Versatile Synthesis of Isoquinolines and Isochromenes by Pd‐Catalyzed Oxidative Carbonylation of (2‐Alkynyl)benzylideneamine Derivatives

Abstract

Keywords: Alkynes / Carbonylation / Cyclization / High-pressure chemistry / Palladium Isoquinoline-4-carboxylic esters 3 and isochromene-4-carboxylic esters 4 have been conveniently prepared by direct PdI 2 -catalyzed oxidative heterocyclization/alkoxycarbonylation of readily available (2-alkynylbenzylidene)amine derivatives. In particular, (2-alkynylbenzylidene)(tert-butyl)-amines 2 selectively afforded isoquinoline derivatives 3 by N-cyclization, whereas N-(2-alkynylbenzylidene)-NЈ-phenylhydrazines 5 led to the formation of isochromenes 4

Synthesis of Functionalized Heterocycles via Oxidative Carbonylation

“…In 2011, they prepared isoquinoline-4-carboxylic esters and isochromene-4-carboxylic esters by palladium-catalyzed oxidative carbonylation of (2-alkynylbenzylidene)amine derivatives. Isoquinoline derivatives were obtained from (2-alkynylbenzylidene)(tert-butyl)amines through N-cyclization in the presence of dehydration agent, while isochromenes were obtained from N-(2-alkynylbenzylidene)-N 0 -phenylhydrazines through O-cyclization ensuing from water attack on the imino group (Scheme 28) [91].…”

Oxidative Carbonylation as a Powerful Tool for the Direct Synthesis of Carbonylated Heterocycles

“…Synthesis of indole-3-carboxylates 6 by PdI 2 /KI-catalysed oxidative 5-endo-dig heterocyclization/alkoxycarbonylation of 2-alkynyl anilines 5, each containing an internal triple bond and a secondary amino group. [14] www.eurjoc.org Scheme 10. In fact, 2-ethynylanilines possessing a terminal triple bond and a primary or a secondary amino group are known to lead to dihydroindol-2-one derivatives, [10] whereas 2-alkynylanilines with an internal triple bond and a primary amino group afforded acyclic carbamates [10] through the intermediate formation of isocyanates.…”

“…In fact, 2-ethynylanilines possessing a terminal triple bond and a primary or a secondary amino group are known to lead to dihydroindol-2-one derivatives, [10] whereas 2-alkynylanilines with an internal triple bond and a primary amino group afforded acyclic carbamates [10] through the intermediate formation of isocyanates. [14] Interestingly, N-[(2-alkynyl)benzylidene]-NЈ-phenylhydrazines 14 (Scheme 12) underwent O-cyclization as a result of water attack on the imino groups of the substrates, with formation of isochromene-4-carboxylates 15. PdI 2 /KI-catalysed oxidative carbonylation of these, carried out in the presence of an alcohol as external nucleophile and of trialkyl orthoformate as dehydration agent (to avoid substrate hydrolysis), directly afforded 1-(alkoxyarylmethyl)indole-3-carboxylates 9 through a multicomponent cascade process (Scheme 9).…”

“…[11] Interestingly, the formation of particular 2-alkynyl aniline intermediates -[(alkoxycarbonyl)(2-alkynylaryl)]amines 8 (Scheme 9) -could be achieved in situ from 2alkynylaniline-imines 7. [14] With particular substrates, the heterocyclization/alkoxycarbonylation process is accompanied by dehydration, triggered by aromatization. [12] Scheme 9.…”

Chalcogenoalkynes: Precursors for the Regioselective Preparation of 2‐Chalcogeno‐1‐halonaphthalenes through [4+2] Cycloaddition

“…[7] For the preparation of chalcogenoalkynes, we first generated the lithium acetylide intermediate by reaction of terminal alkynes with 1 equiv. The required precursors o-alkynylbenzaldehydes 1a-c were synthesized in good yields by the reaction of appropriate 2-bromobenzaldehydes with terminal alkynes under Sonogashira conditions.…”