Visible-Light-Mediated α-Amino Alkylation of Azomethine Imines: An Approach to N-(β-Aminoalkyl)pyrazolidinones

Abstract

Herein, a mild and robust photocatalytic protocol for the combination of amino and pyrazolidinone functionalities through a radical α-amino alkylation of azomethine iminium ions is demonstrated. This method presents a high functional group tolerance providing direct access to a large family of N-(β-aminoalkyl)­pyrazolidinones in good to excellent yields, including the late-stage incorporation of the pyrazolidinone moiety to pharmaceutical ingredients. We propose a plausible scenario for the C–C bond-forming step which involves radical addition followed by a spin-center-shift event.

Visible-light-mediated synthesis of α,β-diamino esters via coupling of N,N-dimethylanilines and glyoxalic oxime ethers

“…21–26 Rueping and coworkers have reported a visible-light-mediated synthesis of vicinal diamines via coupling of aldimines and dimethylanilines. 19 Paixão et al have developed a visible-light-mediated protocol for the α-amino alkylation of azomethine imine 27 toward the synthesis of N -(β-aminoalkyl)pyrazolidinones (Scheme 1b).…”

Photoinduced carbamoylation reactions: unlocking new reactivities towards amide synthesis

“…Azomethine imines 25 are building blocks widely known by their reactivity as 1,3-dipoles, and are employed in the preparation of biologically relevant nitrogenated heterocycles through [3+2] and [3+3] cycloadditions. 76 However, few protocols in which azomethine imines engage in photocatalytic radical couplings have been reported, 77 including an organophotocatalytic amidation protocol using carbamoyl-DHPs as radical sources, developed by Paixão and co-workers (Scheme 15). 78 This new strategy was initially tested towards a set of azomethine imines, being amenable to electron-rich and electron-poor (hetero)aromatic scaffolds and affording the respective pirazolidinone-amides 26 in moderate to good yields, including an analog bearing the pharmaceutical ingredient etodolac 26c .…”

Visible-light-promoted generation of p-(N,N-dimethyl)benzyl equivalents and their reactions with quinols: easy access to diarylalkanes

“…Nitrogen-containing species have attracted great interest in the field of organic synthesis for their wide potential utilization as drugs, agrochemicals, and functional synthetic materials. In recent years, α-amino alkyl radicals, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] which could be conveniently generated under photoredox catalysis (Scheme 1a), [19][20][21][22][23][24] have become a valuable nitrogen-containing intermediate for the synthesis of amino acids and alkaloids. [25][26][27] α-Amino alkyl radicals come from the singleelectron reduction of imines or iminium ions that are derived from reactions of aldehydes and amines.…”