Versatile chiral bidentate ligands derived from alpha-amino acids: Synthetic applications and mechanistic considerations in the palladium-mediated asymmetric allylic substitutions

A new class of chiral amidine-phosphine hybrid ligands 7a,b, which are read ily accessible from the corresponding alpha-amino acids, were developed, A versatility for construction of new ligands is desirable, by which a variet y of reactions and substrates become applicable. Indeed, a variety of modif ications, such as exchange reactions to other amino groups in the amidine s keleton and the production of other types of ligands, are possible using th e precursor compounds of 7a. Thus, novel chiral ligands 7c,d, 8, 11, and 13 , which provide sterically and electronically different chiral circumstance s, were prepared and used for the palladium-mediated asymmetric allylic sub stitutions of both acyclic and cyclic compounds. In these reactions, high l evels of asymmetric induction were achieved for both substrates. A marked a dvancement of reactivity and enantioselectivity in palladium-catalyzed asym metric allylations of 1,3-diphenylpropen-2-yl pivalate 14a was attained by examination of electronic substituent effects in a new series of chiral P-N and S-N hybrid ligands 8 and 11. Mechanistic views concerning the enantiod iscriminating step were demonstrated, in which a good correlation between a novel Pr/Mr concept and the absolute configuration of allylation products are discussed for the prediction of enantioselecting direction. The use of ketene silyl acetals as nucleophiles was investigated and compared with the corresponding harder anionic carbon nucleophiles. The former nucleophiles afforded higher enantioselectivity in asymmetric allylic transformations of 14a.