Synthesis of a novel type of chiral phosphinocarboxylic acids. The phosphine-palladium complexes catalyzed asymmetric allylic alkylation

Article abstract of DOI:10.1016/S0957-4166(00)86121-2

A novel type of chiral cycloalkylphosphines bearing the carboxy group at the β-position were developed, and used for palladium catalyzed asymmetric allylic alkylation of allylic substrates such as 2-cyclohexenylacetate and 1,3-disubstituted-propenyl acetates (R¹CH=CHCH(OAc)R²:R¹=R²=Ph; R¹=Ph, R²=(CH₂)₄OAc; R¹=Ph, R²=(CH₂)₆OAc; R¹=Ph, R²=(CH₂)₁₀OAc). Reaction of the propenyl acetates with soft carbon nucleophiles such as triethyl sodiophosphonoacetate and sodiomalonic acid esters in the presence of a palladium catalyst prepared in situ from Pd(OAc)₂ and chiral (2-diphenylphospino)cycloalkanecarboxylic acids (7a,b) gave high yields of alkylation products (PhCH=CHCH(X)Ph: > 77%ee for X=CH(CO₂Et)P(O)(OEt)₂ and >72 %ee for X=CH(CO₂Me)₂. The alkylation products 15 and 28a-c were converted into optically active α-methylene-γ-lactone and α-methylene macrolide derivatives. The high stereoselectivity demonstrated by the chiral phosphinocarboxylic acid-palladium catalyzed allylic alkylation suggested to be caused by an electronic repulsion between the carboxy group on the ligand and the incoming soft carbon nucleophile, which directs the nucleophilic attack on one of the π-allyl carbons.