Dynamic kinetic resolution of 2-methyl-2-nitrocyclohexanol: Combining the intramolecular nitroaldol (Henry) reaction & lipase-catalysed resolution. Issue 13 (29th March 2018)

• Record Type: Journal Article
• Authors: Foley, Aoife M.; Gavin, Declan P.; Deasy, Rebecca E.; Milner, Sinéad E.; Moody, Thomas S.; Eccles, Kevin S.; Lawrence, Simon E.; Maguire, Anita R.
• Is Part Of: Tetrahedron. Volume 74:Issue 13(2018)
• Page Start: 1435
• Page End: 1443
• Publication Date: 2018-03-29
• Subjects: Biocatalysis -- Kinetic resolution -- Henry reaction -- Dynamic kinetic resolution -- Lipases; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2018.01.055
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: 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-nitrocyclohexanol2 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 for2 . Reaction engineering allowed the design of a sequential one-pot reaction system which furnished the products with excellent enantioselectivity, and good diastereoselectivity. Graphical abstract: Herein, we describe the development of a reversible intramolecular base catalysed Henry reaction coupled with the hydrolase mediated kinetic resolution with the view to selective acetylation of a single stereoisomer is described.