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Dative Directing Group Effects in Ti-Catalyzed [2+2+1] Pyrrole Synthesis: Chemo- and Regioselective Alkyne
Hsin-Chun Chiu1, Xin Yi See1, Ian A Tonks1
1Department of Chemistry, University of Minnesota-Twin Cities, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, United States.
Abstract:
Transient dative substrate-Ti interactions have been found to play a key role in controlling the regioselectivity of alkyne insertion and [2+2] cycloaddition in Ti-catalyzed [2+2+1] pyrrole synthesis and Ti-catalyzed alkyne hydroamination. TMS-protected alkynes with pendent Lewis basic groups can invert the regioselectivity of TMS-protected alkyne insertion, leading to the selective formation of highly substituted 3-TMS pyrroles. The competency of various potential directing groups was investigated, and it was found that the directing-group effect can be tuned by modifying the catalyst Lewis acidity, the directing-group basicity, or the directing-group tether length. Dative directing-group effects are unexplored with Ti catalysts, and this study demonstrates the potential power of dative substrate-Ti interactions in tuning selectivity.
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