Synthesis of α-CF₃and α-CF₂H aminesviathe aminofluorination of fluorinated alkenes

Abstract

A novel synthesis of α-CF3 and α-CF2H amines via the aminofluorination of gem-difluoroalkenes and mono-fluoroalkenes, respectively, is reported. The method employs Selectfluor as an electrophilic fluorine source and acetonitrile as a nitrogen source. Mechanistic studies revealed a single-electron oxidation/fluorine-abstraction/Ritter-type amination pathway. The protocol allowed the synthesis of a broad range of fluorinated amines including those bearing quaternary carbon centers with good efficiency and functional group tolerance.

Recent Applications of Ritter Reactions in Organic Syntheses

“…In 2018, a new synthesis of α-CF 3 amides 165 was synthesized by the Ritter reaction of acetonitrile 47 and gem-difluoroalkenes 164 in the presence of selectfluor as catalyst and Tf 2 NH as a base (Scheme 71). [71] In 2018, the synthesis of α-CF 2 H amines 167 was reported by the non-classical Ritter reaction of acetonitrile 47 and mono-flouroalkenes 166 via the fluorine-abstraction/singleelectron oxidation (Scheme 72). [71] Gem-difluoroalkene 166 was oxidized in the presence of Selectfluor through the single electron oxidation to generate an alkene radical cation 168, which was created a benzylic cation 169 through the cage regioselective fluorine atom abstraction by reduced Selectfluor.…”

“…[71] In 2018, the synthesis of α-CF 2 H amines 167 was reported by the non-classical Ritter reaction of acetonitrile 47 and mono-flouroalkenes 166 via the fluorine-abstraction/singleelectron oxidation (Scheme 72). [71] Gem-difluoroalkene 166 was oxidized in the presence of Selectfluor through the single electron oxidation to generate an alkene radical cation 168, which was created a benzylic cation 169 through the cage regioselective fluorine atom abstraction by reduced Selectfluor. In the last step, benzylic cation 169 was reacted to acetonitrile and H 2 O through the Ritter-type amination to give the target product 167 (Scheme 73).…”

“…In 2018, a new synthesis of α ‐CF 3 amides 165 was synthesized by the Ritter reaction of acetonitrile 47 and gem‐difluoroalkenes 164 in the presence of selectfluor as catalyst and Tf 2 NH as a base (Scheme 71). [71] …”

Base‐Mediated N‐Arylation for the Synthesis of 9H‐Pyrrolo[1,2‐a]indol‐9‐ones and 10H‐Indolo[1,2‐a]indol‐10‐ones

“…[3] Therefore, it offers great opportunities to develop alternative pathways constructing CÀ N bonds. [4,5] Since the first report of transition-metal-free couple reaction, [6] great success and significance in this field are highlighted increasingly in organic synthesis. [7 -13] However, reports concerning transition-metal-free CÀ N bond formation are limited.…”

Vicinal difunctionalization of carbon–carbon double bond for the platform synthesis of trifluoroalkyl amines

“…1e) [41][42][43][44] . In this respect, the syntheses of homo-and heterofunctionalized, α-trifluoromethyl vicinal diamines [45][46][47][48][49][50][51][52] and other substituted trifluoropropylamines [52][53][54][55] are demanding.…”