Internal coordination and solvent effects upon hetero- and homocomplexation of chiral lithium amides: structure reactivity effects

The two chiral lithium amides prepared from (R)-(2-N,N-dimethylamine-ethyl)-(1-phenyl-2-pyrrolidin-1-yl-ethyl)amine (1) and (R)-(2-methoxyethyl)-(1-phenyl-2-pyrrolidin-1-yl-ethyl)amine (2) and n-BuLi, were found to form symmetrically solvated dimers in diethylether (DEE). The addition of tetrahydrofuran (THF) and of 1,3-dimethyl-3,4,5,6-tetrahydro-2-(1H)-pyrimidinone (DMPU) did not affect the 6Li-NMR chemical shift due to a very strong internal coordination. Their reactivity as chiral bases in the desymmetrization of cyclohexenoxide was very low due to this strong entropy driven internal coordination. However, they were found to easily form mixed complexes with n-BuLi which was verified by 13C-NMR and 6Li, 1H-HOESY NMR. One molecule of n-BuLi and one molecule of the chiral lithium amide Li-1 respectively Li-2 constituted the mixed complexes. In this mixed dimer at least one coordination site is available on lithium for coordination of the substrate. The alkylation of benzaldehyde using Li-1/n-BuLi gave 40% and Li-2/n-BuLi gave 30% enantiomeric excess of the (S)-1-phenyl-1-pentanol in very high chemical yields.