Journal of Organic Chemistry 2013-02-01

Origins of stereoselectivities in chiral phosphoric acid catalyzed allylborations and propargylations of aldehydes.

Hao Wang, Pankaj Jain, Jon C Antilla, K N Houk

Index: J. Org. Chem. 78(3) , 1208-15, (2013)

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Abstract

The chiral BINOL-phosphoric acid catalyzed allylboration and propargylation reactions are studied with density functional theory (B3LYP and B3LYP-D3). Two different models were recently proposed for these reactions by Goodman and our group, respectively. In Goodman's model for allylborations, the catalyst interacts with the boronate pseudoaxial oxygen. By contrast, our model for propargylations predicts that the catalyst interacts with the boronate pseudoequatorial oxygen. In both models, the phosphoric acid stabilizes the transition state by forming a strong hydrogen bond with the oxygen of the boronate and is oriented by a formyl hydrogen bond (Goodman model) and by other electrostatic attractions in our model. Both of these models have now been reinvestigated for both allylborations and propargylations. For the most effective catalyst for these reactions, the lowest energy transition state corresponds to Goodman's axial model, while the best transition state leading to the minor enantiomer involves the equatorial model. The high enantioselectivity observed with only the bulkiest catalyst arises from the steric interactions between the substrates and the bulky groups on the catalyst, and the resulting necessity for distortion of the catalyst in the disfavored transition state.