Foley, Aoife M.; Gavin, Declan P.; Deasy, Rebecca E.; Milner, Sinéad E.; Moody, Thomas S.; Eccles, Kevin S.; Lawrence, Simon E.; Maguire, Anita R.

2018

February

Tetrahedron

Dynamic kinetic resolution of 2-methyl-2-nitrocyclohexanol: Combining the intramolecular nitroaldol (Henry) reaction & lipase catalysed resolution

Validated

WOS: 8 ()

Biocatalysis Kinetic resolution Henry reaction Dynamic kinetic resolution Lipases

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.

0040-4020

https://www.sciencedirect.com/science/article/pii/S0040402018301157

10.1016/j.tet.2018.01.055