A DFT study of the enantioselective reduction of prochiral ketones promoted by pinene-derived amino alcohols

Chiral Aminoalcohols and Squaric Acid Amides as Ligands for Asymmetric Borane Reduction of Ketones: Insight to In Situ Formed Catalytic System by DOSY and Multinuclear NMR Experiments

“…With the aim to better understand the reasons behind the significantly lower enantioselectivity obtained using chiral squaric acid derivatives as ligands compared to the corresponding free chiral aminoalcohols, more detailed studies were performed. According to literature data, different reactive intermediates, as well as monomeric and dimeric oxazaborolidine species, may exist in dynamic equilibrium in the reaction mixture depending on the ligand structure and concentration, type of the solvent and borane reagent [61][62][63][64][65][66][67]. The possible presence of these equilibrating species in situ is a key feature of the catalyst system influencing its performance and activity.…”

3-Amino-2,6,6-trimethylbicyclo[3.1.1]heptan-2-ol

“…12 Although the mechanism of the CBS reduction is well known, a detailed mechanism for the reduction of acetophenone catalyzed by 8a was studied using a DFT method. 13 Enantiomerically pure (1R,2R,3S,5R)-3-amino-pinan-2-ol has been transformed into novel spiroborate esters in reactions with ethylene glycol, propan-1,3-diol, pinacol, catechol, (1S,2S,3R,5S)-pinane-2,3-diol, and (1R,2R,3S,5R)-pinane-2,3-diol. 14 Terpenyl spiroborate esters are prepared in high yields as solids.…”

Insights Into The Origin of Selectivity For [2+2] Cycloaddition Step Reaction Involved In The Mechanism of Enantioselective Reduction of Ketones With Borane Catalyzed By A B-Methoxy Oxazaborolidine Catalyst Derived From (–)-β-Pinene. A DFT And Combined Topological ELF, NCI And QTAIM Study

“…The asymmetric reduction of prochiral ketones catalyzed by chiral oxazaborolidine derived from amino alcohol has been a powerful protocol to induce high enantioselectivety 1,2,3 , where the absolute configuration of the major enantiomer was determined to be R or S under the influence of B and/or N-substitutes as expected for the pathway of the mechanism established by Corey et al 2,4 , which involves the following steps (see Scheme 1): formation of the M2′ active catalyst and the catalyst-borane-ketone adduct M3; proton transfer from the borane moiety to the carbonyl carbon in M3 generates fourmembered ring(B(8)-N(3)-B(4)-O( 7)) at the catalyst-alokoxybotrane adduct M5; formation of the final product (chiral secondary alcohol) and the release of the catalyst. Somewhat surprisingly, several computational studies on the mechanism of the reaction show the change of the selectivity of the oxazaborolydine-borane-ketone adduct complexes in the [2+2] cycloaddition step compared to that obtained in the remained steps involved in the mechanism 5,6 . This finding urged me to disclose certain vital mechanistic insights into this step of the title reaction.…”