An Efficient Synthesis of 3‐Substituted Isoquinoline and Pyridine Derivatives by Gold Catalyzed Intramolecular Cyclization from o‐Alkynyloximes

Abstract

A one‐pot reaction was developed efficiently by AuCl3 catalyzed intramolecular cyclization of aromatic o‐alkynyloximes and 2‐alkynylcycloalkene‐1‐carbaldoximes leading to the formation of isoquinoline and pyridine derivatives with high yields. This methodology has been applied for aromatic as well as aliphatic systems. Aromatic o‐alkynyloximes are benzene and naphthalene, whereas electron‐donating groups are 4‐methoxybenzene, 4‐methylbenzene, and 4‐methoxy‐5‐methylbenzene. There are electron‐withdrawing groups such as chloro and nitrobenzene o‐alkynyl oximes, and the same methodology has been successfully applied to pyridine and piperonal, which is also extended to aliphatic rings such as five‐member, six‐member, seven‐member, and eight‐member 2‐alkynylcycloalkene‐1‐carbaldoximes.

Harnessing the Potential of Electron Donor–Acceptor Complexes and N-Centered Radicals: Expanding the Frontiers of Isoquinoline Derivative Synthesis

“…Isoquinolines exhibit a diverse array of biological activities encompassing antitumor, analgesic, antifertility, antihistaminic, antimicrobial, and antiviral properties and demonstrating an ability to act as an antispasmodic or vasodilator. 6,7 Initially, isoquinolines were synthesized using Bischler− Napieralski 8 or Pomeranz−Fritsch 9,10 procedures, under harsh conditions and with low functional group compatibility. As a result of these limitations, chemists started exploring alternative strategies employing palladium-, 11−18 nickel-, 19 silver-, 20 gold-, 7,21 or rhodium-based 22 synthesis to overcome these challenges.…”

“…Among this class of compounds, isoquinolines represent a distinct category of six-membered N -heterocycles that occur naturally as alkaloid compounds. Isoquinolines exhibit a diverse array of biological activities encompassing antitumor, analgesic, antifertility, antihistaminic, antimicrobial, and antiviral properties and demonstrating an ability to act as an antispasmodic or vasodilator. , …”

“…Initially, isoquinolines were synthesized using Bischler–Napieralski or Pomeranz–Fritsch , procedures, under harsh conditions and with low functional group compatibility. As a result of these limitations, chemists started exploring alternative strategies employing palladium-, − nickel-, silver-, gold-, , or rhodium-based synthesis to overcome these challenges. While some of these methods required high temperatures, others needed stoichiometric amounts of metal catalysts. − Given the current challenges, there is indeed a pressing need for development of new methodologies to address these issues.…”

Synthesis of Isoquinolines and Related Heterocycles under Visible-Light Conditions

“…Some limitations such as harsh reaction conditions or poor functional group tolerance led chemists to develop new protocols. Thus, isoquinolines’ synthesis has then been largely developed with the use of transition metals such as palladium, − nickel, rhodium, − gold, , or silver . However, global warming effect and depletion of such metals lead us to develop greener methods.…”