One-Pot Synthesis of Phosphanylbis(N-arylglycines) and Spontaneous Diastereoselective Lactamization of P-Alkyl Derivatives To Form Five-Membered P,N-Heterocyclic Amino Acids

• Published in: European journal of inorganic chemistry 2016-07, Vol.2016 (21), p.3417-3422
• Main Authors: Lach, Joanna, Palm, Gottfried J., Jones, Peter G., Heinicke, Joachim W.
• Format: Article
• Language: English
• Subjects: Amino acids; Asymmetry; Coupling (molecular); Derivatives; Hybrid ligands; Hydrates; Isomers; Ligands; Multicomponent reactions; Phosphane ligands; Phosphorus heterocycles; Spontaneous; Stereoselectivity
• ISSN: 1434-1948; 1099-0682
• DOI: 10.1002/ejic.201600202

The one‐pot, three‐component reaction of phenylphosphane with two equivalents each of 4‐acetylaniline and glyoxylic acid hydrate (GAH) in diethyl ether at room temperature furnished phosphanyl‐bis(glycine) 1 as a rac/meso mixture (molar ratio 7:3) whereas condensation of primary alkylphosphanes (cHexPH2, iBuPH2) with p‐toluidine and GAH was followed by additional spontaneous and highly diastereoselective lactamization to form five‐membered P,N‐heterocyclic racemic amino acids 2 and 3. Compound 2, with three centres of asymmetry, displayed only one set of NMR signals, whereas for compound 3 one set was strongly preferred. Crystal structure analysis of 2 confirmed the presence of a racemate, with the asymmetric unit consisting of the 2R,3R,4R isomer; the molecules are linked by hydrogen bonds. The trans(eq‐eq)‐position of the P‐cyclohexyl group towards the substituents at the adjacent C2 and C4 atoms is maintained in [D8]THF solution, as shown by small 2JPH coupling constants. Large 2JPH couplings in compound 3 hint at the opposite preference, i.e. cis orientation, of the less spatially demanding isobutyl group at phosphorus towards the C2 and C4 substituents. The trans isomers of 3 were detected only in trace amounts on the basis of characteristic PCH proton doublets with small 2JPH values. This facile route to novel trialkylphosphane‐type hybrid ligands 2 and 3 may pave the way for further studies of their properties and use as ligands in transition metal compounds and catalysis. PhPH2 reacts with glyoxylic acid hydrate and a primary aniline (1:2:2) in Et2O to afford a rac/meso‐mixture of corresponding phosphanyl‐bis(glycine) 1. Under the same mild conditions, more P‐basic primary alkylphosphanes CyPH2 and iBuPH2, undergo diastereoselective lactamization affording phosphaproline derivatives 2 and 3; the structure of 2 was amenable to X‐ray crystallography.