Photoinduced oxidative cyclopropanation of ene-ynamides: synthesis of 3-aza[n.1.0]bicycles via vinyl radicals

Abstract

The first photoinduced synthesis of polyfunctionalized 3-aza[n.1.0]bicycles from readily available ene-ynamides and 2,6-lutidine N-oxide using organic acridinium photocatalyst is reported. Applying a photocatalytic strategy to the reactive distonic cation vinyl...

Visible Light‐Mediated Manipulation of 1,n‐Enynes in Organic Synthesis

“…[44] In 2021, Deng and coworkers demonstrated the acridinium photocatalyzed cyclopropanation of ene-ynamides 39 with 2,6-lutidine N-oxide 40 to synthesize 3-aza[n.1.0]bicycles 41 (Scheme 14). [45] In this protocol, a wide variety of 3-azabicyclo[5.1.0]octane, 3azabicyclo[4.1.0]heptane, and 3-azabicyclo[3.1.0]hexan-2-one derivatives 41 were synthesized in good to excellent yields (61-92 % yields). In this protocol, two possible pathways were suggested for the formation of key oxypyridinium tethered vinyl radical intermediate 14 C. First (Path-A), the ene-ynamide 39 [E 1/2 = + 1.58 V vs. SCE] [45] is oxidized by the photoexcited catalyst [E 1/2 (*Mes-Acr + /Mes-Acr * ) = + 2.17 Besides, the synthesis of azetidines has gained attention over the years due to their amplified bioavailability, pharmacokinetics, and metabolic properties.…”

“…[45] In this protocol, a wide variety of 3-azabicyclo[5.1.0]octane, 3azabicyclo[4.1.0]heptane, and 3-azabicyclo[3.1.0]hexan-2-one derivatives 41 were synthesized in good to excellent yields (61-92 % yields). In this protocol, two possible pathways were suggested for the formation of key oxypyridinium tethered vinyl radical intermediate 14 C. First (Path-A), the ene-ynamide 39 [E 1/2 = + 1.58 V vs. SCE] [45] is oxidized by the photoexcited catalyst [E 1/2 (*Mes-Acr + /Mes-Acr * ) = + 2.17 Besides, the synthesis of azetidines has gained attention over the years due to their amplified bioavailability, pharmacokinetics, and metabolic properties. [46] In this framework, Bai, Yuan, Zhu, and co-workers recently published a unique approach for constructing polysubstituted azetidines 44 by reacting with N-allyl sulfonyl amides 42 with Togni's reagent 43 (Scheme 15).…”

“…In 2021, Deng and co‐workers demonstrated the acridinium photocatalyzed cyclopropanation of ene‐ynamides 39 with 2,6‐lutidine N ‐oxide 40 to synthesize 3‐aza[ n .1.0]bicycles 41 (Scheme 14). [45] In this protocol, a wide variety of 3‐azabicyclo[5.1.0]octane, 3‐azabicyclo[4.1.0]heptane, and 3‐azabicyclo[3.1.0]hexan‐2‐one derivatives 41 were synthesized in good to excellent yields (61–92 % yields). In this protocol, two possible pathways were suggested for the formation of key oxypyridinium tethered vinyl radical intermediate 14 C .…”

“…First (Path‐A), the ene‐ynamide 39 [E 1/2 =+1.58 V vs . SCE] [45] is oxidized by the photoexcited catalyst [E 1/2 (*Mes‐Acr+/Mes‐Acr⋅)=+2.17 V vs . SCE] to deliver the ynamide cation radical 14 B , which on nucleophilic addition by the 2,6‐lutidine N ‐oxide 40 , leads to the generation of the key radical intermediate 14 C .…”

Photoinduced ynamide structural reshuffling and functionalization

“…In addition, metal/oxidant/photocatalyst-induced radical addition to the α/β-carbons of ynamides leads to a mixture of E / Z isomers in the products (Fig. 1b ) 25 – 28 . Recently, professors Gandon, Sahoo and coworkers observed an intermolecular radical-triggered reactivity of alkynes vs. ynamides in yne‐tethered ynamides with sulfur radicals under traditional reaction conditions (Fig.…”