Site-Selective Radical Trifluoromethylaminoxylation of Olefins for the Modular Synthesis of Diverse β-Trifluoromethyl Trisubstituted Hydroxylamines and Beyond

Abstract

A highly site-selective trifluoromethylaminoxylation of activated and unactivated olefins was reported under metal-free conditions. The method provides direct access to diverse β-trifluoromethyl trisubstituted hydroxylamines, tertiary alcohols, isoxazolines, isoxazolidines, and amino alcohols. The SET process between hydroxylamine and the hypervalent iodine−CF 3 reagent is proposed to produce two free radicals for the regioand diastereoselective addition to alkenes. The synthetic potential of the protocol was established via the late-stage functionalization of the products and a series of postreaction modifications.

Free Radicals in the Queue: Selective Successive Addition of Azide and N-Oxyl Radicals to Alkenes

“…It undergoes addition to an alkene to form the most stable of the two possible C-centered radicals, and this step determines the regioselectivity of the process. , The resulting C-centered radical is usually intercepted by a second R• radical − or by a stable reagent, the concentration of which should be high enough to exclude side processes. ,− Examples of such reagents include persistent radical TEMPO, O 2 , I 2 , unsaturated organic radical acceptors, or oxidants transforming radicals into carbocations for the following nucleophile addition . Difunctionalization reactions involving more than one radical that can attack a CC bond are relatively rare. − In this work, we propose a system in which two different reactive radicals (capable of attacking CC bonds) are generated: azide and N- oxyl. Each of the two radicals is capable of being added to CC bonds (Scheme b).…”

“…Similar difunctionalization processes or addition with the introduction of another functional group was reported for N- oxyl radicals. N- Oxyl radicals can both initiate the radical difunctionalization process by adding to alkene ,,, and terminate the reaction by trapping the carbon-centered radical. ,,,,,,, Despite the variety of processes that can occur in the reaction among a CC bond, N 3 •, and N -oxyl radicals, we managed to find the conditions under which the selective successive addition of an azide radical and then an N- oxyl radical occurs (Scheme b).…”

I2–DMSO mediated multicomponent convergent synthesis of imidazo[2,1-a]isoquinoline derivatives via a triple in situ cross-trapping strategy

“…4 The second type relies on parallel self-sorting reaction sequences in which two or more independent parallel tandem sequences are assembled in a single reaction, followed by cross-capture between their resulting intermediates to yield the target product (Scheme 1b). 5 However, in these reactions, the cross-capture of intermediates only occurs once or twice in one reaction procedure. Because of the mismatching of the activities of reactive intermediates, multiple cross-capture of active intermediates in situ is rarely reported.…”