Wasserlösliche Phosohane, XIV. Hydrophile Derivate des Triphenylphosphans mit NH_2-, COOH- und P(O)(OR)₂-funktionalisierten Seitenketten / Water Soluble Phosphanes, XIV. Hydrophilic Derivatives of Triphenylphosphane with NH₂, COOH and P (O)(OR)₂ Functionalized Side Chains

Abstract

Nucleophilic phosphanylation of ortho-fluorophenylacetic acid or ortho-fluorobenzylamine with PhPH 2 using KOtBu as the base affords the hydrophilic tertiary phosphanes 3 and 4a with terminal CH 2 -COOH and CH 2 -NH 2 substituents. The corresponding secondary phosphane ligands 2 or 5 may be obtained by Pd-catalyzed P-C coupling of ortho-iodophenylacetic acid with PhPH 2 or selective nucleophilic phosphanylation of ortho-fluorophenylacetic acid. Novel phosphonatomethyl derivatives 7a, 7b of triphenylphosphane have been obtained in a two stage synthesis using ortho-iodobenzylchloride or meta-iodobenzylbromide as starting materials. Arbusov reaction with P(OEt) 3 and Pd-catalyzed P-C coupling reactions with Ph 2 PH gave the esters 7a, 7b. Purification of 7a was achieved via its BH 3 adduct 8a. Deprotection, hydrolysis and neutralisation with NaOH affords the water soluble sodium salts 9a,9b. α-Hydroxy and α-benzylamino derivatives 12 and 14 of ortho-diphenylphosphanobenzyl phosphonate (e.g. 7a) and the corresponding Me 2 P(O) analogs 13 and 16 are accessible in a straightforward manner by addition of (MeO) 2 P(O)H or Me 2 P(O)H to ortho-phosphanobenzaldehyde 11a or its benzaldimino derivative 15, respectively. An improved synthesis for 11a -11c has been developed. Reaction of 11a with the Wittig reagent Ph 3 P=C(H)COOEt and subsequent hydrolysis of the intermediate ester 17a affords ortho-diphenylphosphano cinnamic acid 17. The catalytical activity of 1,9a, 9b and related ligands in Suzuki-type coupling reactions has been investigated.