Design of asymmetric catalysts generally involves time- and resource-intensive heuristic endeavors. In view of the steady increase in interest toward efficient catalytic asymmetric reactions and the rapid growth in the field of machine learning (ML) in recent years, we envisaged dovetailing these two important domains. We selected a set of quantum chemically derived molecular descriptors from five different asymmetric binaphthyl-derived catalyst families with the propensity to impact the enantioselectivity of asymmetric hydrogenation of alkenes and imines. The predictive power of the random forest (RF) built using the molecular parameters of a set of 368 substrate–catalyst combinations is found to be impressive, with a root-mean-square error (rmse) in the predicted enantiomeric excess (%ee) of about 8.4 ± 1.8 compared to the experimentally known values. The accuracy of RF is found to be superior to other ML methods such as convolutional neural network, decision tree, and eXtreme gradient boosting as well as stepwise linear regression. The proposed method is expected to provide a leap forward in the design of catalysts for asymmetric transformations.

N-heterocyclic carbenes (NHCs) belong to the popular family of organocatalysts used in a wide range of reactions, including that for the synthesis of complex natural products and biologically active compounds....

A catalytic system for intramolecular C(sp2)–H and C(sp3)–H amination of substituted tetrazolopyridines has been successfully developed. The amination reactions are developed using an iron-porphyrin based catalytic system. It has been...

Current developments in the burgeoning area of cooperative asymmetric catalysis indicate the use of N-heterocyclic carbenes (NHCs) in conjunction with other catalysts such as a Brønsted acid. Herein, mechanistic insights derived through a comprehensive DFT (M06-2X) computational study on a dual catalytic reaction between an enal and an imine leading to trans-γ-lactams, catalyzed by a chiral NHC and benzoic acid, is presented. In the most preferred pathway, we note that the NHC catalyst activates one of the reactants (enal) in the form of a Breslow intermediate, whereas the electrophilic partner (imine) is activated by the benzoic acid through protonation of the imino nitrogen. In this article, we focus on the origin of cooperative action of both catalysts as well as on the stereoselectivity by identifying the stereocontrolling transition states. The explicit and cooperative participation of the Brønsted acid and NHC lowers the energetic barrier both in the Breslow intermediate formation and in the stereocontrolling step through a number of C–H···π, N–H···O, and π···π noncovalent interactions. The enantio- and diastereoselectivities computed using the transition state models with an explicit benzoic acid are in good agreement with the earlier experimental reports.