Synthesis of Bicyclic N-Heterocycles via Photoredox Cycloaddition of Imino-Alkynes and Imino-Alkenes

Abstract

Cycloaddition reactions offer great advantages regarding atom and step economy for the construction of various carbocycles and heterocycles. While the recent development based on sensitized visible light photocatalysis allowed the synthesis of azetidines via imine-alkene [2 + 2] cycloaddition, imine-alkyne [2 + 2] cycloaddition under visible light photocatalysis has not been reported. In this regard, we report the synthesis of pyrrolizidinones based on intramolecular imine-alkyne [2 + 2] cycloaddition under visible light photocatalysis. This redox-neutral reaction involves formal imine-alkyne metathesis followed by redox-mediated annulation with concomitant rearrangement. In contrast, the use of imino-alkenes provides dihyro-1,4-oxazines via an alternative [4 + 2] cycloaddition pathway. The proposed reaction mechanisms were supported by control experiments and DFT calculations.

Regioselective Photocatalytic Dialkylation/Cyclization Sequence of 3‐Aza‐1,5‐dienes: Access to 3,4‐Dialkylated 4‐Pyrrolin‐2‐ones

“…Despite the great advances, these reactions suffer from a noble/toxic transition‐metal catalyst and/or harsh reaction conditions. Owning to its inherent green and sustainable features, visible‐light photocatalysis has proven to be a powerful and environmentally benign methodology for bond‐forming reactions and carbo‐/heterocycle syntheses over the past decade, [14] and in 2021 an intramolecular photoredox cycloaddition of elaborated imino‐alkynes was achieved by Park and co‐workers, furnishing pyrrolizidinones (Scheme 1a5) [15] . Two other mild protocols starting from nucleophilic enamines were disclosed by Wang [16] and Shibata, [17] respectively, which were both catalyzed by a transition‐metal Lewis acid.…”

“…Owning to its inherent green and sustainable features, visible-light photocatalysis has proven to be a powerful and environmentally benign methodology for bond-forming reactions and carbo-/heterocycle syntheses over the past decade, [14] and in 2021 an intramolecular photoredox cycloaddition of elaborated imino-alkynes was achieved by Park and co-workers, furnishing pyrrolizidinones (Scheme 1a5). [15] Two other mild protocols starting from nucleophilic enamines were disclosed by Wang [16] and Shibata, [17] respectively, which were both catalyzed by a transition-metal Lewis acid. A mild and sustainable synthesis of functionalized 1,3-dihydropyrrol-2-ones from readily available acyclic materials is rather appealing and rare, therefore the development of such protocols is still challenging and highly desirable.…”

New Strategies for the Synthesis of 1- and 2-Azetines and Their Applications as Value-Added Building Blocks

“…96 In contrast to the formation of a reactive cyclic intermediate such as 111 (Fig. 7B) from a 1-azetine, Müller and co-workers diversified an acyclic nitrile ylide intermediate (114) that originated from 1-azetine 113 (Fig. 7C) to form a variety of products (115-117).…”

“…100 Irradiation of 1-azetines (113) in benzene with UV light resulted in the reversible [3+1]cycloelimination of isocyanide to afford nitrile ylides 114. The nitrile ylides (114) were trapped by alcohols, dimethyl acetylenedicarboxylate, or dimethyl maleate or fumarate to provide benzimidic ester (115), 2H-pyrrole (116), or 1-pyrroline (117) products respectively. The use of acrylic esters as the dipolarophile resulted in a mixture of regioisomers.…”

“…8J). 114 Based on computational studies, it is suggested that the iminoalkyne 163 undergoes an intramolecular [2+2]-cycloaddition to 165, which then undergoes ring-opening and a second oxidation to rearrange to 166.…”