The stereoselective synthesis of a new amino acid phosphonium salt was described by quaternization of melting triphenylphosphine with the γ-iodo NHBoc-amino ester, derived from L-aspartic acid. The deprotection of the carboxylic acid function to afford the phosphonium salt with a free carboxylic acid group was achieved by a palladium-catalyzed desallylation reaction. This phosphonium salt was used in the Wittig reaction with aromatic or aliphatic aldehydes and trifluoroacetophenone, under solid-liquid phase-transfer conditions in chlorobenzene and in the presence of K(3)PO(4) as weak base, to afford the corresponding unsaturated amino acids without racemization. Thus, the reaction with substituted aldehydes allows to graft various functionalized groups on the lateral chain of the amino acid, such as trifluoromethyl, cyano, nitro, ferrocenyl, boronato, or azido. In addition, the reaction of the amino acid Wittig reagent with α,β-unsaturated aldehydes leads to amino acids bearing a diene on the lateral chain. Finally, this amino acid phosphonium salt appears to be a new powerful tool for the preparation of unsaturated and non-proteinogenic α-amino acids, directly usable for the synthesis of customized peptides.

The first P-chirogenic aminophosphane-phosphinite (AMP*P) ligand (4a) supported on the upper rim of a calix [4]arene moiety was synthesized in two steps using the ephedrine methodology. Ligand 4a was used for the preparation of the corresponding rhodium complex [Rh(COD)-(AMP*P)]BF 4 (5a) (COD=1,8-cyclooctadienyl), which was tested for asymmetric catalyzed hydrogenation of various substrates. The structures of the AMP*P ligand as diborane and rhodium complexes 3a and 5a were established by X-ray analysis. The asymmetric hydrogenation catalyzed with the Rh complex 5a exhibits excellent enantioselectivities up to 98%. Investigation of modified P-chirogenic aminophosphane-phosphinite ligands 4b,c, bearing an isoelectronic or a sterically similar substituent on the P-chirogenic aminophosphane unit, demonstrates that the calix[4]arene substituent of the aminophosphane moiety plays a major role in the better asymmetric induction. The enantioselectivity of the catalyzed hydrogenation was weakly influenced by the hydrogen pressure, which is in good agreement with a stereodetermining step involving the substrate-rhodium complexes. Computer modeling indicated the presence of two conformers for the active AMP*P rhodium species, according to whether the rhodium metal is outside or inside the calix[4]arene cavity (called outer and inner). It is obvious that the complexation of the substrate with the active rhodium species forces this complex to adopt fully the outer conformation and hence explains why the calixarene fragment plays a key role in the stereodetermining step. † This paper is dedicated to Prof. H. Kagan for his 80th birthday.