Direct Synthesis of Monofunctionalized Indolizine Derivatives Bearing Alkoxymethyl Substituents at C-3 and Their Benzofused Analogues

Abstract

[reaction: see text] Treatment of (Z)-2-pyridine and quinoline silylated vinylacetylenes at reflux with several alcohols in the presence of a suitable inorganic base (KOH, K2CO3, CsF, or KF) serendipitously gave 3-alkoxylmethylindolizines and the corresponding 1-alkoxymethylpyrrolo [1,2-a]quinolines and not the anticipated desilylated vinylacetylene derivatives. A mechanistic possibility for this unexpected chemical transformation is suggested.

Hydrohalogenation of Ethynylpyridines Involving Nucleophilic Attack of a Halide Ion

“…Haloalkene 4Eb was a viable substrate for Sonogashira coupling, affording corresponding enynes 15k and 15l (Scheme 5). 8,13 On the other hand, when trimethylsilylacetylene was used as a coupling partner, enyne 15m was not obtained, and desilylation occurred under the employed conditions. Instead, 3,3′-bis(indolizine) 16 was isolated as a result of double coupling and tandem cyclization (Scheme 6).…”

“…7 Wittig bromoolefination of pyridinecarbaldehyde leading to the synthesis of 2-(2-bromoethenyl)pyridine was also reported by Kaloko and Hayford. 8 However, these approaches suffer from the poor availability of the starting materials and low reaction efficiencies. There is no report regarding the preparation of 4 upon addition of hydrogen halide 2 to 1 , except for a single description, 9 which prompted us to study this reaction.…”

Synthesis of Isoxazolines and Isoxazoles Inspired by Fipronil

“…23 Sonogashira coupling with trimethylsilylacetylene followed by TMS deprotection provided phenylacetylenes 10 and 11. 24 These palladium couplings did not show any reactivity with the chloro substituents as had been observed in the Stille coupling, but the lower reactivity of the Sonogashira coupling reaction required the iodoarenes instead of the bromoarenes used previously in the styrene syntheses.…”

A Modular Synthesis of Polysubstituted Indolizines

“…Whereas indolizines devoid of electron‐withdrawing groups (EWGs) such as compounds 4a – l can be sensitive towards aerial oxidation, indolizine‐3‐carbonitriles 6a – d are much more stable and can be purified and stored without special precautions 9f,21,22…”