Buchler Glossary

Enantioselective Fluorination

Fluorination is for instance a replacement of one hydrogen atom within a molecule by fluorine. The incorporation of fluorine often induces significant changes of chemical and biological properties, including bioactivity, metabolic stability, and pharmacokinetics, of the parent compounds. Therefore the selective construction of carbon-fluorine bonds is of great interest to medicinal chemists because the replacement of hydrogen and oxygen atoms with fluorine atom in biologically active molecules can confer molecules with improved physicochemical properties and biological activities. Cinchona alkaloids have been prominently featured from the infancy of asymmetric fluorination.

Enantioselective Fluorination

Cinchona alkaloid/Selectfluor combinations efficiently fluorinate a variety of carbonyl compounds in a highly enantioselective manner to furnish chiral α-fluorocarbonyl compounds. This combination was found to be an effective enantioselective fluorinating reagent for a wide range of substrates such as silyl enol ethers, β-keto esters, arylcyano esters, and oxindoles without any additives.

Apart from other Cinchona alkaloid compounds especially bifunctional chiral thioureas have been successfully used as organocatalysts. For example in enantioselective fluorinations of β-keto esters. The corresponding products could be obtained with good to excellent enantioselectivity in high yields by using N-fluorobisbenzenesulphonimide (NFSI) as fluorination reagent. Often the Cinchona alkaloid catalyst can be recycled easily.

You will find a lot of enantioselective fluorination reactions in our free of charge Chiral Catalyst Search Data Base.

Example from Literature

One-pot fluorination and asymmetric Michael addition promoted by recyclable fluorous organocatalysts. (Zhang et al.; RSC Adv. 2013, 3, 18267–18270.) In this case a fluorous bifunctional cinchona alkaloid-thiourea organocatalyst has been used for the synthesis of α-fluoro-β-ketoesters bearing two chiral centers.

Fluorination example

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