4-Substituted norsnoutanones: a new probe system for evaluating electronic effects in π-facial selectivity in nucleophilic additions

Abstract

Remotely substituted norsnoutanone derivatives show significant and consistent p-face selectivity in nucleophilic additions, revealing the interplay of orbital and electrostatic effects.

Face selectivity in electrophilic additions to methylenenorsnoutanes: relative importance of through-space, through-bond and electrostatic interactions

“…These substrates enable a comparison of the effect of two subtly different cyclopropyl units in a truly sterically unbiased environment. This study complements our earlier investigation of nucleophilic additions to the corresponding ketones, 5 in which significant face selectivity was observed and attributed to effective transmittal of orbital and electrostatic effects through three-membered rings. The 9-methylenenorsnoutanes 1b-d, readily synthesized from the corresponding ketones 5 via Wittig olefination (Ph 3 P + MeBr 2 , Bu t OK, 80%), were subjected to dichlorocarbene addition, oxymercuration, epoxidation and hydroboration reactions (Scheme 1).…”

“…This study complements our earlier investigation of nucleophilic additions to the corresponding ketones, 5 in which significant face selectivity was observed and attributed to effective transmittal of orbital and electrostatic effects through three-membered rings. The 9-methylenenorsnoutanes 1b-d, readily synthesized from the corresponding ketones 5 via Wittig olefination (Ph 3 P + MeBr 2 , Bu t OK, 80%), were subjected to dichlorocarbene addition, oxymercuration, epoxidation and hydroboration reactions (Scheme 1). The structures of the E,Z-diastereomers were deduced on the basis of 1 H and 13 C NMR data, but more specifically from (i) the greater deshielding of H-5 in the E-series compared to Z-series, (ii) the relative deshielding of H-2 and H-3 in the Z-series compared to the E-series and (iii) the deshielding of the quaternary C-4 carbon resonances in the Z-series compared to E-series.…”

Electronic Control of Facial Selection in Additions to Sterically Unbiased Ketones and Olefins

“…Because the geometry of a cyclopropyl unit is quite sensitive to substituents, especially π acceptor groups, the possibility of an inherent structural bias in these substrates needs to be considered. However, single-crystal X-ray structure of 43 (R = COOCH 3 ) confirms the isosteric nature of the reaction center 112b. There is neither pyramidalization nor tilt of the carbonyl group in this substrate.…”

“…The observed diastereoselectivities in the reductions of a number of norsnoutanones reveal the profound effect of distal substituents (Scheme ) …”

Face Selection in Addition and Elimination in Sterically Unbiased Systems

“…It should be added at once that extensive and promising efforts have been made in the past few years to fortify the foundations on which these claims are made, and three of them are briefly mentioned here. Adcock et al have published extensive sets of NMR chemical shift data for 5-substituted 2-adamantanones and 2-methyleneadamantanes, and in turn, used these data to distinguish between expectations based on electrostatic and hyperconjugation effects.…”