Computational investigations on the phosphine-ligated CuH-catalyzed conjugate reduction of α-β unsaturated ketones were performed with the DFT method. Two phosphine-ligated CuH catalysts, Ph3P–CuH and (R)-SEGPHOS–CuH, were employed to probe the reaction mechanism with the emphasis on regioselectivity and stereoselectivity. The calculations on the Ph3P–CuH system indicate that there exist two competing reaction pathways: the 1,4- and 1,2-path. The 1,4-path is predicted to be energy-favoured among these reaction paths. The mechanism of the 1,4-path includes two steps: (1) the first step is predicted to be the rate-determining step (RDS), corresponding to the delivery of the hydrogen atom of the CuH catalyst to the β-carbon atom of the substrate, with the formation of the enolate; (2) in the second step, the enolate undergoes a σ-bond metathesis with the hydride source to liberate the final product and regain the catalysts. In the chiral (R)-SEGPHOS–CuH system, the first step of CuH to the unsaturated bond is vital for the distribution of products and therefore responsible for the stereoselectivity of the 1,4-addition. The calculations on the (R)-SEGPHOS–CuH system reproduce the major product in the R-configuration, which is consistent with the experimental observation. The steric hindrance between the bulky substituent moiety of the substrate and the P-phenyl ring of the SEGPHOS–CuH catalyst is identified as the origin of the stereoselectivity for the titled reaction.

Computational investigations on the asymmetric hydrosilylation of acetophenone over ligated CuH catalysts were performed with the DFT method. The calculations predict that the catalytic reaction involves two steps: (1) CuH addition to the carbonyl groupvia a four-membered transition state (TS) with the formation of copper-alkoxide intermediates; (2) regeneration of the ligated CuH catalyst by an external SiH4 through a metathesis process to yield the corresponding silyl ether. The calculations in the chiral diphosphine-ligated CuH systems suggest that the metathesis process is the rate-determining step (RDS). The CuH addition step is vital for the distribution of the racemic products and therefore represents the stereo-controlling step (SCT). In this step, the greater steric hindrance between the aromatic rings of the ligands and the substrate is identified as the major factor for enantioselectivity. The corresponding TS in the face-to-face mode, suffering less steric hindrance, is more stable than its analogue in the edge-to-face mode. The enantioselectivities are calculated to be related not only to the P–Cu–P bite angles in the stereo-controlling TSs, but also to the substituents at the P-aryl rings of the chiral ligands. In short, a larger P–Cu–P bite angle and suitably modified P-aryl rings together are necessary to achieve excellent ee values.

The mechanism of guanidine-catalyzed enantioselective isomerization of 3-alkynoates to allenoates is investigated using density functional theory methods. The calculations predict that the isomerization reaction includes two hydrogen-transfer steps and one conformational change mediated by the TBO catalyst. The first hydrogen-transfer step corresponds to the migration of hydrogen from C4 of the substrate to the guanidine catalyst, and the second one to the transfer of this hydrogen from the guanidine catalyst to C6 of the substrate forming the product. The calculations predict that the first hydrogen-transfer step (deprotonation of the substrate) might be the rate-determining step for the overall reaction. In the chiral system, the evolution of IM1s is crucial for the enantioselectivity of the reaction, which is more relevant to the second hydrogen-transfer step via TS2. In TS2, the N–H⋯O hydrogen bond between the guanidine catalyst and the substrate, sensitive to the chiral environment, might account for the enantioselectivity of the isomerization reaction. The larger size of the substituted group at the chiral site of guanidine could selectively make one of the competing transition states unstable in terms of significantly decreasing the strength of the N–H⋯O hydrogen bond in the disfavored TS, which results in a high ee value.

The mechanism of guanidine-catalyzed enantioselective isomerization of 3-alkynoates to allenoates is investigated using density functional theory methods. The calculations predict that the isomerization reaction includes two hydrogen-transfer steps and one conformational change mediated by the TBO catalyst. The first hydrogen-transfer step corresponds to the migration of hydrogen from C4 of the substrate to the guanidine catalyst, and the second one to the transfer of this hydrogen from the guanidine catalyst to C6 of the substrate forming the product. The calculations predict that the first hydrogen-transfer step (deprotonation of the substrate) might be the rate-determining step for the overall reaction. In the chiral system, the evolution of IM1s is crucial for the enantioselectivity of the reaction, which is more relevant to the second hydrogen-transfer step via TS2. In TS2, the N–H⋯O hydrogen bond between the guanidine catalyst and the substrate, sensitive to the chiral environment, might account for the enantioselectivity of the isomerization reaction. The larger size of the substituted group at the chiral site of guanidine could selectively make one of the competing transition states unstable in terms of significantly decreasing the strength of the N–H⋯O hydrogen bond in the disfavored TS, which results in a high ee value.

Computational investigations on the asymmetric hydrosilylation of acetophenone over ligated CuH catalysts were performed with the DFT method. The calculations predict that the catalytic reaction involves two steps: (1) CuH addition to the carbonyl groupvia a four-membered transition state (TS) with the formation of copper-alkoxide intermediates; (2) regeneration of the ligated CuH catalyst by an external SiH4 through a metathesis process to yield the corresponding silyl ether. The calculations in the chiral diphosphine-ligated CuH systems suggest that the metathesis process is the rate-determining step (RDS). The CuH addition step is vital for the distribution of the racemic products and therefore represents the stereo-controlling step (SCT). In this step, the greater steric hindrance between the aromatic rings of the ligands and the substrate is identified as the major factor for enantioselectivity. The corresponding TS in the face-to-face mode, suffering less steric hindrance, is more stable than its analogue in the edge-to-face mode. The enantioselectivities are calculated to be related not only to the P–Cu–P bite angles in the stereo-controlling TSs, but also to the substituents at the P-aryl rings of the chiral ligands. In short, a larger P–Cu–P bite angle and suitably modified P-aryl rings together are necessary to achieve excellent ee values.