Tunable Synthesis of 3-Hydroxylisoquinolin-1,4-dione and Isoquinolin-1-one Enabled by Copper-Catalyzed Radical 6-endo Aza-cyclization of 2-Alkynylbenzamide

Abstract

In this work, switchable synthesis of isoquinolin-1-one and 3-hydroxylisoquinolin-1,4-dione from 2-alkynylbenzamide is reported. The transformation works well with good yields and a broad reaction scope. The synthetic switch for providing isoquinolin-1-one and 3-hydroxylisoquinolin-1,4-dione is enabled by the use of a N2 or O2 atmosphere. Mechanism studies show that the reaction proceeds in a regioselective manner via a N-center radical 6-endo-dig aza-cyclization pathway.

Recent Advances in Copper‐Catalyzed C−N Bond Formation Involving N‐Centered Radicals

“…In 2019, a switchable synthetic strategy for preparing isoquinolin‐1‐ones and 3‐hydroxylisoquinolin‐1,4‐diones was developed by Qiu and co‐workers (Scheme 15). [26] In this work, different products were afforded from 2‐alkynylbenzamides in moderate to good yields based on the use of either N 2 or O 2 atmosphere. This protocol was highly regioselective, scalable to multigram quantities, and exhibited excellent functional group tolerance.…”

Comprehensive Strategies for the Synthesis of Isoquinolines: Progress Since 2008

“…[110] Liu et al described the synthesis of isoquinolin-1one 165 and 3-hydroxylisoquinolin-1,4-dione 166 under Cu-catalyzed reaction conditions from 2-alkynylbenzamide 164 via radical 6-endo azacyclization pathway (Scheme 88). [111] Recently, Lee et al investigated two distinctive transition-metal-mediated/catalyzed aerobic oxidation protocols towards the synthesis of isoquinolones 168 from 2-vinylbenzaldehydes 167 and aniline derivatives 12. The protocol is revealed to be proceeding via 6πelectrocyclization of 1-azatrienes resulting in 1,2dihydroisoquinoline intermediates, which on aerobic oxidation yields the product isoquinolone (Scheme 89).…”

“…described the synthesis of isoquinolin‐1‐one 165 and 3‐hydroxylisoquinolin‐1,4‐dione 166 under Cu‐catalyzed reaction conditions from 2‐alkynylbenzamide 164 via radical 6‐endo azacyclization pathway (Scheme 88). [111] …”

Photoredox‐Catalyzed Functionalization of Alkenes with Thiourea Dioxide: Construction of Alkyl Sulfones or Sulfonamides

“…On the other hand, some inexpensive and commercially available sulfur dioxide‐containing reductants, such as rongalite, sodium hyposulfite and thiourea dioxide, are widely used in the dye, rubber and bleaching industries . Additionally, as versatile reagents in synthetic chemistry, they have been developed as the source of sulfonyl compounds . Initially, sulfur dioxide‐ containing reductants were mainly used for electrophilic substitution reactions with alkyl halides to generate symmetric sulfone compounds .…”

“…Additionally, as versatile reagents in synthetic chemistry, they have been developed as the source of sulfonyl compounds . Initially, sulfur dioxide‐ containing reductants were mainly used for electrophilic substitution reactions with alkyl halides to generate symmetric sulfone compounds . In recent years, it has been discovered that sulfur dioxide radical anions derived from the interaction of sulfur dioxide anions with metal catalyst or photosensitizers could undergo radical coupling reactions with heteroaryl/aryl radicals to form heteroaryl/aryl sulfinates .…”