Electrochemical Synthesis of Allylic Amines from Terminal Alkenes and Secondary Amines

Abstract

Allylic amines are valuable synthetic targets en route to diverse biologically active amine products. Current allylic C− H amination strategies remain limited with respect to the viable N-substituents. Herein, we disclose a new electrochemical process to prepare aliphatic allylic amines by coupling two abundant starting materials: secondary amines and unactivated alkenes. This oxidative transformation proceeds via electrochemical generation of an electrophilic adduct between thianthrene and the alkene substrates. Treatment of these adducts with aliphatic amine nucleophiles and base provides allylic amine products in high yield. This synthetic strategy is also amenable to functionalization of feedstock gaseous alkenes at 1 atm. In the case of 1-butene, high Zselective crotylation is observed. This strategy, however, is not limited to the synthesis of simple building blocks; complex biologically active molecules are suitable as both alkene and amine coupling partners. Preliminary mechanistic studies implicate vinylthianthrenium salts as key reactive intermediates.

Quantitative Evaluation of the Hydrogen‐Donating Abilities ofAmines and Amides in Acetonitrile

“…Hydrogen atom transfer (HAT, equation 1) plays a key role in a variety of important chemical and biological processes such as the radical scavenging activity of natural and synthetic antioxidants [1][2][3] and CÀ H functionalization. [4][5][6] Amines are often used as nucleophiles in synthesis [7][8][9] and amides are widely used as solvents for a variety of purposes, and are often taken as simple models for peptide bonds in proteins and polypeptides. [10][11][12] Amines and amides have attracted great interest as the antioxidants employed in studies.…”

Allylic C–H amination cross-coupling furnishes tertiary amines by electrophilic metal catalysis

“…The addition of amines to terminal olefins provides a direct route to these important compounds that uses robust commercial building blocks (9)(10)(11)(12). Advances in tandem radical-mediated olefin functionalization-elimination processes underscore the advantages of olefin-amine coupling (13,14). Metal-mediated allylic C-H amination provides an orthogonal methodology, where greater control of reactivity, selectivity, and functional group compatibility may be achieved.…”

“…Remote carbonyl functionality, generally reactive with secondary amines and challenging to maintain in reductive or radical-based amination methods (5,(9)(10)(11)(12)(13)(14), was compatible with the oxidative conditions of AACC catalysis. Olefins containing aldehyde, ketone, ethyl ester, and gem-dimethyl ester functionalities afforded excellent yields of tertiary amine products (41 to 44).…”

General and Practical Metal-Free Aziridination and Cyclopropanation of XH2 (X = N, C) with Alkenes by Thianthrenation

“…[37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52] In 2021, Wickens and our group independently reported the functionalization of alkenes by thianthrenation to formally transform allylic C-H bond to form C-C, C-O, and C-N bonds with C-, O-, and N-based nucleophiles (Scheme 1b, bottom). 53,54 Herein, a general and practical protocol for cyclopropanation and aziridination using free XH2 (X = C and N) with alkenes by thianthrenation was developed (Scheme 1c). Notably, free amides, sulfonamides, amines, carbamates, and methylenes with acidic protons are used as the precursors.…”

“…Based on the experimental results and literature, 26,53,54 a plausible mechanism is proposed and depicted in Scheme 5. First, the dithianthrenium salt M1 was formed by intramolecular attack of sulfur on the olefinic moiety of the vinyl thianthrenium salt.…”