On the Mechanism of Random Handedness Generation in the Reactions of Heterocyclic Aldehydes with Diallylboronates

The mechanism of generation of products with opposite handedness in the reactions of heterocyclic aldehydes with diallylboronates was studied by NMR experiments and DFT computations. The origin of this unusual phenomenon is a competition between monomeric and dimeric autoinductors that promote the formation of opposite enantiomers. Thus, NMR data suggest that racemic alcohol <b>3a</b>, upon dimerization, provides almost exclusively the heterochiral dimeric boronate <b>5a</b>(<i>RS</i>). This corresponds to the computed results predicting strongly exergonic dimerization with ΔΔG²⁹⁸ -6.5 kcal/mol. Dimerization of the chiral boronate <b>3a</b> (<i>R</i>) with 82% ee yields <b>5a</b> (<i>RS</i>) in which all available <b>3a</b>(<i>S</i>) is bound. As a result, 3 species remain in the solution: (1) <b>5a</b>(<i>RS</i>), producing a newly formed racemic product in the reaction with <b>1a</b>, (2) <b>3a</b>(<i>R</i>), reacting with 1a and yielding an <i>R</i>-configured newly formed product, and (3) <b>5a</b>(<i>RR</i>), yielding selectively S-configured newly formed product according to computations. Taking into account the equilibria existing between monomers and dimers, the system is capable of demonstrating the experimentally observed random handedness of the newly formed product.