Kinetic and computational studies of the composition and structure of activated complexes in the asymmetric deprotonation of cyclohexene oxide by a norephedrine-derived chiral lithium amide

摘要

Rational design of efficient chiral lithium amides for enantioselective deprotonations demands understanding of thenorigin of the selectivity. The mechanism of deprotonation of cyclohexene oxide 1 by lithium (1R,2S)-N-methyl-1-nphenyl-2-pyrrolidinylpropanamide 3, which yields (S)-cyclohex-2-en-1-ol (S)-5 in 93% enantiomeric excess inntetrahydrofuran (THF), has been investigated. Kinetics have been used to show that the reaction is first order withnrespect to the reagents 1 and 3, respectively. NMR investigations of a 6Li and 15N labelled isotopologue of 3 havenpreviously shown that 3 is mainly a dimer of the lithium amide monomer in THF in the initial state. On the basis ofnthese results it is concluded that the rate-limiting activated complexes for the epoxide deprotonation are composed ofntwo molecules of monomer of lithium amide 3 and one molecule of epoxide. Structures and energies of unsolvatednand specific THF-solvated reagents and activated complexes have been calculated using PM3 and B3LYP/6-31+G(d).nThe results are currently being explored for the rational design of chiral lithium amides with improvednstereoselectivities.