Hypercoordinate iodine for catalytic asymmetric diamination of styrene: insights into the mechanism, role of solvent, and stereoinduction.

Hypercoordinate iodine has evolved as an impressive class of catalysts for various organic transformations. Extension of this idea to asymmetric applications, such as in the asymmetric difunctionalization of styrene or its derivatives, constitutes an important reaction. In this study, the mechanism and origin of stereoinduction in styrene diamination, with a sulfonimide (HNMs2) as the diaminating agent and iodoresorcinol (((iPr)2N(CO)-CH(Me)-O)2Ar-I) based chiral hypercoordinate iodine as the catalyst, are investigated using density functional theory calculations. The energetically preferred catalytic pathway has been found to involve, among other steps, two very important mechanistic events: (a) the formation of a catalyst-substrate complex by the action of styrene on the catalyst ArI(NMs2)2, resulting in the displacement of one of the imidates (NMs2 -); and (b) a rebound of the departed imidate on the iodine-bound styrene to form an iodonium ion intermediate with a N-C bond. Explicit interaction of the imidate ion with hexafluoroisopropanol (HFIP), used as a solvent additive, lowers the barrier for the formation of the iodonium ion. The P helical fold of the chiral arms of the iodoresorcinol catalyst is found to offer a chiral environment for the reactants. Coordination of the iodine catalyst to the styrene double bond is found to make the benzylic carbon more electrophilic and hence makes it the preferred site for the nucleophilic addition. In the chiral environment of the catalyst, an enhanced polarization of the styrene double bond is noticed when the double bond coordinates through the si prochiral face than the re face. Nucleophilic addition on the re face of the catalyst-substrate complex is associated with a lower activation barrier leading to the experimentally observed S enantiomeric product. The stereoselective model developed in this study can be employed to related asymmetric styrene difunctionalizations using similar hypercoordinate iodine catalysts.

On the activation of hypercoordinate iodine(iii) compounds for reactions of current interest.

Central to the reactivity of hypercoordinate iodine as a continually emerging compound for organic transformation is its activation by various additives. We wish to present the current understanding on bonding and activation modes under different reaction conditions involving hypercoordinate iodine(iii) compounds.

Machine learning for predicting product distributions in catalytic regioselective reactions.

Gaining predictable control over various forms of selectivities, such as enantio- and/or regio-selectivities, has been a long-standing goal in chemical catalysis. Although a number of factors such as the molecular features of the reactants and catalysts, as well as the reaction conditions, can influence the outcome of a reaction, it is not quite conspicuous as to what combinations of these parameters would offer a desired form of selectivity. We use machine learning tools, such as the neural network (NN), decision tree (DT), logistic regression (LR) and Random forest algorithms, to (a) analyze the outcome of an important catalytic regio-selective difluorination reaction of alkenes, and (b) decipher the complex interplay of various molecular parameters and their non-linear dependencies. The connection between what features of alkenes will yield 1,1-difluorination and how subtle changes would steer the reaction to 1,2-difluorination under identical conditions is enunciated. The NN was able to accurately predict whether a given alkene would yield a 1,1- or 1,2-difluorinated product. A combination of DT and the random forest classifier offered important chemical insights, which could be used in making a more rational choice of the reactant alkene for the desired regioisomeric product. The results could have far reaching implications in predicting which regioisomer is likely to be formed under a given set of conditions, and thus this technique is capable of expediting the development of catalytic transformations.

Transposed Paternò-Büchi Reaction.

A complementary strategy of utilizing ππ* excited state of alkene instead of nπ* excited state of the carbonyl chromophore in a "transposed Paternò-Büchi" reaction is evaluated with atropisomeric enamides as the model system. Based on photophysical investigations, the nature of excited states and the reactive pathway was deciphered leading to atropselective reaction. This new concept of switching of excited-state configuration should pave the way to control the stereochemical course of photoreaction due to the orbital approaches required for photochemical reactivity.

Mechanistic insights on iodine(III) promoted metal-free dual C-H activation involved in the formation of a spirocyclic bis-oxindole.

The mechanism of a metal-free, phenyliodine(III) bis(trifluoroacetate) promoted, dual aryl C-H activation of an anilide to a spirocyclic bis-oxindole is examined using density functional theory (M06-2X). The most preferred pathway proceeds through the involvement of a novel iodonium ion intermediate and a pivotal trifluoroacetate counterion. The two sequential aryl C-H activations, assisted by trifluoroacetate as well as the superior leaving group ability of PhI, facilitate the formation of spirocyclic bis-oxindole.

Noninnocent role of N-methyl pyrrolidinone in thiazolidinethione-promoted asymmetric aldol reactions.

The origin of stereoselectivity in the reaction between α-azido titanium enolate derived from chiral auxiliary N-acyl thiazolidinethione and benzaldehyde is established using the DFT(B3LYP) method. A nonchelated transition state with N-methyl-2-pyrrolidinone (NMP) bound to a TiCl(3) enolate is found to be energetically the most preferred model responsible for the formation of an Evans syn aldol product. The TS model devoid of NMP, although of higher energy, is found to be successful in predicting the right stereochemical outcome.