Cobalt-Catalyzed Trifluoromethoxylation of Epoxides

Abstract

A catalytic ring-opening reaction of epoxides by nucleophilic trifluoromethoxylation of trifluoromethyl arylsulfonate has been developed based on the use of a cobalt catalyst. This reaction provides an efficient, simple route for directly construction of a wide range of vicinal trifluoromethoxyhydrins under mild conditions. In addition, this method can convert terminal epoxides into target products with good chemo-and regioselectivity.

1,2‐Bis(trifluoromethylthiolation) of Aromatic Epoxides with AgSCF3

“…The bis(trifluoromethylthiolated) product 2a was produced in high yield (Scheme 3, top), which indicated that this 1,2-bis(trifluoromethylthiolation) of epoxides probably proceeded through tandem ring-opening and deoxytrifluoromethylthiolation processes. On the basis of the above result and previous reports, [9,11,12,22] a reasonable mechanism is proposed (Scheme 3, bottom). First, the activation of AgSCF 3 generates -SCF 3 , which attacks the epoxide 1 to deliver alkoxide intermediate A.…”

Quaternary Ammonium Trifluoromethoxide Salts as Stable Sources of Nucleophilic OCF3

“…The trifluoromethoxide group has become an emerging feature in pharmaceuticals, agrochemicals, and materials. − In pharmaceuticals, trifluoromethyl ethers often exhibit improved drug properties including increased lipophilicity and metabolic stability, and can adopt unique conformations when compared with aliphatic ethers . The inclusion of a trifluoromethyl ether can also increase the potency of a drug lead .…”

Advances in the Development of Trifluoromethoxylation Reagents

“…The reaction was scalable and tolerated a wide range of functional groups. Cobalt-catalyzed trifluoromethoxylation of epoxides 68 was achieved by activation of TFMS 57 (Scheme 40) with 2,4-dinitrophenates [134]. The use of n-Bu 4 N + DNP − instead of fluorides to activate TFMS 57 enhanced nucleophilicity and stability of trifluoromethoxy anion as well as avoided formation of fluorinated byproducts.…”