Title : Synthesis of chiral isoindolinones from chiral (E)-N-(hex-3-en-5-yn-2 yl) propiolamides via a novel Gold-Catalyzed cycloisomerization reaction pathway

Abstract:

method for preparing novel chiral (E)-N-(hex-3-en-5-yn-2-yl)propiolamides 1 and their gold-catalyzed cycloisomerization reactions to give chiral isoindolinones will be presented. Of the gold catalysts screened, μ3-oxotris(triphenylphosphine)trigold(I) tetrafluoroborate, [(Ph3 PAu)3 O]BF4 , proved to be optimal. These cycloisomerization reactions gave cyclized products 2 of unexpected regiochemical outcomes (Scheme). Based on the known reactivity of simple 1,5-enynes the cycloisomerization reactions of (E)-N-(hex-3-en-5-yn-2-yl) propiolamides 1 was expected to first give the lactam intermediate A (Scheme) having a 1,3(Z)-dienyl-5-yne moiety which in principle is set up for a gold-catalyzed (formal [2p+2p+2p]) cyclization reaction to give the 4-substituted isoindolinones B (Scheme). Surprisingly, the products obtained were 6-substituted isoindolinones 2. Deuterium labelling and computational studies revealed a novel cycloisomerization reaction mechanism was operating. The findings from this study and our mechanistic understandings of these cycloisomerization reactions will be presented in this lecture.

Biography:

Prof. Pyne completed his PhD in synthetic organic chemistry in 1979 with Prof. Lew Mander at the Australian National University. After Post-Doc positions with P. Fuchs (Purdue) and E. J. Corey (Harvard University) he was appointed as a Lecturer at the University of Wollongong in 1985. In 1998 he was promoted to full Professor. His recent awards include, the Birch Medal in 2012 from the Royal Australian Chemical Institute (RACI), and the Archibald Ollé Prize for chemical literature from the RACI in 2015. Research fields include organic synthesis (transition metal-catalyzed reactions), natural product synthesis, medicinal chemistry (antibiotics) and phytochemistry.