Carbonyl Activation by Borane Lewis Acid Complexation: Transition States of H₂ Splitting at the Activated Carbonyl Carbon Atom in a Lewis Basic Solvent and the Proton‐Transfer Dynamics of the Boroalkoxide Intermediate

Abstract

By using transition-state (TS) calculations, we examined how Lewis acid (LA) complexation activates carbonyl compounds in the context of hydrogenation of carbonyl compounds by H in Lewis basic (ethereal) solvents containing borane LAs of the type (C F ) B. According to our calculations, LA complexation does not activate a ketone sufficiently enough for the direct addition of H to the O=C unsaturated bond; but, calculations indicate a possibly facile heterolytic cleavage of H at the activated and thus sufficiently Lewis acidic carbonyl carbon atom with the assistance of the Lewis basic solvent (i.e., 1,4-dioxane or THF). For the solvent-assisted H splitting at the carbonyl carbon atom of (C F ) B adducts with different ketones, a number of TSs are computed and the obtained results are related to insights from experiment. By using the Born-Oppenheimer molecular dynamics with the DFT for electronic structure calculations, the evolution of the (C F ) B-alkoxide ionic intermediate and the proton transfer to the alkoxide oxygen atom were investigated. The results indicate a plausible hydrogenation mechanism with a LA, that is, (C F ) B, as a catalyst, namely, 1) the step of H cleavage that involves a Lewis basic solvent molecule plus the carbonyl carbon atom of thermodynamically stable and experimentally identifiable (C F ) B-ketone adducts in which (C F ) B is the "Lewis acid promoter", 2) the transfer of the solvent-bound proton to the oxygen atom of the (C F ) B-alkoxide intermediate giving the (C F ) B-alcohol adduct, and 3) the S 2-style displacement of the alcohol by a ketone or a Lewis basic solvent molecule.

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

“…Overall, Δ E H and Δ G H consistently indicate the plausibility of the hydrogen‐bonded couples considered herein, and this is in agreement with the aforementioned literature (see Introduction) describing participation of OH⋅⋅⋅O=C bonding motifs in reaction mechanisms. Since association in solvent is quite a complex process, taking the fully separated counterparts as the reference point is a commonly used approach, but it is inherently crude and it can produce an overestimation of the entropy change, Δ S , contributing to the calculated Δ G H ; thus, the magnitude of Δ G H can be substantially underestimated …”

Lewis Acidity of Carbon in Activated Carbonyl Group vs. B(C6F5)3 for Metal‐Free Catalysis of Hydrogenation of Carbonyl Compounds

“…An alternative mechanism for splitting of the H 2 molecule and subsequent facile hydrogenation of carbonyl compounds has been proposed recently. [24][25][26] The mechanism starts with the activation of the C=O group by complexation of a Lewis acid (B(C 6 F 5 ) 3 ) or throughout protonation of the oxygen of the C=O. A ketone sharing a proton with a solvent molecule (solvatedproton) is a common feature of mechanistic consideration in FLP-hydrogenation of carbonyl compounds.…”

“…Quantum chemical calculations showed that upon external activation of the carbonyl group, its Lewis acidity enhances and the carbon atom can behave like a Lewis acidic center to further activate the H 2 molecule in cooperation with solvent as the Lewis base. An alternative mechanism for splitting of the H 2 molecule and subsequent facile hydrogenation of carbonyl compounds has been proposed recently [24‐26] . The mechanism starts with the activation of the C=O group by complexation of a Lewis acid (B(C 6 F 5 ) 3 ) or throughout protonation of the oxygen of the C=O.…”

Aldehyde Reduction by a Pyridone Borane Complex through Boron‐Ligand‐Cooperation: Concerted or Not?

“…[3] A recent computational study reported by Heshmat et al suggests, based on GGA DFT computations, a mechanism for the H 2 splitting in which the carbonyl carbon atom of a ketone coordinated to B(C 6 F 5 ) 3 acts as a Lewis acid in conjunction with an ether molecule of the solvent as a Lewis base. [4] Concerted hydrogenations via a pericyclic six-membered transition state were the generally accepted mechanistic picture for ketone reductions catalyzed by Noyori-type bisphosphinebisamino-ruthenium complexes (Scheme 2). [5] Inspired by these systems, Li et al computationally designed a bifunctional metal-free system, that should, according to the computations, allow concerted hydrogen transfers to carbonyl compounds (Scheme 2).…”

“…Based on DFT computations, Das et al proposed a stepwise mechanism in which the protonation of the ketone by the protonated ether precedes hydride transfer, which is, however, somewhat conflicting with the experimentally determined p K A values of a protonated ether and a protonated ketone . A recent computational study reported by Heshmat et al suggests, based on GGA DFT computations, a mechanism for the H 2 splitting in which the carbonyl carbon atom of a ketone coordinated to B(C 6 F 5 ) 3 acts as a Lewis acid in conjunction with an ether molecule of the solvent as a Lewis base …”