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

Abstract

Regioselective vicinal diamination of carbon–carbon double bonds with two different amines is a synthetic challenge under transition metal-free conditions, especially for the synthesis of trifluoromethylated amines. However, the synthesis of ethylene diamines and fluorinated amine compounds is demanded, especially in the pharmaceutical sector. Herein, we demonstrate that the controllable double nucleophilic functionalization of an activated alkene synthon, originated from a trifluoropropenyliodonium salt with two distinct nucleophiles, enables the selective synthesis of trifluoromethylated ethylene amines and diamines on broad scale with high efficiency under mild reaction conditions. Considering the chemical nature of the reactants, our synthetic approach brings forth an efficient methodology and provides versatile access to highly fluorinated amines.

5‐(Trifluorovinyl)dibenzothiophenium Triflate: Introducing the 1,1,2‐Trifluoroethylene Tether in Drug‐Like Structures

“…19 F NMR (282 MHz, CDCl 3 ) δ = À 72. 35 (ddd,J = 142.2,13.6,3.2 Hz),À 74.95 (ddd,J = 142.1,16.6,7.1 Hz), À 173.68 (dm, J = 45.7 Hz) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ = 134.1 (d, J = 21.7 Hz), 129.…”

“…Motivated by this ubiquity, we envisaged that the development of routes to (poly)fluorinated isosteres of this 1,2tether might be highly enabling. [7] Trifluorovinyl sulfonium salts should actually be versatile reagents for this task. [8] Addition of nucleophiles to the activated double bond of these species is expected to deliver functionalized trifluoroethyl sulfonium salts, which are known to engage in single electron transfer induced fragmentation of the S … C(H)F bond to generate fluoroalkyl radicals.…”

Stereoselective Direct N‐Trifluoropropenylation of Heterocycles with a Hypervalent Iodonium Reagent

“…In our laboratory, we recently designed and synthesized a bench stable trifluoroisopropenyl iodonium salt ( 1 ) and studied its reactivity toward nitrogen nucleophiles. Primary amines provided trifluoromethylaziridines, [14] while the utilization of secondary amines ensured the synthesis of trifluoroalkyl amines and diamines through aziridinium intermediate [15] . To complete the spectrum of applicable nitrogen nucleophiles, we studied the reaction of nitrogen heterocycles with the trifluoropropenyl‐iodonium salt to discover new synthetic possibilities and develop a stereoselective, versatile, and efficient methodology to the access of N ‐trifluoropropenyl heterocyclic species through a one‐step direct functionalization (Figure 2).…”

The advent of electrophilic hydroxylamine-derived reagents for the direct preparation of unprotected amines

“…Recent work by other groups presents additional examples for the construction of heterodiamines via an aziridinium intermediate. 83–85…”