title: Optimisation of a lithium magnesiate for use in the non-cryogenic asymmetric deprotonation of prochiral ketones.
abstract: A study has been conducted to determine whether lithium magnesiates are feasible candidates for the enantioselective deprotonation of 4-alkylcyclohexanones. The commercially available chiral amine (+)-bis[(R)-1-phenylethyl]amine (2-H) was utilised to induce enantioselection. When transformed to its lithium salt and combined with (n)Bu2Mg, improved enantioselective deprotonation of 4-tert-butylcyclohexanone (with respect to the monometallic lithium amide) at 20 °C was observed. In an attempt to optimise the reaction further, different additives were added to the lithium amide. The best performing deprotonations at 0 °C were those in which (Me3SiCH2)2Mg (er pro-S 74 : 26) and (Me3SiCH2)2Mn (er pro-S 72 : 28) were added, hence the lithium magnesiate "LiMg(2)(CH2SiMe3)2" was used in the remainder of the study. The optimum solvent for the reaction was found to be THF. NMR spectroscopic studies of a D8-THF solution of "LiMg(2)(CH2SiMe3)2" appear to show that this mono-amide bis-alkyl species is in equilibrium with a bis-amide mono-alkyl compound (and a tris-alkyl lithium magnesiate). When a genuine bis-amide lithium magnesiate solution is used, the deprotonation results were essentially identical to those obtained for "LiMg(2)(CH2SiMe3)2". By adding LiCl to "LiMg(2)(CH2SiMe3)2" the er at 0 °C improved to 81 : 19. At -78 °C good yields and an er of 93 : 7 were obtained. This LiCl-containing base was used to successfully deprotonate other 4-alkylcyclohexanones.
authors.affiliation: WestCHEM, University of Strathclyde, Department of Pure and Applied Chemistry, 295 Cathedral Street, Glasgow, G1 1XL, UK. charlie.ohara@strath.ac.uk.
authors.forename: Javier
authors.initials: J
authors.lastname: Francos
authors.forename: Silvia
authors.initials: S
authors.lastname: Zaragoza-Calero
authors.forename: Charles T
authors.initials: CT
authors.lastname: O'Hara