Fluorinated motifs in chemical structures, as well as their synthesis, have become of great interest in the past fifteen years due to their unique properties when added to medicinal compounds. Records show that in 1970 only around 2% of the pharmaceutical drugs contained at least one fluorine atom in their structure yet in 2014, there has been reported that at least 25% of the medicinal compounds contain fluorine, some of them making the top selling pharmaceuticals list such as Lipitor®, Prevacid® and Proxac®. To achieve tetrasubstituted α,α- chlorofluoroalcohols, in Scheme 1 a saturated aldehyde is taken in the presence of N-chlorosuccinimide (NCS) and L-proline as a catalyst in order to produce the α-Chloroaldehyde. Upon the addition of NFSI (N-Fluorodibenzenesulfonimide) and a prolinol derived catalyst, (S)-α, α-bis[3,5-bis(trifluoromethyl)phenyl]-2-pyrrolidinemethanol trimethylsilyl ether (1a), to the α-chloroaldehyde, a geminal chlorofluoro quaternary center in the α-position of the aldehyde results. After reduction to the alcohol and separation by column chromatography products are isolated in high yield and good enantioselectivity. These enantio-pure tetrasubstituted stereo centers can undergo SN2 to form new functionalized fluorinated quaternary centers that can be applied in the design and synthesis of novel medicinal compounds.

Developing an organocascade methodology to achieve α,α-chlorofluoroalcohols

251st National Meeting (2016)

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