Palladium-Catalyzed Transprotection of Allyloxycarbonyl-Protected Amines: Efficient One-Pot Formation of Amides and Dipeptides

• Published in: Journal of organic chemistry Vol. 60; no. 6; pp. 1733 - 1740
• Main Authors: Roos, Eric C, Bernabe, Pablo, Hiemstra, Henk, Speckamp, W. Nico, Kaptein, Bernard, Boesten, Wilhelmus H. J
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.03.1995; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; TRANSFORMATION; NUCLEOPHILES; TERT-BUTOXYCARBONYL GROUP; TRIBUTYLTIN HYDRIDE; ALLYL; CONJUGATE REDUCTION; CONVERSION; DEPROTECTION; PEPTIDE-SYNTHESIS; DERIVATIVES
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo00111a035

The synthetic utility of the N-(allyloxycarbonyl) (Alloc) substituent in alpha-amino acid derivatives is substantially extended beyond its well-known function as an amine protecting group. When the palladium-catalyzed deprotection is carried out by using tributyltin hydride as nucleophile (the Guibe method) in the presence of an active acylating agent a new acyl group is introduced on nitrogen. Successful acylating agents include carboxylic acid anhydrides, acid chlorides, and activated esters. A useful example of this methodology is the removal of the Alloc group in the presence of tert-butyl dicarbonate, which in essence amounts to a ''transprotection'' to a Boc-protected alpha-amino acid derivative. More importantly, the use of activated N-protected alpha-amino ester derivatives (e.g., pentafluorophenyl esters) leads to dipeptides. This new method for peptide coupling proceeds very fast under mild conditions, in good to excellent yields, and without noticeable racemization.