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
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.