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
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Abstract
Rational design of efficient chiral lithium amides for enantioselective deprotonations demands understanding of the origin of the selectivity. The mechanism of deprotonation of cyclohexene oxide 1 by lithium (1R,2S)-N-methyl-1-phenyl-2-pyrrolidinylpropanamide 3, which yields (S
)-cyclohex-2-en-1-ol (S
)-5 in 93% enantiomeric excess in
), has been investigated. Kinetics have been used to show that the reaction is first order with respect to the reagents 1 and 3, respectively. NMR investigations of a 6Li and 15N labelled isotopologue of 3 have previously shown that 3 is mainly
a dimer of the lithium amide monomer in THF in the initial state. On the basis of these results it is concluded that the rate-limiting activated complexes for the