Origin of diastereoselectivity in the thermal [4+2] cycloadditions of dienophiles derived from Oppolzer's sultams: Steric vs. Stereoelectronic Influences

Abstract

Comparative semi‐empirical PM3 and ab initio STO 3‐21G calculations on bornanesultam‐derived dienophiles containing the structural moiety SO2NC(O)X(α) = Y(β) suggest that, among the conformers of low energy, the thermodynamically less stable SO2/C(O)‐syn,C(O)/X=Y‐s‐cis conformation is also reactive in terms of LUMO level and atomic coefficients. Furthermore, the X(α), Y(β) LUMO atomic coefficients are nonequivalent with respect to both X(α)‐re and X(α)‐si faces, and thus have, depending on the conformation, a matching or mismatching stereoelectronic influence with the co‐operative steric effect. This dissymmetry is believed to result from the generalized anemone effect of the N lone pair, itself anomerically stabilized and directed, in the absence of crucial steric interactions, by the pseudo‐axial anti‐periplanar SO bond. Five N‐acyl‐substituted bornanesultams arc discussed ((–)‐1a: N‐acryloyl, XCH, YCH2; (–)‐1b; N‐crotonoyl, XCH, YCHMe; (–)‐1c: N‐N′‐fumaroyl, XCH, YCH(C(O)‐bornanesultam); 2a: N‐glyoxyloyl, XCH, YO; 2b: N‐acylnitroso, XN, YO). In this context, differences with toluenesultams 3 are pointed out. A previous report on N‐(acylnitroso)‐bornanesultam 2b is revisited, and the diastereoselectivity observed is shown to result from thermodynamic control.

X‐Ray Structure Analyses of Alkyl‐Substituted N‐Acryloyl‐ and N‐Crotonoyltoluenesultams

“…This hypothesis better explains the observed stereoselectivity by competition with an anti-s-cis C(n)-re approach on the sterically more hindered face, shie!ded by the pseu- ' ) For more precise PM3 calculations of [4 + 21 transition states of (-)-la, see [9]. lo) We believe that the stereoelectronic interaction is weaker than the steric interaction on the basis of the absorption.…”

“…[5]; -6.1(8)" [6]). Oppolzer had suggested that the twisting of the dienophile around this bond might be important for the stereocontrol IS] [I 11, although no evidence of this influence could be found by recent PM3 calculations [9].…”

“…') For a rationalization of the high diastereoselectivity observed in the presence of hypothetically unchelated dicoordinated (-)-la during its [4 + 21 cycloaddition to cyclopentadiene, see [9].…”

“…' ) For PM3 calculations showing the higher reactivity of the syn-s-cis conformer during the [3 + 21 cycloaddition of (-)-la, see footnote 41 in [9]. This hypothesis better explains the observed stereoselectivity by competition with an anti-s-cis C(n)-re approach on the sterically more hindered face, shie!ded by the pseu- ' ) For more precise PM3 calculations of [4 + 21 transition states of (-)-la, see [9].…”

“…We thought it useful to present the crystallographic structure analyses of (-)-la and ( +)-lb4), in view of their very recently outlined structural differences with (-)-2a,b [9]. …”