Water soluble phosphines - Part XIII. Chiral phosphine ligands with amino acid moieties

Nucleophilic phosphination of the potassium or sodium salt of the fluorophe nylalanines (1a, 2a) or -glycines (3a, 4a) with potassium phosphides Ph(R)P K (R = Me, Ph) yields chiral phosphine ligands (1-7) with amino acid moieti es, The X-ray structure of 3 . 2H(2)O (space group Pbca) has been determine d showing a betaine type structure for the amino acid moiety. The alpha-met hyl derivatives of the phosphinophenylglycines (10, 11) were obtained in an analogous manner as 1-7, ortho- and para-Fluoroacetophenones have been emp loyed as starting material for the syntheses of alpha-[4-fluorophenyl]-alph a-methylglycine (9c) and its ortho-isomer (8c). the X-ray structure of its monohydrate has been determined (space group P (1) over bar). The N-acetyl (3b, 8e) and ester derivatives (3d, 8d) of 3 and 8c are accessible using st andard procedures. Resolution of the diastereomeric salt 12 obtained from ( S)-(+)-2-hydroxymethylpyrrolidine and racem-8e by fractionated crystallizat ion yielded the (S,R)-isomer. The absolute configuration of(S,R)-12 was det ermined by X-ray structural analysis (space group P2(1)2(1)2(1)). Cleavage of (S,R)-12 with hydrochloric acid gave enantiopure (R)-8e [alpha](D)(20) = - 30.9 degrees (c = 1, CH3OH). (C) 2000 Elsevier Science S.A. All rights r eserved.