Selective Radical Fluorination of Tertiary Alkyl Halides at Room Temperature

Abstract

Direct fluorination of tertiary alkyl bromides and iodides with Selectfluor is described. The halogen‐exchange fluorination proceeds efficiently in acetonitrile at room temperature under metal‐free conditions and exhibits a wide range of functional group compatibility. Furthermore, the reactions are highly selective in that alkyl chlorides and primary and secondary alkyl bromides remain intact. A radical mechanism is proposed for this selective fluorination.

Tuning radical reactivity for selective radical/radical cross-coupling

“…The methods of generating radical from RAH bond are still limited under mild condition. Fortunately, generating radical by oxidation-induced from RAH bond, which have been widely explored during these past years, is a fascinating and unconventional approach with high atom-and step-economy [37][38][39][40][41]. Combined with the strategy of oxidation induction, great chances still remain in radical/radical cross-couplings and further exciting developments are expected.…”

Development of Monofluoroalkenes as Molecular Platform for Diversity-Oriented Syntheses of Tertiary Aliphatic Fluorides via Nickel/Manganese-Dual Catalysis

“…6,7 Accordingly, the synthetic community has shown interest in developing new strategies to access fluorinated molecules. Compared with primary and secondary alkyl fluorides, the construction of tertiary aliphatic fluorides largely relies on C-F bond formation by fluorinating tertiary carbon cations [8][9][10][11][12][13][14] (nucleophilic fluorination) or radicals [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] (electrophilic fluorination) (path a, Scheme 1). Meanwhile the elimination, solvolysis and rearrangement of in situ generated carbocation intermediates undoubtedly hampered their synthetic utility, the radical fluorination of C-H bond [15][16][17][18] or functionalized tertiary alkanes [19][20][21][22][23][24][25][26][27][28][29][30][31][32]…”

“…Compared with primary and secondary alkyl fluorides, the construction of tertiary aliphatic fluorides largely relies on C-F bond formation by fluorinating tertiary carbon cations [8][9][10][11][12][13][14] (nucleophilic fluorination) or radicals [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] (electrophilic fluorination) (path a, Scheme 1). Meanwhile the elimination, solvolysis and rearrangement of in situ generated carbocation intermediates undoubtedly hampered their synthetic utility, the radical fluorination of C-H bond [15][16][17][18] or functionalized tertiary alkanes [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] offered an alternative solution to the construction of fluorine-containing quaternary carbon center. However, the poor regiocontrol for multiple tertiary C-H centers in substrate of radical fluorinat...…”

“…Fortunately, a malonate bearing monofluoroalkene that containing an active hydrogen atom was hydroalkylated smoothly with a moderate yield (59%, 15). It should be noted that both electron-withdrawing groups, such as CF 3 (18,21), CO 2 Me (19), CN (20), and electron-donating groups, including Me ( 22), i-Pr (23), OMe (24), Ph (17), were all well tolerated under the standard conditions with acceptable yields. The electron neutral alkene (26) was conducted to examine in this reaction conditions, and obtain target product with 63% yield.…”

A third generation of radical fluorinating agents based on N-fluoro-N-arylsulfonamides

“…Following the work of Li on the Ag(I)-catalyzed fluorodecarboxylation with Selectfluor ® 19 , 20 , this reagent became the most common reagent for radical fluorination processes 11 . Using this reagent, the decarboxylative fluorination 21 – 24 has been thoroughly investigated and very recently the fluorination of tertiary alkyl halides was reported 25 . Interestingly, the fluorinative deboronation of alkylpinacolboranes and alkylboronic acids catalyzed by Ag(I) with Selectfluor ® was reported by Li (Fig.…”