3-Phenylphosphaprolines – Synthesis, structure and properties of heterocyclic α-phosphanyl amino acids

Abstract

“Phenylphosphaprolines”, containing trivalent phosphorus within the five-membered ring of proline, were synthesized by cyclocondensation of 2-phenylphosphanyl ethylamines 1a,b with equimolar amounts of glyoxylic acid hydrate (GAH) or pyruvic acid in diethyl ether or 1,4-dioxane. Reaction monitoring revealed primary formation of acyclic intermediates that then converted more (1a) or less (1b) rapidly to the phosphanyl amino acids cis/trans-2a,b or cis/trans-4a,b. Ammonium-ethylphosphonium-bis(glycolate) impurities, e.g. 3b, were formed when an excess of GAH was applied. The conversion of 1a with phenylformic acid via the acyclic precursors 5a and 6a to the heterocyclic product cis/trans-7a was very slow, whereas heating of the mixture in 1,4-dioxane proceeded with decarboxylation to cis/trans-8a. The structures and diastereoisomer ratios of all new compounds were determined by 1H, 31P and 13C solution NMR spectra. The cis/trans-ratio of 2a depends on the synthetic route, i.e. addition of the phosphanylethyl amine 1a to GAH (acidic medium) or of GAH to 1a (basic medium). Furthermore, this ratio changed slowly during storage of the solution of 2a in CD3OD or methanol, indicating ring-opening ring-closure reactions and lower kinetic stability than for proline. XRD analyses established the structures of trans-2a and likewise of trans-4a and trans-8a, which from concentrated solutions crystallized in pure form.