Biocatalytic Conversion of Cyclic Ketones Bearing α‐Quaternary Stereocenters into Lactones in an Enantioselective Radical Approach to Medium‐Sized Carbocycles. Issue 14 (5th March 2018)

• Record Type: Journal Article
• Authors: Morrill, Charlotte; Jensen, Chantel; Just‐Baringo, Xavier; Grogan, Gideon; Turner, Nicholas J.; Procter, David J.
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 14(2018)
• Page Start: 3692
• Page End: 3696
• Publication Date: 2018-03-05
• Subjects: biocatalysis -- cyclization -- lactones -- radicals -- samarium; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201800121
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Cyclic ketones bearing α‐quaternary stereocenters underwent efficient kinetic resolution using cyclohexanone monooxygenase (CHMO) from Acinetobacter calcoaceticus . Lactones possessing tetrasubstituted stereocenters were obtained with high enantioselectivity (up to >99 % ee ) and complete chemoselectivity. Preparative‐scale biotransformations were exploited in conjunction with a SmI2 ‐mediated cyclization process to access complex, enantiomerically enriched cycloheptan‐ and cycloctan‐1, 4‐diols. In a parallel approach to structurally distinct products, enantiomerically enriched ketones from the resolution with an α‐quaternary stereocenter were used in a SmI2 ‐mediated cyclization process to give cyclobutanol products (up to >99 % ee ). Abstract : Best of both worlds : Cyclic ketones with α‐quaternary centers underwent kinetic resolution with a cyclohexanone monooxygenase (CHMO) to give lactones with tetrasubstituted stereocenters with high enantioselectivity (see scheme). Subsequent SmI2 ‐mediated cyclization led to complex cycloheptan‐ and cycloctan‐1, 4‐diols. Enantiomerically enriched cyclic ketones from the resolution were converted into cyclobutanols by SmI2 ‐mediated cyclization.