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

Several typical ¹³C‐NMR displacements (of C?O, C(α), C(β), and C_ipso), as well as conformational or energy properties (S? N? C?O dihedral angle, ΔE 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 S?O(2) and H? C(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 MgBr₂. 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 SO₂/C?O syn derivative 10 confirms the predictive validity of our conformational calculations for ΔE≤1.8 kcal/mol.