Zinc‐Mediated Formation of Trifluoromethyl Ethers from Alcohols and Hypervalent Iodine Trifluoromethylation Reagents

Abstract

A (fluor)ry of activity: The transfer of an intact trifluoromethyl group from a hypervalent iodine reagent to an aliphatic alcohol occurs smoothly upon activation by zinc bis(triflimide). This constitutes a straightforward method for the preparation of trifluoromethoxy alkyl derivatives, compounds otherwise difficult to access.

Benziodoxole-based hypervalent iodine reagents for atom-transfer reactions

“…The trifluoromethylation of 2,4,6-trimethylphenol did not only afford the expected product 64, but also the dearomatized products 65 and 66 along with other minor side products (eqn 13). 40 Unfortunately, it was not possible to optimize the 25 selectivity of the reaction. Two type of mechanisms have been proposed to explain this result.…”

“…Methyne groups were oxidized to the corresponding alcohols, whereas methylenes gave the fully oxidized carbonyls. Another 40 example of -hydroxylation of a ketone using IBX (13) was reported by Nagasawa and co-workers in the total synthesis of saxitoxin (eqn 5). 24c In this case, the reaction was discovered serendipitously when attempting the oxidation of alcohol 35.…”

“…In fact, one may argue that the lower reactivity of benziodoxole-based reagents is an obstacle for their use as oxidative functionalization reagents. In the case of highly unstable 40 structures or for the development of catalytic methods, less reactive reagents are desirable, however. Despite promising preliminary results mostly for heteroatom transfer, the number of benziodoxole-based reagents used in functionalization reactions other than simple oxidations constitutes only a 45 fraction of the reported structures and most of them are based on the  3 iodine benziodoxolone structure (Figure 1).…”

“…Karade and coworkers studied the tosyloxylation of ketones with reagent 3 in details (eqn 1). 17 Good yields were obtained for aromatic 40 and aliphatic ketones, as well as for ketoesters. Several other examples of tosyloxylation reactions using  3 or  5 -benziodoxole-based compounds were reported, but in these cases the active reagent was formed in situ.…”

“…31 A radical-like behaviour was observed at high temperature, allowing the cyanation of dimethyl aniline derivatives. 40 In fact, the rare and limited examples of cyano or aryl transfer using benziodoxole-derived reagents stand in contrast with the impressive results obtained with non-cyclic iodonium salts. 6 However, this situation is completely different when we consider CF3-transfer reactions or direct alkynylations of 45 heterocycles: for both reactions, the use of benziodoxolederived reagents was essential for success.…”