Stereoselective synthesis of thiazino[4,3-a] indoles using the thia-Pictet-Spengler reaction of indoles bearing N-tethered thiols and vinylogous thiocarbonates

Lewis Acid Promoted Oxonium Ion Driven Carboamination of Alkynes for the Synthesis of 4-Alkoxy Quinolines

Metal-free Hydroalkoxylation-Formal [4+2] Cycloaddition Cascade for the Synthesis of Ketals

Metal-Free Intramolecular Hydroalkoxylation of Alkyne: Recent Advances

Hydroalkoxylation of alkyne offers a unique platform to rapidly access structurally complex and densely functionalized oxygen-bearing heterocycles. Further, to enhance the synthetic utility, various cascade reactions including hydroalkoxylation have been reported in both stereo- as well as enantioselective manner under metal and metal-free conditions. A collection of the most representative and recent methods employing metal-free hydroalkoxylation events are presented in this review article.

Transition Metal Catalyzed Hydroalkoxylation of Alkynes: An Overview

Oxygen-bearing motifs, mainly the congener heterocycles are ubiquitous due to their presence in various natural products and bioactive scaffolds. Although in literature, several strategies have been developed for their synthesis, hydroalkoxylation of alkynes has come forward as a method of choice and has been used extensively. In particular, hydroalkoxylation of alkynes has gained enormous attention from the synthetic community due to the rapid access to a very useful and reactive synthetic intermediate like ‘enol ether’. Furthermore, to manifold the utility of these methods, reports have been developed elaborating the generation of ‘enol ether’ using hydroalkoxylation and their usage in various reactions in a cascade or tandem manner. This review focuses on recent development in the hydroalkoxylation of alkynes for the synthesis of oxygen-containing entities.

Formal [4+2] Cycloaddition of o-Aza-Quinone Methide for the Synthesis of 1,4-Heterocycle-Fused Quinolines

A protocol involving intramolecular formal [4+2]-cycloaddition of in?situ generated o-aza-quinone methide for the facile synthesis of 1,4-heterocycle-fused quinoline motifs is demonstrated. The cascade involved tandem C?O, C?C, and C?N bond formation and also exhibited excellent functional group tolerance. Enantiomerically enriched 1,4-oxazepino quinolines were synthesized using alkynols derived from L-amino acids. The sulfoxide embedded quinolines were transformed to pentacyclic 1,4-thiepino tethered indeno-quinoline scaffolds via Pummerer cyclization.

Lewis Acid Mediated “endo-dig” Hydroalkoxylation–Reduction on Internal Alkynols for the Stereoselective Synthesis of Cyclic Ethers and 1,4-Oxazepanes

Lewis acid mediated 5/6/7-endo-dig hydroalkoxylation–reduction cascade on internal alkynols gave an expedient, stereoselective synthesis of cyclic ethers and 1,4-oxazepanes. The strategy has been extended to the first examples of hydroalkoxylation–alkyne Prins-type cyclization cascade of alkyne-tethered alkynols, giving access to oxa-bicyclic scaffolds. This method was used as the key step in the stereoselective total synthesis of calyxolane A-B, as well as (±)-centrolobine and its homologue.

Domino Hydroalkoxylation-[4+2]-Cycloaddition for Stereoselective Synthesis of 1,4-Heterocycle-Fused Chromenes: Rapid Access to the [6-6-7-6] Tetracyclic Core of Cytorhizhins B–D

A substrate dependent regio- and stereoselective domino hydroalkoxylation-formal cycloaddition is described for the facile synthesis of linear as well as spirocyclic 1,4-heterocycle-fused chromenes. The developed hydroalkoxylation cascade offered a quick access to the [6-6-7-6] tetracyclic framework of cytorhizhins B–D.

Expeditious diastereoselective synthesis of medium ring heterocycle-fused chromenes via tandem 8/9-endo-dig and 8-exo-dig hydroalkoxylation-formal-[4 + 2] cycloaddition†

The first examples of highly diastereoselective tandem 8/9-endo-dig and 8-exo-dig hydroalkoxylation-formal-[4 + 2] cycloaddition are described for the synthesis of medium ring heterocycle-fused chromenes. TMS-alkynols preferred the exo-dig mode of hydroalkoxylation over the endo-dig mode leading to spiro-cyclic chromenes. The method could be used for the synthesis of linearly-fused ladder-like polyethers. A thia-heterocycle-fused chromene could be transformed into a complex bridged tricyclic ketal by a tandem carbene-insertion-[2,3]-sigmatropic shift.

The first examples of highly diastereoselective tandem 8/9-endo-dig and 8-exo-dig hydroalkoxylation-formal-[4 + 2] cycloaddition are described for the synthesis of medium ring heterocycle-fused chromenes. TMS-alkynols preferred the exo-dig mode of hydroalkoxylation over the endo-dig mode leading to spiro-cyclic chromenes. The method could be used for the synthesis of linearly-fused ladder-like polyethers. A thia-heterocycle-fused chromene could be transformed into a complex bridged tricyclic ketal by a tandem carbene-insertion-[2,3]-sigmatropic shift.