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.

The first template assisted meta-hydroxylation strategy and its use in the synthesis of resveratrol precursor and QR-activity inducer with detailed experimental and in-silico mechanistic understanding.

Strong σ-coordination by a heteroatom containing directing group (DG) is one of the effective strategies for performing site-selective C–H functionalization. Despite tremendous progress in directed ortho-C–H functionalization, selective meta-C–H functionalization using strong σ-coordination remains extremely challenging. Herein, we introduce the 8-nitroquinoline-based DG to ensure the formation of a stable palladacycle which enables selective meta-alkenylation and acetoxylation of arenes. Kinetic experiments, ESI-MS, NMR, and DFT studies provided important information regarding the mechanism of the reaction. The scalability as well as diversification of the products have been examined and are expected to be beneficial in pharmaceutical and material sciences.

Accomplishing high diastereo- and enantioselectivities simultaneously is a persistent challenge in asymmetric catalysis. The use of two chiral catalysts in one-pot conditions might offer new avenues to this end. Chirality transfer from a catalyst to product gets increasingly complex due to potential chiral match-mismatch issues. The origin of high enantio- and diastereoselectivities in the reaction between a racemic aldehyde and an allyl alcohol, catalyzed by using axially chiral iridium phosphoramidites PR/S-Ir and cinchona amine is established through transition-state modeling. The multipoint contact analysis of the stereocontrolling transition state revealed how the stereodivergence could be achieved by inverting the configuration of the chiral catalysts that are involved in the activation of the reacting partners. While the enantiocontrol is identified as being decided in the generation of PR/S-Ir-π-allyl intermediate from the allyl alcohol, the diastereocontrol arises due to the differential stabilizations in the C-C bond formation transition states. The analysis of the weak interactions in the transition states responsible for chiral induction revealed that the geometric disposition of the quinoline ring at the C8 chiral carbon of cinchona-enamine plays an anchoring role. The quinolone ring is noted as participating in a π-stacking interaction with the phenyl ring of the Ir-π-allyl moiety in the case of PR with the (8R,9R)-cinchona catalyst combination, whereas a series of C-H···π interactions is identified as vital to the relative stabilization of the stereocontrolling transition states when PR is used with (8S,9S)-cinchona.

A Pd­(II)-catalyzed protocol for highly regioselective distal γ-C–H silylation and germanylation of aliphatic carboxylic acids is reported. Bidentate 8-aminoquinoline as the directing group was found to stabilize the six-membered palladacycle. A variety of aliphatic carboxylic acids and amino acids were silylated and germanylated in good yields and high diasteroselectivities. Detailed mechanistic studies involving isolation of a Pd­(II) intermediate, determination of the reaction rate and order, control experiments, and isotopic labeling and DFT studies were found to be crucial for elucidating the elementary steps involved in this distal aliphatic functionalization.

We disclose an intriguing and a potentially general role for one of the most commonly used silver salt additives whose molecular understanding continues to remain rather vague in the contemporary practice of palladium catalysis.

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.

The capturing, sequestration and utilization of carbon dioxide have attracted global attention in environment, science and industry. The concurrent conversion of CO2 and CH4 is a reasonable solution to reduce...