Vesa Nevalainen

Quantum chemical modeling of chiral catalysis. Part 3. On the role of a Lewis basic solvent in the mechanism of catalytic enantioselective reduction of carbonyl compounds by chiral oxazaborolidines

Abstract Structures and energies of formation of complexes of Lewis basic solvents with borane - oxazaborolidine adducts functioning as chiral catalysts were investigated by using ab initio molecular orbital methods (6-31G * //6-31G * ). Formation of complexes of water with a borane adduct of 1,3,2-oxazaborolidine and simpler analogs of it was examined as a model system. Coordination of water to the borane adduct of 1,3,2-oxazaborolidine stabilized the adduct by about 50-60% of that of a free borane. Substitution of water bound to the borane adduct of the catalyst by formaldehyde required about 4 - 5 times more energy than coordination of formaldehyde to the corresponding solvent free borane adduct.

Quantum chemical modeling of chiral catalysis. Part 4. On the hydride transfer in ketone complexes of borane adducts of oxazaborolidines and regeneration of the catalyst

Abstract Hydride transfer and regeneration steps in ketone complexes of borane-oxazaborolidine adducts functioning as chiral catalysts were investigated by using ab initio molecular orbital methods. The hydride transfer was found to be highly exothermic. Formation of a novel 1,3-oxazadiboretane structure was found to precede the regeneration of the catalyst. The regeneration occurring via a cleavage of the 1,3-oxazadiboretane ring was found to require about 10% of the energy released in the hydride transfer. Reactions being potentially involved in the deactivation of oxazaborolidine catalysts were found.

Quantum chemical modeling of chiral catalysis. Part 5 : On the role of alkoxyboranes in the catalytic enantioselective reduction of carbonyl compounds by the CBS method

Abstract Energies of the formation, relative stabilities and structural parameters of alkoxyborane N -adducts of oxazaborolidine type of chiral reduction catalysts were evaluated by means of ab initio molecular orbital calculations. Three models of the oxazaborolidine system were used. Stability of the alkoxyborane adducts and the nature of borane - catalyst interactions was found to depend strongly on the conformation of the alkoxy group. Two different mechanisms for the formation of the alkoxyborane adducts, a direct coordination of an alkoxyborane to the nitrogen of an oxazaborolidine ring and an intramolecular rearrangement of an oxazadiboretane intermediate, are discussed. Properties of borane and alkoxyborane adducts are compared.

Quantum chemical modeling of chiral catalysis. On the mechanism of catalytic enantioselective reduction of carbonyl compounds by chiral oxazaborolidines

Abstract Energies of formation and structural parameters of two model systems of oxazaborolidine type of chiral reduction catalysts (CBS reduction), their borane adducts, and formaldehyde complexes of the borane adducts were calculated by using ab initio molecular orbital methods. Energies of the formation of formaldehyde complexes in which the borane and carbonyl were cis about the BN bond of the oxazaborolidine ring were found to be slightly positive. The corresponding trans coordination was found to be repulsive. A new class of potential chiral catalysts which also contain the substructure OBN was found.

Quantum chemical modeling of chiral catalysis. Part 8. On the conformational freedom of the ketone of ketone-borane complexes of oxazaborolidines used as catalysts in the enantioselective reduction of ketones

Abstract Standard ab initio molecular orbital methods were employed to study conformational freedom of the ketone of ketone-borane complexes of chiral oxazaborolidines used as catalysts for the enantioselective reduction of ketones (CBS reduction). A formaldehyde-borane complex of 1,3,2-oxazaborolidine was used as a model system. A new conformation was found which was energetically more advantageous than the original one predicted by Corey et al. The new conformation was predicted to be destabilized by bulky substituents at the C-5 of the ring. A new class of potential oxazaborolidine catalysts for the enantioselective reduction of ketones was invented.

Quantum chemical modeling of chiral catalysis. Part 2. On the origin of enantioselection in the coordination of carbonyl compounds to borane adducts of chiral oxazaborolidines

Abstract Energies of formation and structural parameters of formaldehyde and acetaldehyde complexes of a model system of borane adducts of oxazaborolidine type of chiral reduction catalysts (CBS reduction) were calculated by using ab initio molecular orbital methods (6-31G*//6-31G*). The energetic preference was determined for the formation of complexes in which the Lewis acidic boron of the borane adduct of an oxazaborolidine would coordinate either syn or anti to the methyl group of acetaldehyde. The formation of anti complex was favored by 15.2 kJ mo −1 which corresponds to a relative anti: syn abundance ratio of 461:1 and an enantiomeric excess of 99.8 %.

Aluminum enolates via retroaldol reaction: catalytic tandem aldol-transfer—Tischtschenko reaction of aldehydes with aldol adducts of ketones to ketones

Abstract Bidentate aluminum chelates derived from biphenol, binaphthol and catechol were found to be efficient catalysts for aldol-transfer reactions of ketone to ketone aldol adducts with aliphatic or aromatic aldehydes giving rise to the formation of aldol adducts of ketones to the aldehydes. In the presence of an excess of an aliphatic aldehyde, a catalytic tandem aldol-transfer—Tischtschenko reaction is observed. The tandem reaction produces monoesters of 1,3-diols with high anti selectivity and with modest to good chemical yield. 1,2-Unsaturated aldehydes are less reactive in the aldol-transfer reaction and require 2–4 times higher load of the catalyst to be used than aliphatic and aromatic aldehydes. Poor diastereoselectivity was observed in the formation of α-substituted aldols and 2-substituted monoesters of anti-1,3-diols indicating that the aldol-transfer reaction is not diastereoselective with the catalysts studied. The utility of the highly 1,3-anti selective formation of diolmonoesters was found to be limited by acyl migration.

Experimental and computational studies on solvent effects in reactions of peracid–aldehyde adducts

Solvent effects on liquid phase oxidation of aldehydes by dioxygen and m-chloroperbenzoic acid were studied experimentally. The main products were the corresponding carboxylic acid and a formate ester formed by Baeyer–Villiger rearrangement. In alcohol solvents (particularly methanol) substantially higher acid to formate ratios were formed than in solvents not capable of forming hydrogen bonds. Formation of both main products can be rationalised via rearrangement reactions of two epimeric peracid–aldehyde adducts, of which the interactions with methanol were studied computationally employing DFT methods at the DNPP level with the Spartan program (v5.0). The calculations indicate that structures of the adducts rearranging to give two equivalents of acid resemble the transition state of the reaction more than structures of the epimeric adducts rearranging to the acid and formate ester in 1:1 ratio. Therefore, the enhanced favor of the formation of acid in the presence of methanol can be explained in the light of Hammonds postulate.

Tandem aldol-transfer–Tischtschenko reaction of aldehydes and β-hydroxyketones catalyzed by trimethylaluminum

Abstract A novel tandem aldol-transfer–Tischtschenko reaction has been developed. It provides a simple one-step synthetic route to diolmonoesters from β-hydroxyketones and aldehydes. The reaction is catalyzed by trimethylaluminum.

Experimental and Computational Studies on Substituent Effects in Reactions of Peracid–Aldehyde Adducts

Abstract Liquid phase oxidation of six branched and four linear aldehydes by dioxygen and m-chloroperbenzoic acid was studied experimentally. 2-Substituted (α-branched) aldehydes reacted to give formates (via Bayer–Villiger mechanism) whereas the related linear saturated aldehydes were converted to the corresponding carboxylic acids. Formation of both these products can be rationalized via rearrangement reactions of peracid–aldehyde adducts 1. Computational studies employing DFT methods at the DNPP level with the Spartan program (v5.0) were carried out in order to understand properties of those adducts. Conformational properties of the adducts 1 were found to shed light on the differences observed in the reactions of linear and branched adducts.