Asymmetric synthesis of 3-substituted γ- and δ-sultams

An efficient and flexible asymmetric synthesis of various 3-substituted gamma- and delta-sultams is described. The key step is a diastereoselective nucleophilic 1,2-addition of various organocerium compounds to the CN double bond of omega-SAMP-hydrazonosulfonates. The resulting hydrazines were obtained in good to excellent diastereomeric excesses (de = 78 to >= 96 %). Removal of the chiral auxiliary by reductive N,N-bond cleavage afforded the corresponding aminosulfonates without racemisation. Ester hydrolysis and subsequent treatment of the resulting sulfonic acids with phosgene in toluene led to the ammosulfonyl chlorides, which were cyclised to the title compounds in good to excellent overall yields (39-51 %) and high enantiomeric excesses (ee = 78-99 %). The absolute configuration was determined by X-ray structure analysis and is in accordance with the postulated mechanism for the diastereoselective 1,2-addition. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006).