Efforts towards a Noyori reduction of a 3-fluorpiperidin-4-one with dynamic kinetic resolution. (2nd March 2021)

• Record Type: Journal Article
• Authors: LePaih, Jacques; Goff, Dane A.; Singh, Rajinder; Shaw, Simon J.
• Is Part Of: Tetrahedron letters. Volume 66(2021)
• Publication Date: 2021-03-02
• Subjects: Noyori dynamic kinetic resolution -- 3-Fluoropiperidin-4-ol -- Diastereoselective -- Enantioselective -- Building block; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2020.152764
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: Noyori Reduction of 1-Boc-3-fluoropiperidin-4-one carried out under dynamic kinetic resolution (DKR) conditions. Catalyst system is selecting between a fluorine and hydrogen atom on the piperidine ring. Reductions proceed in up to 92% de and 91% ee and to 88% de and 90% ee on scale. Crystallisation allows crude DKR product to be obtained as a pure single enantiomer. Reduction carried out on a 16 g scale. Abstract: A Noyori reduction of racemic 1-Boc-3-fluoropiperidin-4-one has been achieved under dynamic kinetic resolution conditions that results in a single cis enantiomer being obtained with both diastereo- and enantioselectivity > 90%. This medicinal chemistry building block can be generated on multi-gram scale using the developed conditions to a single enantiomer in a 60% yield after employing a crystallisation procedure.