From Olefination to Alkylation:
In-Situ Halogenation
of Julia–Kocienski Intermediates Leading to Formal Nucleophilic
Iodo- and Bromodifluoromethylation of Carbonyl Compounds
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Abstract
Iodo- and bromodifluoromethylated compounds are important
synthetic
intermediates and halogen-bond acceptors. However, direct introduction
of −CF<sub>2</sub>I and −CF<sub>2</sub>Br groups through
nucleophilic addition is particularly challenging because of the high
tendency of decomposition of CF<sub>2</sub>Br<sup>–</sup> and
CF<sub>2</sub>I<sup>–</sup> to difluorocarbene. In this work,
we have developed a formal nucleophilic iodo- and bromodifluoromethylation
for carbonyl compounds. The key strategy of the method is the halogenation
of in situ-generated sulfinate intermediates from the Julia–Kocienski
reaction to change the reaction pathway from the traditional olefination
to alkylation. Interesting halogen−π interactions between
the halocarbon and aromatic donors were observed in the crystal structures
of the products. The method could also be extended to the introduction
of other fluorinated groups, such as −CFClBr, −CFClI,
−CFBr<sub>2</sub>, and −CFMeI, which opens up new avenues
for the synthesis of a wide range of useful fluorinated products
