Synthesis of Enantioenriched Alkylfluorides by the Fluorination of Boronate Complexes.

Christopher Sandford,Ramesh Rasappan,Varinder K Aggarwal

doi:10.1021/jacs.5b05848

Christopher Sandford, Ramesh Rasappan + Show 1 more

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https://doi.org/10.1021/jacs.5b05848

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Abstract

The enantiospecific conversion of chiral secondary boronic esters into alkylfluorides is reported. Boronate complexes derived from boronic esters and PhLi were used as nucleophiles, with Selectfluor II as the electrophilic fluorinating agent, to afford alkylfluorides in short reaction times. The addition of styrene as a radical trap was found to enhance enantiospecificity. A broad range of alkyl boronic esters were converted into alkylfluorides with almost complete enantiospecificity by this method.

Highlights

Boronate complexes derived from boronic esters and PhLi were used as nucleophiles, with Selectfluor II as the electrophilic fluorinating agent, to afford alkylfluorides in short reaction times
The incorporation of fluorine into an organic compound can result in improved metabolic stability and bioavailability and enhance the binding efficacy when compared to the nonfluorinated analogue.[2]
Late-stage fluorination techniques are of particular importance because they can be used to introduce 18F into molecules for positron emission tomography (PET).[4]

Summary

Introduction

Boronate complexes derived from boronic esters and PhLi were used as nucleophiles, with Selectfluor II as the electrophilic fluorinating agent, to afford alkylfluorides in short reaction times. F0.25 mmol of 4a and 0.95 equiv of PhLi. Conditions: Ate complex formation at 0 °C (30 min) in 2.5 mL of THF, fluorination at −10 °C (2 h) in 5.0 mL of MeCN (total), with 1.3 equiv of Selectfluor and 3 Å molecular sieves (powder, 100 mg).

Results

Conclusion