Wasserlösliche Phosohane, XIV. Hydrophile Derivate des Triphenylphosphans mit NH2-, 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 PhPH2 using KOtBu as the base affords the hydrophilic tertiary phosphanes 3 and 4a with terminal CH2-COOH and CH2-NH2 substituents. The corresponding secondary phosphane ligands 2 or 5 may be obtained by Pd-catalyzed P-C coupling of ortho-iodophenylacetic acid with PhPH2 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 Ph2PH gave the esters 7a, 7b. Purification of 7a was achieved via its BH3 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 Me2P(O) analogs 13 and 16 are accessible in a straightforward manner by addition of (MeO)2P(O)H or Me2P(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 Ph3P=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.