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.

An increasing number of examples demonstrate that the use of two mutually compatible chiral catalysts in one-pot conditions can help realize the long-cherished goal of simultaneous control of absolute and relative configurations in asymmetric catalysis. Engaging two transition metal catalysts for this goal presents a considerable degree of mechanistic challenge to control the mode of substrate activation as well as origin of enantio- and diastereoselectivities, both of which are central to the burgeoning domain of stereodivergent catalysis. We have employed density functional theory (B3LYP-D3) computations to investigate an important stereodivergent reaction between azaaryl acetamide and cinnamyl methyl carbonate. These compounds participate in the stereocontrolling C–C bond formation in the form of activated substrates, respectively, when bound to chiral Cu-Walphos and Ir-phosphoramidite catalysts. Herein, we provide the molecular origin of how all four stereoisomers of the product bearing two contiguous stereogenic centers could be accessed by changing the combinations of chiral catalysts (C1(R,R p) or C2(S,S p) of Cu-Walphos in conjunction with P1(R,R,R) or P2(S,S,S) of Ir-phosphoramidite catalysts). The origin of stereodivergence is identified to depend on the differences in the number and nature of noncovalent interactions (NCIs) in the stereocontrolling transition states. In particular, NCIs between the chiral catalysts (C–H···π in C1–P1 catalyst dyad and C–H···π, C–H···F, and π···π in C2–P1) in stereocontrolling transition states are found to be the differentiating factors rendering one of the four stereochemically distinct transition states to be the lowest energy one for a given catalyst combination. These molecular insights suggest that subtle modifications to the catalyst framework could be further exploited in stereodivergent catalysis.

This paper reports a series of novel metal acetylacetonates covalently anchored onto amine functionalized silica/starch composite, prepared by the Schiff condensation of metal acetylacetonates [Co(acac) 2 , Cu(acac) 2 , Pd(acac) 2 , Ru(acac) 3 , Mn(acac) 3 , Co(acac) 3 ] with organically modified 3-aminopropyl silica/starch composite. Different metal acetylacetonates have been chosen with a view to select the most active heterogeneous catalyst. Among various catalysts, covalently anchored Cu(acac) 2 onto amine functionalized silica/starch composite [ASS-Cu(acac) 2 ] was found to be the most active and recyclable catalyst for the one-pot thioetherification and one-pot three component synthesis of 2H-indazoles via consecutive C-N and N-N bond formations. All the catalysts were characterized by FTIR, TGA and AAS analysis and the most active catalyst, [ASS-Cu(acac) 2 ] was further characterized by SEM and TEM. The catalyst could be recovered by simple filtration and reused with almost consistent activity for four consecutive runs.

The sense of enantioselectivity in asymmetric dearomative amination of β-naphthols is reported to pivotally depend on the 3,3' substituents on the chiral BINOL-phosphoric acid (CPA) catalysts. The origin of reversal in the sense of stereoinduction from R to S, when the aryl substituent is changed from 3,5-(CF)-CH (CPA-1) to 9-anthryl (CPA-2), has been identified as arising due to the change in the pattern of noncovalent interactions (from predominantly C-H···F to C-H···π interactions) in the stereocontrolling transition states.

Kinetic resolution is a widely used strategy for separation and enrichment of enantiomers. Using density functional theory computations, the origin of how a chiral BINOL-phosphoric acid catalyzes the selective lactonization of one of the enantiomers of α-methyl γ-hydroxy ester is identified. In a stepwise mechanism, the stereocontrolling transition state for the addition of the hydroxyl group to the si face of the ester carbonyl in the case of the S isomer exhibits a network of more effective noncovalent interactions between the substrate and the chiral catalyst.