrrole products. The steric and electronic effects of the TMS group were both identified to play key roles in this highly selective pyrrole synthesis. This strategy provides a convenient method to synthesize multisubstituted pyrroles as well as an entry point for further pyrrole diversification through facile modification of the resulting 2-silyl pyrrole products, as demonstrated through a short formal synthesis of the marine natural product lamellarin R.
Bibliographical noteFunding Information:
Financial support was provided by the National Institutes of Health (1R35GM119457). The Chemistry Department NMR facility is supported through a grant from the National Institutes of Health (S10OD011952) with matching funds from the University of Minnesota. IAT is a 2017 Alfred P. Sloan Fellow.
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- multicomponent reactions