Visible-Light-Enabled Ortho-Selective Aminopyridylation of Alkenes with N-Aminopyridinium Ylides

Abstract

By utilizing an underexplored reactivity mode of N-aminopyridinium ylides, we developed the visible-light-induced ortho-selective aminopyridylation of alkenes via radical-mediated 1,3-dipolar cycloaddition. The photocatalyzed single-electron oxidation of N-aminopyridinium ylides generates the corresponding radical cations that enable previously inaccessible 1,3-cycloaddition with a broader range of alkene substrates. The resulting cycloaddition adducts rapidly undergo subsequent homolytic cleavage of the N–N bond, conferring a substantial thermodynamic driving force to yield various β-aminoethylpyridines. Remarkably, amino and pyridyl groups can be installed into both activated and unactivated alkenes with modular control of ortho-selectivity and 1,2-syn-diastereoselectivity under metal-free and mild conditions. Combined experimental and computational studies are conducted to clarify the detailed reaction mechanism and the origins of site selectivity and diastereoselectivity.

Visible-Light-Induced Sulfur-Alkenylation of Alkenes

“…During the preparation of this manuscript, the Hong group reported the photocatalytic aminopyridylation of alkenes via radicalmediated 1,3-dipolar cycloaddition and demonstrated that Naminopyridinium ylides would take the role of a 1,3-dipolar radical cation. 19 Our investigation started from the sulfur-alkenylation of activated alkenes that were irradiated with blue LEDs by investigating the reaction of α-phenacyl dithioacetal 1a with styrene 2a to find the optimal conditions, as shown in Table 1.…”

Recent advances in difunctionalization of alkenes using pyridinium salts as radical precursors

“…Inspired by the property of N-aminopyridinium ylides that they are capable of undergoing thermally induced 1,3-dipolar cycloadditions with alkynes, 46 Hong and co-workers reported C2-regioselective aminopyridylation of N-aminopyridinium ylides with alkenes via radical-mediated 1,3-dipolar cycloaddition, which led to excellent C2-regioselectivity (Scheme 31). 47 The reaction exhibited good substrate scope of alkenes, both activated (38a-38d) and unactivated alkenes (38e, 38g) afforded products in moderate to good yield. Styrenes, previously incompatible in pyridylation, 37 showed good reactivity in this transformation (38a-38b, 38f).…”

Construction of C-N Bond via Visible-Light-Mediated Difunctionalization of Alkenes

“…Wu et al in 2019 depicted (Figure 23) a visible-light-mediated Cu-catalyzed difunctionalization of alkene (37) to give azidation product (38) [27]. Here the azidobenziodoxole acts as an azidating agent in the presence of acetonitrile and [Cu(dap) 2 ]PF 6 complex as the photocatalyst.…”

“…Moon et al in 2020 demonstrated an atom-economical visible-light-mediated synthesis of aminopyridylationproduct (56) in the presence of alkenes (55) and N-aminopyridinium ylides (Figure 33) [37]. This environmentally friendly method applies to a wide range of substrates with good functional group tolerance.…”