Insight Into the Substrate‐Based Influence on the Stereo‐ and Regioselectivity of the Intermolecular Oxidopyrylium (5 + 2) Cycloaddition Reaction

The oxidopyrylium (5 + 2) cycloaddition reaction provides rapid construction of complex bicyclic structures and has proven value within the synthetic organic chemistry community. However, the intermolecular variant of the reaction suffers from various documented challenges, one of which is often low regio‐ and stereoselectivity. We recently reported that oxidopyrylium ylides can react with methyl propiolate to yield 2:1 ylide:methyl propiolate “pincer” cycloadducts with high stereo‐ and regioselectivity. However, depending upon the nature of substitution on the ylide, different regio‐ and stereoisomers are formed. As a result, we found this discovery a valuable starting point for understanding the nuances that dictate the selectivity of oxidopyrylium cycloadditions and embarked on follow‐up studies. The following manuscript describes this work, which leverages a combination of computational and experimental studies to determine that the selectivity of oxidopyrylium pincer cycloadducts is governed by kinetics and is rationalized based upon both sterics and molecular orbital considerations.