Photocatalytic Cascade Radical Cyclization Approach to Bioactive Indoline-Alkaloids over Donor–Acceptor Type Conjugated Microporous Polymer

Abstract

Herein, we describe a visible-light-induced radical strategy for the 1,2-formylarylation of N-arylacrylamides via the C–H activation of 1,3-dioxolane using a carbazolic-cyano conjugated microporous polymer (CC-CMP) as a metal-free photocatalyst. This process provides an efficient and mild approach for constructing highly functionalized formyl-substituted oxindoles, which are valuable building blocks that allow rapid access to various important heterocycle-fused and spirocyclic indole alkaloids. Utilizing this strategy, bioactive alkaloids, such as (±)-desoxyeseroline, (±)-esermethole, and (±)-N-Me-coerulescine, have been concisely synthesized in up to 74% overall yield from low-cost acrylamides and 1,3-dioxolane. The overall yields of our approach are much higher than those of conventional multistep methods. Gram-scale syntheses of natural alkaloids have been demonstrated, highlighting the practical utility of this protocol. The use of CC-CMP photocatalysts, which are metal-free, flexible, stable, effective, and reusable, making this strategy appealing to advanced chemical manufacturing.

Acetal Addition to Electron-Deficient Alkenes with Hydrogen Atom Transfer as a Radical Chain Propagation Step

“…Mechanistically, a dioxolanyl moiety adds to an electrophilic acceptor. After the first radical addition step, the resulting radical may undergo single-electron transfer (SET), ,, trapping with a second radical acceptor, or atom transfer reactions, for example, HAT. ,, Among the three possible pathways, HAT is less commonly observed, specifically in a radical-chain mechanism. ,, Here, we report the visible-light-induced addition of a hydrogen atom and acetal carbon to electron-deficient alkenes via a radical chain mechanism enabled by HAT as a propagating step (Scheme e), the transformation previously demonstrated by the Tomioka group under distinct reaction conditions. , …”

Direct transfer of tri- and di-fluoroethanol units enabled by radical activation of organosilicon reagents

“…Both electron-donating OMe and electron-withdrawing CO 2 Me on the arenes were maintained after the reaction. It is worthy to note that compounds 11 are difficult to be synthesized through the nucleophilic trifluoromethylation reaction of aldehydes with TMSCF 3 , because the aldehydes themselves need multistep synthesis 10 .…”

Harnessing Photoexcited Redox Centers of Semiconductor Photocatalysts for Advanced Synthetic Chemistry

“…Recently, we developed a visible‐light‐induced radical strategy for the 1,2‐formylarylation of N ‐arylacrylamides using a carbazolic‐cyanoconjugated microporous polymer (CC‐CMP) as a metal‐free photocatalyst ( Figure ). [ 118 ] Here, photoexcited electrons were utilized to obtain the tert ‐butyloxy radical, which abstracted a 2‐C(sp 3 )−H of 1,3‐dioxolane to generate an alkoxyalkyl radical intermediate A. The radical addition of intermediate A to acrylamides followed by intramolecular cyclization, hole‐induced oxidation, and rearomatization resulted in dioxolane acetal intermediates.…”