Diastereoselective Alkyl Grignard 1,4‐Additions to para ‐Substituted (2 R )‐ N ‐Cinnamoylbornane‐10,2‐sultam Derivatives: Influence of N‐Atom Pyramidalization

Several typical 13 C‐NMR displacements (of CO, C( α ), C( β ), and C ipso ), as well as conformational or energy properties (SNCO dihedral angle, Δ E syn / anti ; HOMO/LUMO) could be correlated with the electronic parameters of p ‐substituted N ‐cinnamoylbornane‐10,2‐sultams 2 . Even under nonchelating conditions, the pyramidalization of the sultam N‐atom decreases for electron‐attracting p ‐substituents, inducing a modification of the sultam‐ring puckering. Detailed comparison of the X‐ray structure analyses of 2b, 2d , and 2m showed that the orientation of the sterically directing pseudo‐axial SO(2) and HC(2) is modified and precludes any conclusion about the π ‐facial stereoelectronic influence of the N lone pair on the alkyl Grignard 1,4‐addition. We also showed that the aggregating alkyl Grignard reagent may be used in equimolar fashion, demonstrating that the sultam moiety is chelated with a Lewis acid such as MgBr 2 . The Schlenk equilibrium may also be used to generate the appropriate conditions of effective 1,4‐diastereoselectivity. Although the anti ‐s‐ cis / syn ‐s‐ cis difference of conformational energies for N ‐cinnamoyl derivatives 2 is higher than for the simple N ‐crotonoyl analogue, an X‐ray structure analysis of the SO 2 /CO syn derivative 10 confirms the predictive validity of our conformational calculations for Δ E ≤1.8 kcal/mol.