Asymmetric alkylation of chiral 2-azapentadienyl metal compounds: Diastereoselective synthesis of alkyl-substituted N′-allylimines (2-aza-1,4-pentadienes)

Article abstract of DOI:10.1002/jlac.199619961117

N-Allylimines (2-aza-1,4-pentadienes) 3 bearing a chiral auxiliary group at C-1 were prepared by a three-step sequence involving condensation of pivaloyl chloride with allylamine, chlorination and reaction with a chiral amine (SMP or SMEMP) as an auxiliary group. Deprotonation of 3 by treatment with butyllithium in tert-butyl methyl ether as solvent at -20°C afforded the chiral 2-azapentadienyllithium compounds 4. Transmetalation of 4a with MgBr₂·Et₂O gave the corresponding magnesium bromide 5. Alkylation with primary alkyl halides is predominantly kinetically controlled and leads to the 3-substituted N-allylimines 6. Secondary and tertiary alkyl halides, however, preferentially give 5-substituted 2-aza-1,3-pentadienes 7. The diastereoselectivity of the alkylation reaction may be increased by transmetalation from the lithium compound to the corresponding magnesium bromide or by exchange of the SMP group for the stronger chelating SMEMP group. The halide ion of the alkylating agent strongly influences the configuration of the newly formed stereogenic center. Thus, the chlorides lead to the opposite stereochemistry compared to the bromides. The effect of different solvents on the regio- and diastereoselectivity of the alkylation reactions was studied. Semiempirical calculations (PM3, MNDO) were used to design a stereochemical model for the metalated intermediates in order to rationalize the stereochemistry observed in the experiments. VCH Verlagsgesellschaft mbH, 1996.