A novel mixed dimer of a norephedrine-derived chiral lithium amide and 2-lithium-1-methylimidazole, and catalytic enantioselective deprotonation of cyclohexene oxide.
Improved stereoselectivity has been obtained by using 2-lithium-1-methylimidazole, 2, as a replacement for lithium diisopropylamide (LDA) as a bulk base in catalytic deprotonations. The chiral lithium amide 6 of (1R,2S)-N-methyl-1-phenyl-2-pyrrolidinylpropanamine, 5, has been found to deprotonate cyclohexene oxide 3 in the presence of compound 2 to yield (S)-cyclohex-2-en-1-ol, 4, in 96% ee. Compound 2 is a carbenoid species conveniently generated from nBuLi and 1-methylimidazole, 1. The base 2 has also been found to play a more intimate role in the deprotonation. Investigations by 1H, 6Li and 13C NMR of the 6Li/15N isotopologue 8 of 6 have shown that 6 is homodimeric in THF and that, in the presence of 2, it forms a novel heterodimer 10. This heterodimer is found to be the dominant reagent in the initial state, rather than the homodimer of 6. Computational investigations with PM3 and B3LYP/6-311 + G(d,p) have shown possible structures of the heterodimers, as well as the role of THF and I in the solvation of the dimers. The results are in line with the NMR results. Favoured complexes in the equilibria between homo- and heterocomplexes are also reported.
Amedjkouh
M
M
Organic Chemistry, Department of Chemistry, Göteborg University, Sweden.
Pettersen
D
D
Nilsson Lill
S O
SO
Davidsson
O
O
Ahlberg
P
P
D000316:Adrenergic alpha-Agonists / Q000737:chemistry; D002384:Catalysis; D003510:Cyclohexanes / Q000737:chemistry; D053138:Cyclohexenes; D019281:Dimerization; D007093:Imidazoles / Q000138:chemical synthesis*; D008094:Lithium / Q000737:chemistry*; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000138:chemical synthesis*; D010665:Phenylpropanolamine / Q000031:analogs & derivatives* / Q000737:chemistry; D013237:Stereoisomerism
D000316:Adrenergic alpha-Agonists; D003510:Cyclohexanes; D053138:Cyclohexenes; D007093:Imidazoles; D009942:Organometallic Compounds; C007193:cyclohexene oxide; D010665:Phenylpropanolamine; D008094:Lithium; C018100:1-methylimidazole