Use of trifluoroacetaldehyde N-tfsylhydrazone as a trifluorodiazoethane surrogate and its synthetic applications.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30655536.
- Also identified by DOI 10.1038/s41467-018-08253-z and PMC identifier 6336877.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Trifluorodiazoethane (CF<sub>3</sub>CHN<sub>2</sub>), a highly reactive fluoroalkylating reagent, offers a useful means to introduce trifluoromethyl groups into organic molecules. At present, CF<sub>3</sub>CHN<sub>2</sub> can only be generated by oxidation of trifluoroethylamine hydrochloride under acidic conditions; due to its toxic and explosive nature, its safe generation and use remains a prominent concern, hampering wider synthetic exploitation. Here we report the development of trifluoroacetaldehyde N-tfsylhydrazone (TFHZ-Tfs) as a CF<sub>3</sub>CHN<sub>2</sub> surrogate, which is capable of generating CF<sub>3</sub>CHN<sub>2</sub> in situ under basic conditions. The reaction conditions employed in this chemistry enabled a difluoroalkenylation of X-H bonds (X = N, O, S, Se), affording a wide range of heteroatom-substituted gem-difluoroalkenes, along with Doyle-Kirmse rearrangements and trifluoromethylcyclopropanation reactions, with superior outcomes to approaches using pre-formed CF<sub>3</sub>CHN<sub>2</sub>. Given the importance of generally applicable fluorination methodologies, the use of TFHZ-Tfs thus creates opportunities across organic and medicinal chemistry, by enabling the wider exploration of the reactivity of trifluorodiazoethane.