Flash vacuum pyrolysis of stabilised phosphorus ylides. Part 17. Preparation of aliphatic amino acid derived γ-alkoxycarbonylamino-β-oxo ylides and pyrolysis to give α,β-acetylenic γ-amino acid and GABA analogues

Abstract

A series of eleven α-aminoacyl stabilised phosphorus ylides 9–19 have been prepared by condensation of N-alkoxycarbonyl protected amino acids with Ph₃PCHCO₂Et using a carbodiimide peptide coupling reagent. Upon flash vacuum pyrolysis at 600 °C, these undergo extrusion of Ph₃PO to give the corresponding α,β-acetylenic γ-amino esters 21–29, 33 and 34 in moderate yield. In two cases the terminal alkynes 30 and 31 are also formed. The β-aminoacyl ylide 20 from β-alanine similarly gives the α,β-acetylenic δ-amino ester 35 upon pyrolysis. Regioselective addition of HBr to the triple bond of one acetylenic ester 25 was observed giving a mixture of E and Z α-bromoacrylates 36. Hydrogenation of the N-Cbz acetylenic esters 21–23 and 33 results in N-deprotection and hydrogenation of the triple bond to afford the chiral GABA analogues 37–40 in 70 –>95% ee as determined by ¹⁹F NMR of their Mosher amides. Fully assigned ¹³C NMR spectra of all the ylides and acetylenic ester derivatives are presented.