Diastereoselective In and Zn-mediated allylation of pyrazol-4-yl derived (R)-tert-butanesulfinyl imines: synthesis of enantiomerically pure 6-(pyrazol-4-yl)-piperidin-2,4-diones

Abstract The In and Zn-mediated allylation of substituted pyrazol-4-yl derived ( R )- N - tert -butanesulfinyl imines proceeds with high diastereoselectivity depending on the conditions and additives (up to 99.4% de). Thus, the synthesized diastereomeric homoallylsulfinamides were isolated and characterized as pure diastereomers, which were then converted into the corresponding pyrazol-4-yl-derived N -Boc-homoallylamines via consecutive treatment with HCl and Boc 2 O. The latter were then subjected to a sequence of reactions: cyclobromocarbamation with NBS and enolate–isocyanate rearrangement with t BuOK to give novel enantiomerically pure ( S )-6-(pyrazol-4-yl)-piperidine-2,4-diones in 88–96% yield. The absolute configurations of the allylation products were assigned by X-ray single crystal analysis of the intermediate bromomethylurethanes.