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

Abstract

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.