Computational modelling of the enantioselectivity in the asymmetric 1,4-addition of phenylboronic acid to a bulky, doubly pro-chiral maleimide catalyzed by a Rh/chiral diene complex

Abstract

Computational chemistry is a powerful tool for understanding chemical reactions used for the synthesis of chiral compounds. Here we present a DFT (IEFPCM/PBE0/DGDZVP level of theory) modelling of the stereoselectivity in the Rh-catalyzed 1,4-addition of phenylboronic acid to a bulky maleimide with a chiral diene (Phbod) as the ligand. The substrate is doubly prochiral due to the CC bond and the N-(2-tert-butylphenyl) giving rise to a centre and axial chirality, respectively, upon 1,4-arylation. The predicted absolute configuration was in agreement with the experiment for both diastereomer pairs. Quantitative prediction of the % ee for the major diastereomer was achieved with the M06 functional instead of PBE0 and taking into account all ligand conformations. However, the % ee for the minor diastereomer was always strongly overestimated, implying a possibility for a different, unknown reaction pathway. Applying Boltzmann distribution over all transition state conformers did not improve the accuracy.