A novel multistep mechanism for the stereocontrolled ring opening of hindered sulfamidates: Mild, green, and efficient reactivity with alcohols

Resumen

Cyclic hindered sulfamidates exhibited an outstanding performance in their ring-opening reactions with alcohols and in the absence of any external activator. The mechanism of this unprecedented transformation was thoroughly studied both experimentally and theoretically. As a result, a nontrivial stepwise pathway involving solvent-induced conversion of the sulfamidates to activated aziridinium and then to oxazolinium cations, which are finally opened at their 5-position with inversion of configuration, is proposed. The presence of the SO 3 moiety in the sulfamidate was revealed as a "built-in activator". In fact, the spontaneous SO 3 cleavage takes place under the reaction conditions and avoids the subsequent step of hydrolysis after the ring opening of the sulfamidates. This is another important improvement of this meth-odology with respect to the standard basic conditions, allowing a greater compatibility with other functional groups. Furthermore, the carbamate group plays a key role in this mechanism. Briefly, a highly chemoselective and stereoespecific formal solvolysis of hindered sulfamidates with alcohols without further activation is described. This reaction takes place exclusively at the quaternary center with inversion of configuration, providing a new straightforward synthetic route to O-substituted α-methylisoserines. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.