Computational Prediction of Chiral Iron Complexes for Asymmetric Transfer Hydrogenation of Pyruvic Acid to Lactic Acid

Density functional theory calculations reveal a formic acid-assisted proton transfer mechanism for asymmetric transfer hydrogenation of pyruvic acid catalyzed by a chiral Fe complex, FeH[(R,R)-BESNCH(Ph)CH(Ph)NH(2)](η(6)-p-cymene), with formic acid as the hydrogen provider. The rate-determining step is the hydride transfer from formate anion to Fe for the formation and dissociation of CO(2) with a total free energy barrier of 28.0 kcal mol(−1). A series of new bifunctional iron complexes with η(6)-p-cymene replaced by different arene and sulfonyl groups were built and computationally screened as potential catalysts. Among the proposed complexes, we found 1(g) with η(6)-p-cymene replaced by 4-isopropyl biphenyl had the lowest free energy barrier of 26.2 kcal mol(−1) and excellent chiral selectivity of 98.5% ee.