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A Novel Mixed Dimer of a Norephedrine‐Derived Chiral Lithium Amide and 2‐Lithium‐1‐methylimidazole, and Catalytic Enantioselective Deprotonation of Cyclohexene Oxide
Author(s) -
Amedjkouh Mohamed,
Pettersen Daniel,
Nilsson Lill Sten O.,
Davidsson Öjvind,
Ahlberg Per
Publication year - 2001
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20011015)7:20<4368::aid-chem4368>3.0.co;2-k
Subject(s) - lithium amide , chemistry , deprotonation , cyclohexene oxide , lithium diisopropylamide , dimer , amide , carbenoid , enantioselective synthesis , lithium (medication) , stereoselectivity , stereochemistry , catalysis , medicinal chemistry , cyclohexene , organic chemistry , medicine , ion , rhodium , endocrinology
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 (1 R ,2 S )‐ 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 n BuLi and 1‐methylimidazole, 1 . The base 2 has also been found to play a more intimate role in the deprotonation. Investigations by 1 H, 6 Li and 13 C NMR of the 6 Li/ 15 N 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 1 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.