American Chemical Society
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Electronic and Steric Control of Regioselectivities in Rh(I)-Catalyzed (5 + 2) Cycloadditions: Experiment and Theory

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journal contribution
posted on 2010-07-28, 00:00 authored by Peng Liu, Lauren E. Sirois, Paul Ha-Yeon Cheong, Zhi-Xiang Yu, Ingo V. Hartung, Heiko Rieck, Paul A. Wender, K. N. Houk
The first studies on the regioselectivity of Rh(I)-catalyzed (5 + 2) cycloadditions between vinylcyclopropanes (VCPs) and alkynes have been conducted experimentally and analyzed using density functional theory (DFT). The previously unexplored regiochemical consequences for this catalytic, intermolecular cycloaddition were determined by studying the reactions of several substituted VCPs with a range of unsymmetrical alkynes. Experimental trends were identified, and a predictive model was established. VCPs with terminal substitution on the alkene reacted with high regioselectivity (>20:1), as predicted by a theoretical model in which bulkier alkyne substituents prefer to be distal to the forming C−C bond to avoid steric repulsions. VCPs with substitution at the internal position of the alkene reacted with variable regioselectivity (ranging from >20:1 to a reversed 1:2.3), suggesting a refined model in which electron-withdrawing substituents on the alkyne decrease or reverse sterically controlled selectivity by stabilizing the transition state in which the substituent is proximal to the forming C−C bond.