Deuterium Isotope Effects in the Reduction of Cyclohexanones. The Concepts of Steric Approach Control and Product Development Control

Abstract

Definitions for the terms steric approach control and product deuelopment control in relation to the degree of bonding in the transition state are put forward. Kinetic deuterium isotope effects in the reduction of a graded series of ketones by NaBH, and NaBD, have been measured. These effects are inverse, and show no systematic dependence on the degree of steric hindrance of the ketone. This evidence appears to invalidate the steric approach control-product development control explanation of the axial to equatorial product ratios (1). The primary isotope effect is very small, which is consistent with an early transition state in these reductions, as demanded by other explanations of product ratios, but since several other factors causing small isotope effects may be applicable, the evidence does not constitute proof of an early transition state.The main conclusions of this work have already been published in preliminary form (2).Les notions de "steric approach control" et 'kroduct deuelopment control" en relation avec le degri. de liaison dans I'ttat de transition, sont precisees. Les effets isotopiques du deuterium sur la cinbtique de reduction d'une serie de cetones par NaBH, et NaBD,, ont Ct C mesurts. Ces effets sont inverses et ne montrent aucune dependance systematique avec le degrt d'empschement sttrique de la cCtone. Cette mise en evidence montre que I'explication des rapports du produit axial et equatorial par le "steric approach control" et "product development control", n'est pas valable (1). L'effet isotopique primaire, trts faible, est compatible avec un debut d'6tat de transition dans ces rbductions. Ce rbsultat, deji mentionnt dans d'autres etudes, ne constitue pas une preuve puisque de nombreux autres facteurs peuvent Etre la cause de ces faibles effets isotopiques. Les conclusions principales de ce travail ont deja Ct C publikes dans une note preliminaire (2).

Substituent effects in reductions of heteroaromatic cations

“…In this work we determined kinetic isotope effects for the borohydride reductions of the least reactive cation in each of the series 1 (X = O, S and NMe) and found k BH 4 /k BD 4 (25°C) = 1.25, 1.63 and 0.94, respectively. These values are similar to those found for other borohydride reductions 34 and are also believed to be consistent with early transition states.…”

Reactions of Allylmagnesium Reagents with Carbonyl Compounds and Compounds with C═N Double Bonds: Their Diastereoselectivities Generally Cannot Be Analyzed Using the Felkin–Anh and Chelation-Control Models

“…Steric approach control, however, does not assume a Curtin–Hammett kinetic scenario. Instead, it focuses on what steric interactions develop upon bringing a reagent close to the starting material. , Such steric interactions in the transition state can be sufficient to define selectivity. It is correct that steric approach is involved in the other modes of stereocontrol as well (as in determining which face is attacked once chelation had occurred or what interactions occur in the Felkin–Anh transition state once orbital interactions are optimized), but steric approach control requires only steric factors developing between the components of a reaction to explain selectivity.…”

New Taxane Derivatives: Synthesis of Baccatin[14,1-d]furan-2-one Nucleus and Its Condensation with the Norstatine Side Chain

“…Unlike the reduction of 13-oxobaccatin III 1,14-carbonate, which gave a mixture of 13α- (major stereomer) and 13β-hydroxybaccatin III derivatives, only the single 13α-hydroxy epimers (i.e., 5 from 4 and 9/10 from 8 ) were isolated. A favored approach of the hydride ion from the less hindered β-face of the C-13 keto group of the folded structure of the taxane skeleton, or the double bond of the lactone ring, well accounts for such selectivity. , In the present case, the presence of the furanone ring increased the steric demand, thus allowing a high steric control in the reduction process. Furthermore, the α-OH isomers are probably the more thermodinamically stable compounds, as evinced when an equilibration occurred between 6 and 5 (see below, Scheme ).…”