Chiral pyrrolidine thioethers: effective nitrogen-sulfur donating ligands in palladium-catalyzed asymmetric allylic alkylations

Enantiomeric cyclic, five-melnbered alcohols and tic-diols were converted into the corresponding mono- and bis(aryl-sulfanyl) derivatives with complete inversion of configuration at one or both stereogenic centers. The thus obtained chiral thioethers were tested in the Pd-catalyzed allylic alkylation of dimethyl malonate with rac-1,3-diphenyl-2-propenyl acetate. The purely S,S-donating C-2-symmetric chiral ligands showed poor to moderate enantioselectivity (up to 42%), while 1-alkyl-3,4-bis(aryl-thio)pyrrolidines afforded much higher results, 81-89% ee. When chiral pyrrolidine mono-thioethers were applied the observed enantioselectivity improved further to 86-90% ee. These results suggest that the pyrrolidine thioethers served as the N(sp(3)),S-donating chiral ligands. Examination of molecular models showed that the sense of stereoinduction, namely (R)-product from with (3R)-1-benzyl-3-(arylthio)pyrrolidine is in agreement with the nucleophilic attack being directed at the allylic carbon located trans to the sulfur atom in the intermediate eta(3)-allylpalladiuln complex. (C) 2004 Elsevier Ltd. All rights reserved.