Saidykhan Amie, Ebert Jenessa, Fenwick Nathan W, Martin William H C, Bowen Richard D
School of Chemistry and Biosciences, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK.
Molecules. 2025 Apr 18;30(8):1823. doi: 10.3390/molecules30081823.
The rearrangement of a total of 56 members of 22 series of orthogonally protected -alkyl arylsulphonamides of general structure 4-XCHSONRCOR [X = H, CH, F, Cl, Br, CHO, CN, CF or C(CH); R = CH, CHCH, CHCHCH, CH(CH) or CHCH(CH); R = CH, CH or C(CH)] when treated with lithium di-isopropylamide in tetrahydrofuran at -78 °C has been studied. The competition between directed ortho metalated rearrangement, to form 4-X-2-(ROC)CHSONHR and the production of a substituted saccharin, is strongly influenced by the size of R and R, especially in the series with X = CH. When R = CH or to a lesser degree, CH, formation of the saccharin competes to a significant extent, especially when the migrating group is COCH or COCH. In contrast, when R is a larger alkyl group, particularly if it is branched at either the α- or β-carbon atom [CH(CH) or CHCH(CH)], the increased steric hindrance essentially prevents cyclisation, thus facilitating rearrangement to 4-X-2-(ROC)CHSONHR in high yield. The size of the migrating COR group also exerts an effect on the competition between the reactions: when R = C(CH), clean rearrangement is possible even when R = CH in each series of X. These results have implications for further elaboration and rearrangement of 4-X-2-(ROC)CHSONHR in order to prepare substituted saccharins containing a 6-COR group.
研究了通式为4-XCH₂SONRCOR [X = H、CH₃、F、Cl、Br、CHO、CN、CF₃或C(CH₃)₃；R¹ = CH₃、CH₂CH₃、CH₂CH₂CH₃、CH(CH₃)₂或CH₂CH(CH₃)₂；R² = CH₃、CH₂或C(CH₃)₃] 的22个系列共56个正交保护的α-烷基芳基磺酰胺在-78℃下于四氢呋喃中用二异丙基氨基锂处理时的重排情况。定向邻位金属化重排形成4-X-2-(ROC)CH₂SONHR与生成取代糖精之间的竞争受到R¹和R²大小的强烈影响，尤其是在X = CH₃的系列中。当R¹ = CH₃或在较小程度上为CH₂时，糖精的形成在很大程度上存在竞争，特别是当迁移基团为COCH₃或CO₂CH₃时。相反，当R¹是较大的烷基，特别是如果它在α-或β-碳原子处支化 [CH(CH₃)₂或CH₂CH(CH₃)₂] 时，增加的空间位阻基本上阻止了环化，从而有利于高产率地重排为4-X-2-(ROC)CH₂SONHR。迁移的COR基团的大小也对反应之间的竞争产生影响：当R² = C(CH₃)₃时，即使在每个X系列中R¹ = CH₃，也可能实现完全重排。这些结果对于进一步阐述和重排4-X-2-(ROC)CH₂SONHR以制备含有6-COR基团的取代糖精具有重要意义。
