Chemoenzymatic Asymmetric Synthesis of Pyridine‐Based α‐Fluorinated Secondary Alcohols. (7th October 2021)

• Record Type: Journal Article
• Authors: Broese, Timo; Ehlers, Peter; Langer, Peter; von Langermann, Jan
• Is Part Of: Chembiochem. Volume 22:Number 23(2021)
• Page Start: 3314
• Page End: 3318
• Publication Date: 2021-10-07
• Subjects: alcohol -- enzymes -- enantioselectivity -- fluorine -- heteroaromatic; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.202100392
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: Fluoro‐substituted and heteroaromatic compounds are valuable intermediates for a variety of applications in pharma‐ and agrochemistry and synthetic chemistry. This study investigates the chemoenzymatic preparation of chiral alcohols bearing a heteroaromatic ring with an increasing degree of fluorination in α‐position. Starting from readily available picoline derivatives prochiral α‐halogenated acyl moieties were introduced with excellent selectivity and 64–95 % yield. The formed carbonyl group was subsequently reduced to the corresponding alcohols using the alcohol dehydrogenase from Lactobacillus kefir, yielding an enantiomeric excess of 95–>99 % and up to 98 % yield. Abstract : Two for one : A straightforward chemoenzymatic synthesis pathway towards valuable chiral alcohols with α‐fluorination in close proximity to the chiral center and a pyridine ring is presented. High conversions with excellent enantioselectivities were found, showing its high synthetic potential.