Metal‐free and One‐pot for the Synthesis of Indolo[2,1‐a]isoquinoline Aldehyde via a Free Radical Cascade Pathway followed by Direct Hydrolyzation

Abstract

As one of the most versatile intermediate group in synthetic chemistry, the introduction of an aldehyde group into a specific moiety is important for the transformation of molecular structures. Herein, we provided a metal-free, regioselective and one-pot formylation of the indolo[2,1a]isoquinoline moiety. This strategy features an oxidative coupling process using commercially available 1,3-dioxolane as a formylated reagent followed by direct hydrolyzation without a separation process. This reaction can be carried out under common reaction conditions and displays broad functional group tolerance.

Synthesis of ester-functionalized indolo[2,1-a]isoquinolinesviairon-catalyzed radical cascade cyclization of 2-aryl-N-acryloyl indoles with carbazates

“…Based on the experimental results and previous reports, 6–11,13–20 a plausible mechanism for this transformation is proposed, as shown in Scheme 2. Initially, TBHP decomposed to generate the tert -butoxyl and tert -butylperoxy radicals with the assistance of Fe( ii ).…”

“…Indolo[2,1- a ]isoquinoline derivatives are important nitrogen-containing heterocycles and are commonly found in many organic synthetic intermediates, biologically active natural products, pharmaceuticals, and functional materials. 12 Recently, considerable effort has been devoted to the construction of structurally diverse indolo[2,1- a ]isoquinolines via a radical addition/cyclization process, including arylation, 13 alkylation, 14 sulfonylation, 15 acylation, 16 thiolation, 17 germylation, 18 selenylation 19 and phosphonation 20 (Scheme 1a). However, the application of this strategy for the synthesis of ester-functionalized indolo[2,1- a ]isoquinolines utilizing easily accessible and safe carbazates as the alkoxycarbonyl radical precursor has not been achieved.…”

The Synthesis of 5,6‐dihydrobenzo[4,5]imidazo[2,1‐a]isoquinoline Derivatives via Metal‐Free Radical Cascade Pathway

“…A possible reaction mechanism is proposed on the basis of the above experimental observations and previous literature reports (Scheme 7). [4b–d,5] Initially, benzoate radical is formed by the thermal cleavage of BPO [6] . Then, the 1,3‐dioxolane is activated by the benzoate radical to generate radical A .…”

Radical Cascade Cyclization of Alkene‐Tethered Compounds: Versatile Approach towards Ring‐Fused Polycyclic Structures

“…In 2020, Zhang and co‐workers reported the introduction of cyclic ethers into the benzimidazo[2,1‐ a ]isoquinolin‐6(5 H )‐one motif under BPO‐promoted metal‐free conditions (Scheme 77a) [135] . When 1,3‐dioxolane and 2‐methyl‐1,3‐dioxolane were used, the in situ hydrolyzation afforded corresponding aldehyde and ketone derivatives (Scheme 77b) [136] …”

“…[135] When 1,3-dioxolane and 2-methyl-1,3-dioxolane were used, the in situ hydrolyzation afforded corresponding aldehyde and ketone derivatives (Scheme 77b). [136] In 2020, Guan, He and co-workers developed the synthesis of CF 3 -substituted benzimidazo[2,1-a]isoquinolin-6(5H)-ones from N-methacryloyl-2-phenylbenzoimidazoles with trifluoromethanesulfonyl chloride under redox-neutral photocatalytic conditions (Scheme 78a). [137] Moreover, BrCH 2 CN and BrCF 2 COOEt were also suitable radical precursors to give CH 2 CNand CF 2 COOEt-containing benzimidazo[2,1-a]isoquinolin-6(5H)- ones via the cleavage of CÀ Br bond.…”