Hydrolase-mediated resolution of the hemiacetal in 2-chromanols: The impact of remote substitution. Issue 4 (15th April 2017)

• Record Type: Journal Article
• Authors: Gavin, Declan P.; Foley, Aoife; Moody, Thomas S.; Rao Khandavilli, U.B.; Lawrence, Simon E.; O'Neill, Pat; Maguire, Anita R.
• Is Part Of: Tetrahedron, asymmetry. Volume 28:Issue 4(2017)
• Page Start: 577
• Page End: 585
• Publication Date: 2017-04-15
• Subjects: Asymmetry (Chemistry) -- Periodicals; 547.005
• DOI: 10.1016/j.tetasy.2017.04.001
• Languages: English
• ISSNs: 0957-4166

Abstract

Graphical abstract: Abstract: Hydrolase-catalysed dynamic kinetic resolutions of chroman-2-ol and 3-methyl chroman-2-ol can be effected with up to 88% conversion and 92% ee through the use of organic solvents. Extension to the resolution of the tolterodine precursor1 proved more challenging. The presence of the remote phenyl substituent had a significant impact on the resolution and it was not possible to achieve high enantioselectivity together with efficient conversion from the focussed panel of enzymes screened. Abstract : ( R )-Chroman-2-yl acetate: C11 H12 O3 94% ee [ α ]D 20 = +64.5 ( c 0.2, CHCl3 ) Source of chirality: biocatalytic enantioselective acetylation Absolute configuration: ( R ) Abstract : (2 R, 4 R )-6-Methyl-4-phenylchroman-2-yl acetate: C18 H18 O3 50% ee [ α ]D 20 = −53 ( c 0.2, CHCl3 ) Source of chirality: biocatalytic enantioselective acetylation Absolute configuration: (2 R, 4 R )