1,3-Asymmetric Induction in Diastereoselective Allylations of Chiral N-Tosyl Imines

Lewis-acid mediated allylations of β-alkoxy N-tosyl imines lead to 3-alkoxy homoallylic N-tosyl amines with anti diastereoselectivity. Diastereoselectivity and yields of reactions are comparable between two methods of Hosomi-Sakurai allylations. Observed selectivity trends and computational evidence suggest that 1,3 asymmetric induction occurs through the formation of a six- membered ring chelate which adopts a half-chair-like conformation. The product ratios of allylations to β-alkoxy N-tosyl imines are dependent on conformation preferences of the chelate and stereoelectronic interactions in the transition-state structures. Debenzylation and detosylation of these allylation products result in anti 1,3-amino alcohols, a privileged motif in synthetic and natural bioactive compounds.

Strong hyperconjugative interactions limit solvent and substituent influence on conformational equilibrium: the case of cis-2-halocyclohexylamines

The presence of strong stereoelectronic interactions involving the substituents in cis-2-substituted cyclohexanes may lead to results different from those expected. In this work, we studied the conformational behavior of cis-2-fluoro- (F), cis-2-chloro- (Cl), cis-2-bromo- (Br) and cis-2-iodocyclohexylamine (I) by dynamic NMR and theoretical calculations. The experimental data pointed to an equilibrium strongly shifted toward the ea conformer (equatorial amine group and axial halogen), with populations greater than 90% for F, Cl and Br in both dichloromethane-d 2 and methanol-d 4. Theoretical calculations (M06-2X/6-311++G(2df,2p)) were in agreement with the experimental, with no influence of the solvent or the halogen on the equilibrium. A principal component analysis of natural bond orbital energies pointed to the σ*C–X and σC–H orbitals and the halogen lone pairs (LPX) as the most significant for the hyperconjugative interactions that influenced the equilibrium. The σC–H → σ*C–X hyperconjugation and the interactions involving the LPX counterbalance each other, explaining the non-influence of the halogen on the conformational equilibrium. These interactions are responsible for the strong preference for the ea conformer in cis-2-halocyclohexylamines, being strong enough to restrain the shift in the equilibrium due to other factors such as steric repulsion or solvent effects.