Synthesis of Chiral Cyclic Nitrones by Asymmetric Addition of beta-Ketosulfones to Nitroalkenes followed by Reductive Cyclization

The first organocatalytic addition of beta-ketosulfones to nitroalkenes catalyzed by thiourea cinchona alkaloids is presented. The readily obtained addition products were selectively transformed into chiral nitrones by reduction of the nitro group and in situ cyclization (up to 99:1 e.r. and >98:2 d.r.). Moreover, the utility of this method has additionally been demonstrated by the further transformation to functionalized N-hydroxypyrrolidines that possess a quaternary center by addition of trimethylsilyl cyanide (TMSCN) to the C=N bond of the cyclic nitrones in the presence of a Lewis acid.