Highly Diastereoselective Synthesis of γ-Lactams Enabled by Photoinduced Deaminative [3 + 2] Annulation Reaction

Abstract

The photoinitiated deaminative [3 + 2] annulation reaction of N-aminopyridinium salts with alkenes for the synthesis of functionalized γ-lactams is described. This transformation shows good functional group tolerance as well as excellent diastereoselectivity. Preliminary studies suggest that the employed N-aminopyridinium salts generate the key amidyl radical intermediates through N–N bond cleavage via a photoinduced single-electron transfer (SET) process. The amidyl radical species would add to the double bond of alkenes, followed by a radical-mediated annulation process, to afford the desired γ-lactams.

N-Amino pyridinium salts in organic synthesis

“…In 2022, Yang and Xia et al reported a deaminative [3 + 2] annulation method for the synthesis of γ-lactams (Scheme 23) that was initiated by reductive cleavage of the N–N bond of 69 . 61 Following the general mechanism described in Scheme 11, the N -centered radical generated from the triphenyl N -aminopyridinium derivative 69 adds to styrene 49 to generate the carbon-centered radical, which undergoes further intramolecular 5- exo-trig cyclization followed by oxidation to the benzylic carbocation. Product 70 is delivered by trapping the incipient carbocation with solvent.…”

Recent advances of aminoazanium salts as amination reagents in organic synthesis

“…Recently, Xia et al realized the synthesis of functionalized γ-lactams through the photoinitiated [3 + 2] annulation of N -aminopyridinium salts with styrenes. 45 The N -aminopyridinium salts 62 bearing the CC bond were synthesized from cinnamamide. The salts could yield the amidyl radical 28A in the presence of the photocatalyst.…”

Copper-Catalyzed Sulfonylation/Cyclization of Pent-4-ynamides toward Sulfonyl-Functionalized Pyrrol-2-ones

“…Unsurprisingly, it has long been a research interest of the chemical community for the development of efficient methods for the preparation of γ-lactams with various substitution patterns . Much progress has been made recently in this line during the past decade, − with particular attention paid to intramolecular olefin amidation of unsaturated amides by transition-metal (TM) catalysis or amidyl radical cyclization (Scheme , eq 1). Despite these advances, however, the development of new methodologies for rendering diversely functionalized γ-lactam derivatives constructed conveniently from readily available precursors is still highly desirable.…”