Cycloisomerization of Pyridine‐Substituted Propargylic Alcohols or Esters To Construct Indolizines and Indolizinones

Abstract

Nitrogen‐containing heterocycles are found in a vast number of natural products and biologically active compounds, and have attracted a lot of attention. Among all the reported methods, cycloisomerization transformations involving the activation of alkynes with the aid of transition metals are a very active area in synthetic organic chemistry. This review covers the most important recent advances in the use of metal‐catalyzed or metal‐free cycloisomerizations for the preparation of indolizines and indolizinones from starting substrates consisting of pyridine‐containing propargylic esters or alcohols. Cycloisomerization transformations to heterocycles are very efficient and atom‐economic, and we hope that this review will result in further focused research to widen the application of indolizines and indolizinones.

Au(I)-Catalyzed Synthesis of Trisubstituted Indolizines from 2-Propargyloxypyridines and Methyl Ketones

“…2 Beyond the classical strategies of Scholtz 3 and Tschichibabin, 4 methods for the synthesis of the indolizine core largely fall into one of three categories: 1,3-dipolar cycloaddition to pyridinium ions, 5 cyclocondensations, 6 or transition metal catalyzed cycloisomerization reactions. 7 As these are the common approaches to indolizine formation, we were surprised to observe trisubstituted indolizine 4 as a significant byproduct during the synthesis of pyridonyl enol ether 2 from 2-propargyloxypyridine 1 (Scheme 1). 8 To the best of our knowledge, this is the first synthesis of trisubstituted indolizines from a 2-alkoxypyridine, and it represents a unique approach to the indolizine core.…”

Straightforward Access to 2-Iodoindolizines via Iodine-Mediated Cyclization of 2-Pyridylallenes

“…Although there is growing interest in accessing 1,2,3-trisubstituted indolizines, to the best of our knowledge only Kim and colleagues have proposed a method to synthesize 1,3-disubstituted 2-iodoindolizines from propargylic acetates. , The iodine substituent at the 2-position should allow postfunctionalization through commonly used transition-metal-catalyzed cross-coupling reactions or a radical pathway. Also, a brief literature survey shows that pyridylallenes are valuable intermediates for the synthesis of indolizines via 5-endo-trig cyclization reaction under electrophilic activation. , …”

Oxygen as a Heteroatom in Propargylic Alcohols: Reactivity, Selectivity, and Applications

“…The applications of propargylic alcohols [1] in many useful transformations, significant utilization in total synthesis, [2][3][4][5][6][7]9] and in construction of many heterocyclic compounds [8][9] and their derivatives have gained much attention and have been extensively investigated. Recent developments on the chemistry of propargylic alcohols and their derivatives disclosed a variety of highly efficient Lewis acid-catalyzed cascade reactions based on Meyer-Schuster rearrangement [10][11][12] (MSR) of propargylic alcohols, [3,3] rearrangement of propargylic acetates and intramolecular cyclization of propargylic alcohols, tethered with nucleophiles.…”