AI Article Synopsis
- The trifluoromethylthio group (SCF) is important in drug design due to its special electronic traits, stability, and high lipophilicity, but making its enantioselective derivatives is difficult.
- A new method using iridium as a catalyst successfully facilitates the enantioselective trifluoromethylthiolation of propargylic C(sp)-H bonds in alkynes, showing effectiveness with various substrates, including those related to natural products and drugs.
- This technique not only produces high yields and good stereoselectivity for trifluoromethyl thioethers but can also be adapted to create other valuable derivatives like difluoromethyl and chlorodifluor
Article Abstract
The trifluoromethylthio group (SCF) has gained increasing prominence in the field of drug design and development due to its unique electronic properties, remarkable stability, and high lipophilicity, but its derivatives remain challenging to access, especially in an enantioselective manner. In this Communication, we present an enantioselective iridium-catalyzed trifluoromethylthiolation of the propargylic C(sp)-H bonds of alkynes. This protocol demonstrates its efficacy across a diverse array of alkyne substrates, including B- and Si-protected terminal alkynes as well as those derived from natural products and pharmaceuticals, to give trifluoromethyl thioethers with good to excellent yield and stereoselectivity. Moreover, this protocol could be modified to access enantioenriched difluoromethyl and chlorodifluoromethyl thioethers (SCFH and SCFCl derivatives), significantly expanding the space of synthetically accessible enantioenriched fluoroorganic compounds.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487557 | PMC |
| http://dx.doi.org/10.1021/jacs.4c12093 | DOI Listing |
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