Visible-Light-Mediated Amination of π-Nucleophiles with N-Aminopyridinium Salts

Abstract

Under UV light irradiation N,N-(diphenylamino)pyridinium salts generate nitrenium ions.Herein, we report that in the presence of a photoredox catalyst nitrogen-centered radicals form which can then react with enol equivalents to give α-amino carbonyl compounds in excellent yields. The broad synthetic utility of this method is demonstrated by functionalization of ketones, aldehydes, esters enol equivalents, vinyl ethers and 1,3-diketones without the need for prior conversion to enol derivatives. The developed method is easily scalable, offers broad substrate scope, high chemoselectivity, and mild conditions.

Visible-Light-Mediated Amination of π-Nucleophiles with N-Aminopyridinium Salts

“…Such reactivity would pose a novel approach toward amination of carbonyl compounds allowing convenient access to α-amino ketones, aldehydes, unnatural amino acids, and so forth − compounds of significance for synthetic chemists. 29…”

“…Given our long-standing interest in photoredox catalysis, we envisioned that electrophilic N-centered radicals generated from N -aminopyridinium salts should be trapped by nucleophilic enol derivatives leading to the formation of the C–N bond (Scheme B). Such reactivity would pose a novel approach toward amination of carbonyl compounds allowing convenient access to α-amino ketones, aldehydes, unnatural amino acids, and so forth − compounds of significance for synthetic chemists …”

Diversification of Amidyl Radical Intermediates Derived from C–H Aminopyridylation

“…In addition to olefinic substrates, the electrophilic radicals generated by reductive activation of the N−N bonds in Nbenzylaminopyridiniums engage in amination reactions with nucleophilic heterocycles, such as N-Boc-indole 6 to afford 2aminated indole 7 in 47% yield (Figure 4a) and silyl enol ethers (8) to afford α-amino carbonyls 9 (Figure 4b). The amination of silyl enol ethers via N-aminopyridiniums, 12 which represents a formal aza-Rubottom reaction, tolerates both substitution of the nucleophilic partner 8 (i.e., preparation of 9a−9e) as well as variation of the benzylic substituents on the N-benzylpyridinium partner 2 (i.e., preparation of 9f and 9g). Synthesis of 9a could be performed on a 1 mmol scale with 61% isolated yield (see Supporting Information of additional details).…”

Direct alpha-Amination of Amides and Lactams Enabled by the (3+2) Vinyl Azide-Enolate Cycloaddition Manifold

“…[11][12][13][14][15] Methods using native carbonyl reactivity rely on electrophilic nitrogen sources, typically affording α-hydrazinyl, [16][17][18][19][20][21][22][23][24] hydroxyamino, [25][26][27][28] α-azido [29] or nitro [30] products, that then undergo further manipulation to afford the target -amino carbonyl species (Figure 1A). [31][32][33][34][35][36][37][38] In nucleophilic amination involving umpolung of carbonyl compounds, -oxidation or -halogenation of the carbonyl fragment allows coupling to an amine, although these methods were until recently limited to construction of tertiary amines (Figure 1B). [39][40][41][42][43][44][45][46][47][48][49][50] A consequence of umpolung-based approaches is the necessity for multiple steps to effect the necessary polarity reversal of one reaction component.…”