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Dynamic kinetic resolution of 2-methyl-2-nitrocyclohexanol: Combining the intramolecular nitroaldol (Henry) reaction & lipase catalysed resolution
Foley, Aoife M.
Gavin, Declan P.
Deasy, Rebecca E.
Milner, Sinéad E.
Moody, Thomas S.
Eccles, Kevin S.
Lawrence, Simon E.
Maguire, Anita R.
Efforts to combine the intramolecular nitroaldol reaction with lipase-catalysed resolution of the resulting nitroaldol adduct in a one-pot dynamic kinetic resolution (DKR) are described. Significant challenges were encountered in the combination of the two systems. trans-2-Methyl-2-nitrocyclohexyl acetate (±)-3b was isolated in excellent enantiopurity (>98% ee) via a sequential DKR sequence where the lipase-mediated resolution and base-mediated interconversion of 2-methyl-2-nitrocyclohexanol 2 were effected alternately, demonstrating the feasibility of this approach initially. Further work showed, for the first time, evidence that a DKR-type system is possible for 2. Reaction engineering allowed the design of a sequential one-pot reaction system which furnished the products with excellent enantioselectivity, and good diastereoselectivity.
Biocatalysis , Kinetic resolution , Henry reaction , Dynamic kinetic resolution , Lipases
Foley, A. M., Gavin, D. P.; Deasy, R. E., Milner, S. E., Moody, T. S., Eccles, K. S., Lawrence, S. E. and Maguire, A. R. (2018) 'Dynamic kinetic resolution of 2-methyl-2-nitrocyclohexanol: Combining the intramolecular nitroaldol (Henry) reaction & lipase catalysed resolution', Tetrahedron, 74(13), pp. 1435-1443. doi:10.1016/j.tet.2018.01.055