Mojgan Heshmat

A Prediction of Proton-Catalyzed Hydrogenation of Ketones in Lewis Basic Solvent through Facile Splitting of Hydrogen Molecules

A ketones carbonyl carbon is electrophilic and harbors a part of the lowest unoccupied molecular orbital of the carbonyl group, resembling a Lewis acidic center; under the right circumstances it exhibits very useful chemical reactivity, although the natural electrophilicity of the ketones carbonyl carbon is often not strong enough on its own to produce such reactivity. Quantum chemical calculations predict that a proton shared between a ketone and the Lewis basic solvent molecule (dioxane or THF) activates carbonyl carbon to the point of enabling a facile heterolytic splitting of H2 . Proton-catalyzed hydrogenation of a ketone in Lewis basic solvent is the result. The mechanism involves the interaction of H2 with the enhanced Lewis acidity of a carbonyl carbon and the free Lewis basic solvent molecule polarizes H2 and enables the hydride-type attack on carbonyl carbon, which is very strongly influenced by the proton shared between a ketone and solvent. The hydride-type attack on carbon is reminiscent of the splitting of H2 by singlet carbenes except that, in this case, a Lewis base from the surrounding environment (solvent) is necessary for polarization of H2 and acceptance of the proton resulting from the heterolytic splitting of H2 .

Water and a Borohydride/Hydronium Intermediate in the Borane-Catalyzed Hydrogenation of Carbonyl Compounds with H2 in Wet Ether: A Computational Study

We have computationally evaluated water as an active Lewis base (LB) and introduced the borohydride/hydronium intermediate in the mechanism of B(C6F5)3-catalyzed hydrogenation of carbonyl compounds with H2 in wet/moist ether. Our calculations extend the known frustrated Lewis pair mechanism of this reaction toward the inclusion of water as the active participant in all steps. Although the definition of the zero-energy point interweaves in comparison of the scenarios with and without water, we will be able to show that (i) water (hydrogen bonded to its molecular environment) can, in principle, act as a reasonably viable LB in cooperation with the borane Lewis acid such as B(C6F5)3 but relatively a strong borane-water complexation can be the hindering factor; (ii) the herein-proposed borohydride/hydronium intermediates with the hydronium cation having three OH···ether hydrogen bonds or a combination of the OH···ether/OH···ketone hydrogen bonds appear to be as valid as the previously considered borohydride/oxonium or borohydride/oxocarbenium intermediates; (iii) the proton-coupled hydride transfer from the borohydride/hydronium to a ketone (acetone) has a reasonably low barrier. Our findings could be useful for better mechanistic understanding and further development of the aforementioned reaction.

Surprisingly Flexible Oxonium/Borohydride Ion Pair Configurations

We investigate the geometry of oxonium/borohydride ion pairs [ether-H(+)-ether][LA-H(-)] with dioxane, THF, and Et2O as ethers and B(C6F5)3 as the Lewis acid (LA). The question is about possible location of the disolvated proton, [ether-H(+)-ether], with respect to the hydride of the structurally complex [LA-H(-)] anion. Using Born-Oppenheimer molecular dynamics and a comparison of the potential and free energies of the optimized configurations, we show that herein considered ion pairs are much more flexible geometrically than previously thought. Conformers with different locations of cations with respect to anions are governed by a flat energy-landscape. We found a novel configuration in which oxonium is below [LA-H(-)], with respect to the direction of borane → hydride vector, and the proton-hydride distance is ca. 6 Å. With calculations of the vibrational spectra of [ether-H(+)-ether][(C6F5)3B-H(-)] for dioxane, THF, and Et2O as ethers, we investigate the manifestation of SSLB-type (short, strong, low-barrier) hydrogen bonding in the OHO motif of an oxonium cation.

Unraveling the Origin of Solvent Induced Enantioselectivity in the Henry Reaction with Cinchona Thiourea as Catalyst

In this work, we report an energy decomposition and electronic structure analysis using DFT calculations for the C-C coupling step in the Henry reaction with cinchona thiourea as catalyst and DMF solvent to unravel the origin of enantioselectivity. We found that the conformation of flexible thiourea moiety is affected by the solvent, and in the preferred conformation of thiourea in strong Lewis basic DMF solvent, the N-H sites are in the opposite direction, i.e., in trans conformation. Hence, the thiourea moiety acts via single hydrogen bonding with substrates. The conformation of the substrates with respect to the forming C-C bond plays critical role to increase orbital interaction between two substrates and enhances hydrogen bond strength between substrates and catalyst, which in turn stabilizes the positive charge developing on the catalyst at the transition state for one of the enantiomers ( S). Thus, the enantioselectivity has electronic structure origin. The stronger H-bond formation in the S enantiomer has been confirmed by the calculated IR spectra and is in agreement with thus far experimental and computational results.

Computational elucidation of a role that Brønsted acidification of the Lewis acid-bound water might play in hydrogenation of carbonyl compounds with H2 in Lewis basic solvent

Brønsted acidification of water by Lewis acid (LA) complexation is one of the fundamental principles in chemistry. Using transition-state calculations (TS), herein we investigate the role that Brønsted acidification of the LA-bound water might play in the mechanism of the hydrogenation of carbonyl compounds in Lewis basic solvents under non-anhydrous conditions. The potential energy scans and TS calculations were carried out with a series of eight borane LAs as well as the commonly known strong LA AlCl3 in 1,4-dioxane or THF as Lewis basic solvents. Our molecular model consists of the dative LA-water adduct with hydrogen bonds to acetone and a solvent molecule plus one additional solvent molecule that participates is the TS structure describing the cleavage of H2 at acetones carbonyl carbon atom. In all the molecular models applied here, acetone (O=CMe2 ) is the archetypical carbonyl substrate. We demonstrate that Brønsted acidification of the LA-bound water can indeed lower the barrier height of the solvent-involving H2 -cleavage at the acetones carbonyl carbon atom. This is significant because at present it is believed that the mechanism of the herein considered reaction is described by the same mechanism regardless of whether the reaction conditions are strictly anhydrous or non-anhydrous. Our results offer an alternative to this belief that warrants consideration and further study.

Theory-based extension of the catalyst-scope in the base-catalyzed hydrogenation of ketones: RCOOH-catalyzed hydrogenation of carbonyl compounds with H2 involving a proton-shuttle

As an extension of the reaction mechanism describing the base-catalyzed hydrogenation of ketones according to Berkessel et al., we use a standard methodology for transition-state (TS) calculations in order to check the possibility of heterolytic cleavage of H2 at the ketones carbonyl carbon atom, yielding one-step hydrogenation path with involvement of carboxylic acid as a catalyst. As an extension of the catalyst scope in the base-catalyzed hydrogenation of ketones, our mechanism involves a molecule with a labile proton and a Lewis basic oxygen atom as a catalyst-for example, R-C(=O)OH carboxylic acids-so that the heterolytic cleavage of H2 could take place between the Lewis basic oxygen atom of a carboxylic acid and the electrophilic (Lewis acidic) carbonyl carbon of a ketone/aldehyde. According to our TS calculations, protonation of a ketone/aldehyde by a proton shuttle (hydrogen bond) facilitates the hydride-type attack on the ketones carbonyl carbon atom in the process of the heterolytic cleavage of H2 . Ketones with electron-rich and electron-withdrawing substituents in combination with a few carboxylic and amino acids-in total, 41 substrate-catalyst couples-have been computationally evaluated in this article and the calculated reaction barriers are encouragingly moderate for many of the considered substrate-catalyst couples.