L-Cysteine-, L-Methionine-, and D-Penicillamine-Derived Ligands for Transition Metal Catalyzed Carbon-Carbon Bond-Forming Reactions.

Article abstract of DOI:10.1021/jo00218a004

Synthetic methods are described for the conversion of L-cysteine, L-methionine, and D-penicillamine to S-alkylated dimethylamino alcohols derived by, respectively, alkylation of sulfur and nitrogen followed by reduction of the carboxyl group.One-pot mesylation followed by treatment with lithium diphenylphosphide provides the corresponding phosphine derivative, 2-(dimethylamino)-1-(diphenylphosphino)-3-(methylthio)propane (cysphos), the S-isopropyl derivative (isopropylcysphos), 2-(dimethylamino)-1-(diphenylphosphino)-4-(methylthio)butane (methphos), and 2-(dimethylamino)-1-(diphenylphosphino)-3-methyl-3-(methylthio)butane (penphos).The latter ligand had an enantiomeric excess of 82percent, whereas the other ligands are enantiomerically pure.These compounds have been used as ligands for solubilization of catalytic amounts of NiCl2, which is used to mediate the coupling of vinyl bromide with the (racemic) Grignard reagent of 1-phenyl-1-chloroethane.The coupling product, 3-phenyl-1-butene, is formed in excellent yields and with enantiomeric excesses of up to 65percent (methphos).In addition the cross coupling of vinyl bromide to the Grignard reagent of 2-octyl chloride has also been examined; enantiomeric excesses of 3-methyl-1-nonene of up to 18percent are obtained (penphos).Some comments regarding mechanism and the possible effect of the sulfur heteroatom are made.In addition it is shown that the method of preparation of the Grignard reagent and the concentration thereof are important considerations for the overall enantiomeric excess of the derived coupling product.