Cyanoquinolines and Furo[3,4-b]quinolinones Formation via On-The-Spot 2,3-Functionalization of Quinolines with Cyanopropargylic Alcohols

Abstract

A convenient approach to 2-(1-ethoxyalkoxy)-3-cyanoquinolines (in up to 50% yields) has been developed. The approach comprises functionalization of quinolines with acetals of cyanopropargylic alcohols (KOH/H2O/MeCN, 55–60 °C) followed by their transformation to furo­[3,4-b]­quinolinones (in up to 98% yields) via the sequential removal of acetal protection and intramolecular cyclization/hydration (7% aqueous HCl, acetone, 20–25 °C).

Organometallic Reagents: Efficient Tools for the Synthesis of Fused Pyridinyl‐Lactones

“…However, regardless the procedure used, no trace of the 3-(pnitroaryl)benzothienyl-lactone 13 e was detected, and the 3-(mnitroaryl)-or 3-(p-trifluoromethylaryl)-analogs 13 f et 13 h were provided in disappointing yields (33 and 28 % yield respectively, entries 8 and 11, Table 4). In addition to 16 which was still isolated but in lower yield, the hydroxy-ester derivatives 19 ef, h, 20-21 were isolated in very good yields (up to 83 %, entries 5,7,10,17 and 18,Table 4). Whereas from nicotinic substrate 1 b, lactonization occurred spontaneously after the electrophile trapping step, here, in the presence of electronenriched heterocyclic scaffolds, the expected subsequent cyclization appeared as the limiting step.…”

“…[3b] More recently furo [3,4-b]quinolinones were synthesized from 2-(1-ethoxyalkoxy)-3-cyanoquinolines via sequential removal of acetal protection and intramolecular cyclization/hydration (Scheme 1C). [7] Lately, a regioselective synthesis of furanonefused isoquinoline was developed using Rh III catalyst involving a one pot sequence of CÀ H activation, regioselective annulation and lactonization (Scheme 1D). [8] Obviously, it appears that a straightforward strategy allowing a general access to various 3-or 3,3-disubstituted pyridinyllactones is not available yet.…”

“…Within the framework of the synthesis of pyridopyridazinones and pyridazinthiones in a patent from 1992, pyridinyl‐lactones 3‐substituted were obtained from pyridoacid ester and substituted benzaldehyde by heating at 150–200 °C (Scheme 1B) [3b] . More recently furo[3,4‐ b ]quinolinones were synthesized from 2‐(1‐ethoxyalkoxy)‐3‐cyanoquinolines via sequential removal of acetal protection and intramolecular cyclization/hydration (Scheme 1C) [7] . Lately, a regioselective synthesis of furanone‐fused isoquinoline was developed using Rh III catalyst involving a one pot sequence of C−H activation, regioselective annulation and lactonization (Scheme 1D) [8] …”

δ-Keto Aminoacrylonitriles and δ-Keto Aminoenones from 1-Pyrrolines, Cyanoacetylenes, and Acetylenic Ketones

“…29 2-Methoxy-1-pyrroline 1e was prepared from NH-pyrrolid-2-one by the reaction with dimethyl sulfate. 30 Acetals of cyanopropargylic alcohols 2a-c, 31 acylacetylenes 6b,c, 32 and 6d,e 33 were prepared according to the described procedures. Acylethynylpyrroles 8a,b, 10 were obtained by the literature method 27a from the corresponding pyrroles and acylhaloacetylenes in the presence of Al 2 O 3 .…”