Synthesis of Tetracyclic Quinazolinones Using a Visible-Light-Promoted Radical Cascade Approach

Abstract

A practical approach for the synthesis of tetracyclic pyrroloquinazolines using photoredox strategy has been developed. The visible-light-promoted intramolecular single-electron-transfer process between photocatalyst and N-(2-iodobenzyl)-N-acylcyanamides is considered to be involved in this transformation. Targeted pyrroloquinazoline derivatives (15 examples) are presented in good isolated yields (30%-88%).

Synthesis of N-Heterocycles via Transition-Metal-Catalyzed Tandem Addition/Cyclization of a Nitrile

“…Yu later modified Malacria's 46 reaction conditions for the synthesis of quinazolines (see Scheme 37) from a stoichiometric reaction to catalysis by using fac-Ir(ppy) 3 as the photocatalyst (Scheme 39). 52 Scheme 39 Ir-catalyzed tandem cyclizations through the radical addition of a nitrile to form pyrroloquinazolines fac-Ir(ppy) 3 as the photocatalyst is also able to be utilized for the synthesis of phenanthridinones. In 2017, Sun reported an Ir-catalyzed tandem radical cyclization to form phenanthridinones through the radical addition of a nitrile (Scheme 40, a).…”

Recent Advances in Radical‐Enabled Bicyclization and Annulation/1,n‐Bifunctionalization Reactions

“…[34] Subsequently, Yu'sg roup employed visible-light-promotedp hotoredox catalysis to improve this transformation (Scheme 16). [35] Moreover,F ensterbank, Malacria, and co-workers also introduced azides into N-acyl cyanamide molecules and subjected these substrates to the AIBN/Bu 3 SnH system for the creationo f polycyclic fused quinazolinone derivatives 62 (Scheme 17). [36] The authors proposed ar eaction mechanism that involved in situ radicalg eneration,a ddition of the radical to the CN triple bond, intramolecular 5-exo-dig cyclization,and aromatization to produce an imine radical and, finally,t he quinazolinone derivative( Scheme17).…”

“…In 2007, Malacria and co‐workers reported an AIBN/Bu 3 SnH‐initiated radical cascade cyclization reaction of N‐( 2‐iodobenzyl)‐ N ‐acylcyanamides for the formation of pyrroloquinazolines 60 and the total synthesis of luotonin A (Scheme ) . Subsequently, Yu′s group employed visible‐light‐promoted photoredox catalysis to improve this transformation (Scheme ) . Moreover, Fensterbank, Malacria, and co‐workers also introduced azides into N ‐acyl cyanamide molecules and subjected these substrates to the AIBN/Bu 3 SnH system for the creation of polycyclic fused quinazolinone derivatives 62 (Scheme ) .…”

Synergistic Effect between Ultrasound Irradiation and Na 2 CO 3 in N ‐Acylation Reaction: Applied for the Synthesis of Novel N ‐Acylcyanamide Derivatives

“…On the other hand, using the characteristic structure of N ‐acylcyanamides in organic synthesis can potentially generate biologically active nitrogen‐containing heterocycles (Scheme )In general, the reactivity N ‐acylcyanamides can be assessed by focusing on radical reactions. For example, these compounds can act as radical precursors for the preparation of quinazolinone moiety . Furthermore, radical synthesis of guanidines and acylguanidines from N ‐acylcyanamides has also been reported .…”

“…Taking advantage of radical reactions of N ‐acylcyanamides, several types of these materials have been constructed. This scaffold typically prepared through the N ‐acylation of cyanamide salts, base‐promoted N ‐acylation of cyanamides, two‐step sequence of cyanation/acylation, or acylation/cyanation of amines . Thus, the N ‐acylation of cyanamides seems to be an efficient and general strategy to prepare these materials.…”