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The use of more than one catalyst in one-pot reaction conditions has become a rapidly evolving protocol in the development of asymmetric catalysis. The lack of molecular insights on the mechanism and enantioselectivity in dual-catalytic reactions motivated the present study focusing on an important catalytic asymmetric Heck-Matsuda cross-coupling. A comprehensive density functional theory (M06 and B3LYP-D3) investigation of the coupling between a spirocyclic cyclopentene and 4-fluorophenyl diazonium species under a dual-catalytic condition involving Pd2(dba)3 (dba = trans, trans-dibenzylideneacetone) and chiral 2,2'-binaphthyl diamine (BINAM)-derived phosphoric acids (BDPA, 2,2'-binaphthyl diamine-derived phosphoric acids) is presented. Among various mechanistic possibilities examined, the pathway with explicit inclusion of the base (in situ generated sodium bicarbonate/sodium biphosphate) is found to be energetically more preferred over the analogous base-free routes. The chiral phosphate generated by the action of sodium carbonate on BDPA is found to remain associated with the reaction site as a counterion. The initial oxidative addition of Pd(0) to the aryl diazonium bond gives rise to a Pd-aryl intermediate, which then goes through the enantiocontrolling migratory insertion to the cyclic alkene, leading to an arylated cycloalkene intermediate. Insights on how a series of noncovalent interactions, such as C-H···O, C-H···N, C-H···F, C-H···π, lp···π, O-H···π, and C-F···π, in the enantiocontrolling transition state (TS) render the migration of the Pd-aryl to the si prochiral face of the cyclic alkene more preferred over that to the re face are utilized for modulating the enantioselectivity. Aided by molecular insights on the enantiocontrolling transition states, we predicted improved enantioselectivity from 37% to 89% by changes in the N-aryl substituents of the catalyst. Subsequent experiments in our laboratory offered very good agreement with the predicted enantioselectivities.

A mild, asymmetric Heck-Matsuda reaction of five-, six- and seven-membered ring alkenes and aryl diazonium salts is presented. High yields and enantioselectivities were achieved using Pd0 and chiral anion co-catalysts, the latter functioning as a chiral anion phase-transfer (CAPT) reagent. For certain substrate classes, the chiral anion catalysts were modulated to minimize the formation of undesired by-products. More specifically, BINAM-derived phosphoric acid catalysts were shown to prevent alkene isomerization in cyclopentene and cycloheptene starting materials. DFT(B3LYP-D3) computations revealed that increased product selectivity resulted from a chiral anion dependent lowering of the activation barrier for the desired pathway.

Molecular properties and reactions form the foundation of chemical space. Over the years, innumerable molecules have been synthesized, a smaller fraction of them found immediate applications, while a larger proportion served as a testimony to creative and empirical nature of the domain of chemical science. With increasing emphasis on sustainable practices, it is desirable that a target set of molecules are synthesized preferably through a fewer empirical attempts instead of a larger library, to realize an active candidate. In this front, predictive endeavors using machine learning (ML) models built on available data acquire high timely significance. Prediction of molecular property and reaction outcome remain one of the burgeoning applications of ML in chemical science. Among several methods of encoding molecular samples for ML models, the ones that employ language like representations are gaining steady popularity. Such representations would additionally help adopt well‐developed natural language processing (NLP) models for chemical applications. Given this advantageous background, herein we describe several successful chemical applications of NLP focusing on molecular property and reaction outcome predictions. From relatively simpler recurrent neural networks (RNNs) to complex models like transformers, different network architecture have been leveraged for tasks such as de novo drug design, catalyst generation, forward and retro‐synthesis predictions. The chemical language model (CLM) provides promising avenues toward a broad range of applications in a time and cost‐effective manner. While we showcase an optimistic outlook of CLMs, attention is also placed on the persisting challenges in reaction domain, which would optimistically be addressed by advanced algorithms tailored to chemical language and with increased availability of high‐quality datasets. [ABSTRACT FROM AUTHOR]

The integration of machine learning (ML) methods into chemical catalysis is evolving as a new paradigm for cost and time economic reaction development in recent times. Although there have been several successful applications of ML in catalysis, the prediction of enantioselectivity (ee) remains challenging. Herein, we describe a ML workflow to predict ee of an important class of catalytic asymmetric transformation, namely, the relay Heck (RH) reaction. A random forest ML model, built using quantum chemically derived mechanistically relevant physical organic descriptors as features, is found to predict the ee remarkably well with a low root mean square error of 8.0 ± 1.3. Importantly, the model is effective in predicting the unseen variants of an asymmetric RH reaction. Furthermore, we predicted the ee for thousands of unexplored complementary reactions, including those leading to a good number of bioactive frameworks, by engaging different combinations of catalysts and substrates drawn from the original dataset. Our ML model developed on the available examples would be able to assist in exploiting the fuller potential of asymmetric RH reactions through a priori predictions before the actual experimentation, which would thus help surpass the trial and error loop to a larger degree. [ABSTRACT FROM AUTHOR]

The significance of stereoselective C−H bond functionalization thrives on its direct application potential to pharmaceuticals or complex chiral molecule synthesis. Complication arises when there are multiple stereogenic elements such as a center and an axis of chirality to control. Over the years cooperative assistance of multiple chiral ligands has been applied to control only chiral centers. In this work, we harness the essence of cooperative ligand approach to control two different stereogenic elements in the same molecule by atroposelective allylation to synthesize axially chiral biaryls from its racemic precursor. The crucial roles played by chiral phosphoric acid and chiral amino acid ligand in concert helped us to obtain one major stereoisomer out of four distinct possibilities. [ABSTRACT FROM AUTHOR]

The Diels-Alder reactions between variants of 2-trimethylsiloxycyclohexa-1,3-dienes with dienophile (E)-1,4-diphenylbut-2-ene-1,4-dione is described. The findings suggest that the electrostatic interaction between the oxygen lone pairs on the diene and the dienophile is critical to control the selectivity of elements.

Intramolecular nonbonding interactions between chalcogen atoms in a series of ortho substituted arylselenides are quantified. The interaction energies are found to be higher when the thioformyl group acts as the donor and the Se-F bond acts as the acceptor.

The bis-bidentate bridging function of gbha2- with N,O(super -)/N,O(super -) coordination was observed in the complex (mu-gbha)[Ru(super III)(acac)2]2. Density functional theory calculation of (mu-gbha)[Ru(super III)(acac)2]2 yield a triplet ground state with a large (increment of E > 6000 cm(super -1) single-triplet gap.

The synthesis and characterization of a series of organochalcogen(Se, Te) compounds derived from benzyl alcohol are described. Organo dichalcogenides having hydroxy group ortho to selenium/tellurium with weak intramolecular chalcogen...OH interactions is structurally characterized.

The zeolite interior is clearly able to enhance the power of a chiral auxiliary during reaction from excited singlet and triplet states are reported. The cations and confined space force the molecule to adopt a conformation, which results in a stronger interaction between the chiral center and the site of reaction present within a single molecule.