How Borane Reagents Based on α-Pinene Control Stereoselectivity in the Reductions of Carbonyl Groups with Different Stereogenic Elements. 3. The Effect of the Relative Size and Conformation of the Carbonyl Substituents on the Stereoselectivity of the Ipc₂BCl, Eap₂BCl, B-t-Bu-IpcBCl, and B-t-Bu-EapBCl Reagents. A Semiempirical Study

Abstract

The reductions of a more elaborate prostereogenic nonchiral and chiral ketones with the representative borane reagents derived from (+)-alpha-pinene confirm that the overall stereoselectivity, similarly to the previously studied reductions of benzaldehyde and acetophenone, is also controlled, early along the reaction coordinate, by the structure of the borane reagent. The stereoselectivity reflects the energy differences among syn-1, 3-interactions of the smallest of the three boron substituents in the reacting borane conformation with the two carbonyl substituents in the substrate. For the B-alkyl-IpcBCl reagents and the R(S)-CO-R(L) substrates, these are the interactions of the B-Cl with the C-R(S) and C-R(L) bonds. To minimize developing intermolecular syn-1,3-interactions with the reagent's B-Cl bond during the reaction, in the conformationally mobile R(S)-CO-R(L) systems, the R(L) and R(S) groups seek to adopt a more reactive conformation even at the expense of the unfavorable intramolecular interactions.

New Direct 11B NMR-Based Analysis of Organoboranes through Their Potassium Borohydrides

“…While the question as to why the dl form of the reagent is so much more reactive than its meso counterpart was not rigorously addressed, recent semiempirical calculations suggest that these Ipc 2 BCl reductions occur through the reversible formation of a borane−carbonyl complex followed by its collapse through a cyclic “chairlike” transition state . A brief examination of these processes with the meso vs dl suggests that to reach such a transition state, the spectator Ipc group experiences added C-2 Me repulsions with the reacting Ipc group that are absent in the dl reagent.…”

Computational and experimental structure–reactivity relationships: evidence for a side reaction in Alpine-Borane reductions of d-benzaldehydes

“…18–20 Both density functional theory and AM1 transition structures differ from the qualitative structures shown in Figure 1 in one important respect: the six-membered scaffold of atoms that are primarily involved in the reaction coordinate at the transition state form more of a half-chair structure instead of a boat-like arrangement. Even with this important difference, the structures shown in Figure 3 exhibit similar non-bonding interactions as those that might be expected from the qualitative structures in Figure 1.…”