Stereoselective Synthesis of Unsaturated and Functionalized l‑NHBoc Amino Acids, Using Wittig Reaction under Mild Phase-Transfer Conditions

• Published in: Journal of organic chemistry Vol. 77; no. 17; pp. 7579 - 7587
• Main Authors: Rémond, Emmanuelle, Bayardon, Jérôme, Ondel-Eymin, Marie-Joëlle, Jugé, Sylvain
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 07.09.2012
• Subjects: Aliphatic compounds; Amino Acids - chemical synthesis; Amino Acids - chemistry; Chemistry; Exact sciences and technology; Molecular Conformation; Organic chemistry; Peptides; Phase Transition; Preparations and properties; Stereoisomerism; Phase transfer reaction; Nitro compound; Nitrile; Peptides; Tertiary phosphine; Weak base; Deprotection; Palladium complex; Liquid phase; Triphenylphosphine; Iodine Organic compounds; Metallocene; Phosphorus Organic compounds; Unsaturated compound; Stereoselectivity; Organic iodine compounds; Amine; Aminoester; Functionalization; Carboxylic acid; Aspartic acid; Aromatic compound; Chemical synthesis; Wittig reaction; Catalytic reaction; Melting; Chemical reagent; Organic azide; Aliphatic compound; Aldehyde; Dienic compound; Phosphonium; Iron Organic compounds; Potassium phosphate; α-Aminoacid; Aminoacid; Addition reaction; Fluorine Organic compounds; Solid phase; Chloro-benzene
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo3013622

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 K3PO4 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.