Steric Effects of -Alkyl Group on the Base-Induced Nitrogen to Carbon Rearrangement of Orthogonally Protected -Alkyl Arylsulphonamides.

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.