Synthesis of Polycyclic Quinazolinones through C(sp³)−H Functionalization of Inert Alkanes or Visible‐Light‐Promoted Oxidation Decarboxylation of N‐Hydroxyphthalimide Esters

Abstract

Two novel C(sp 3 )À H functionalization of inert alkanes and visible-light promoted oxidation decarboxylation of N-hydroxyphthalimide (NHP) esters to access polycyclic quinazolinones have been described. These methods do not involve metal catalysts and are carried out in water or water/DMSO media. The wide substrate scope, even including the seven-membered ring under mild reaction conditions, demonstrate the practicability of these strategies.[a] W.

NaI/PPh3-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

“…All of these outcomes indicate that a radical species should be involved in this decarboxylative cascade cyclization towards oxindoles under NaI/PPh 3 catalysis. Thus, the mechanism should run in a similar fashion to related well-documented previous reports [ 54 , 68 – 77 ], through a light-induced, phosphine-assisted, intermolecular electron transfer from sodium iodide to the redox-active ester.…”

“…In a broader context, phosphine organocatalysis is probably still underappreciated in organic synthesis, and could lead to important future synthetic developments [61][62][63][64][65][66][67]. The NaI/PPh 3 system has been further broadly applied to the functionalization of alkenes [68][69][70], as well as to decarboxylative C(sp 3 )-X bond formation [71], cyclization of 1,7-enynes [72,73] and other reactions [74][75][76][77]. Inspired by these advances, we developed here a visible light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides under NaI/PPh 3 catalysis, for the most efficient and practical synthesis of quaternary oxindoles (Scheme 1b and 1c).…”

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

“…Wei and co‐workers reported the synthesis of alkyl‐substituted polycyclic quinazolinones via the C(sp 3 )−H functionalization of inert alkanes. The oxidative decarboxylation of N ‐hydroxyphthalimide (NHP) esters was also achieved under visible‐light promoted conditions (Scheme 48d) [85] …”

“…The oxidative decarboxylation of Nhydroxyphthalimide (NHP) esters was also achieved under visible-light promoted conditions (Scheme 48d). [85] Not only carbon-centered radical intermediates, other radicals can also undergo similar transformations to generate differently functionalized polycyclic quinazolinones. In 2021, Jin and co-workers utilized sulfonyl chlorides as sulfonyl radical sources to give sulfonylated ring-fused quinazolinones (Scheme 49a).…”

Cyclizations of Alkenyl(Alkynyl)‐Functionalized Quinazolinones and their Heteroanalogues: A Powerful Strategy for the Construction of Polyheterocyclic Structures

“…of KI and 10 mol% of PPh 3 produces 3(6)‐alkyl substituted pyrrolo(pyrido)quinazolinones 86 in good yields (Scheme 23). [111] At the first step of the conversion, a photoinduced single electron transfer (SET) from the iodide anion to NHP‐ester occurs thus generating an alkyl radical, which selectively binds to the C=C bond of 85 to form radical intermediate A . Then the radical site of A attacks the endocyclic N=C bond giving rise to cyclic intermediate B ; the latter undergoes a 1,2‐H shift to provide radical C , which is SET‐oxidized and deprotonated to target products 86 .…”