2-(Lithiomethyl)-1-methylimidazole as a non-reactive bulk base and its novel mixed dimer with a chiral lithium amide in catalytic stereoselective deprotonationElectronic supplementary information (ESI) available: 13C NMR spectra and PM3 enthalpies. See http://www.rsc.org/suppdata/p1/b1/b104336f/

Abstract

The search for non-reactive bulk bases in replacement of lithium diisopropylamide (LDA) for improved enantioselectivity of chiral lithium amide-catalysed deprotonations led to the use of 1,2-dimethylimidazole 9 as a precursor. Deprotonation of 9 with n-BuLi in THF results in the compound 2-(lithiomethyl)-1-methylimidazole 8 as shown by NMR. This carbanionic compound is found to be less reactive than LDA in deprotonation of cyclohexene oxide 10, but having comparable basicity to that of LDA. Catalytic amounts of the chiral lithium amide 4 of (1R,2S)-N-methyl-1-phenyl-2-pyrrolidinopropanamine 5 deprotonates cyclohexene oxide 10 in the presence of compound 8 and yields (S)-cyclohex-2-enol (S)-11 in 93% ee. On the other hand, using LDA as a bulk base gives an ee of only 22%. Interestingly, stoichiometric deprotonation by 4 in the presence of 8 in THF results in (S)-11 in 96% ee. Thus, the results indicate that compound 8 is playing a more intimate role in the deprotonation than just acting as a bulk base. Therefore, the reagents involved in the reactions have been investigated by 1H, 6Li and 13C NMR using isotopically labelled compounds. The results show that lithium amide 4, which is homodimeric in THF, in the presence of 8 forms heterodimer 12 composed of one monomer of carbanionic 8 and one monomer of 4. This novel heterodimer is found to be the deprotonating reagent causing the increased enantioselectivity. It is concluded that lithium amide 4 is not basic enough to deprotonate 9, but that 8 is a strong enough base to deprotonate diamine 5. This contrasts with the behaviour of 1-methylimidazole 1 which was found to be deprotonated by 4 to yield the mixed dimer 3. Computational investigations using PM3 and B3LYP/6-31+G(d) show possible structures of the heterodimer 12 and homodimer 14 of 8, and the role of THF and 9 in the solvation of the dimers. Favoured complexes in the equilibria between homo- and heterocomplexes are reported. It is concluded that 9 will completely replace THF in the solvation of the dimers even at low concentrations of 9.