N‐Heterocyclic Carbene Catalyzed Intramolecular Hydroacylation of Activated Alkynes: Synthesis of Chromones

Abstract

An organocatalytic intramolecular Stetter-type hydroacylation reaction between an aldehyde and an activated alkyne has been developed. This study induces salicylaldehyde-derived alkyne derivatives to assemble into a series of chromone derivatives using a catalytic amount of thiazoliumbased carbene catalyst.Keywords: chromones; hydroacylation; N-heterocyclic carbenes; organocatalysis; Stetter reaction Over the past few decades, the development of N-heterocyclic carbenes (NHC) has made important headways due to their extensive applicability in several reactions.[1] Besides the role as excellent ligands in the metal-catalyzed reactions, [2a-c] their ability to efficiently catalyze a number of organic reactions, most notably benzoin condensation, [2d-j] Stetter reaction, [3] transesterification [3h] and homo-enolate addition, [4] has contributed significantly to organic transformations. In 1973, Stetter established the first conjugate addition of aldehydes to a,b-unsaturated ester adopting the cyanide ion as the initial catalyst, [5a] and subsequently using a thiazolium-based carbene catalyst.[5b,c] The recent intermolecular variants of the Stetter reaction set in motion an expanding usage of NHCs as organocatalysts for carbon-carbon bond formation.[6] By exploiting an intramolecular Stetter reaction, Trost [7a] constructed a tricyclic system in order to synthesize hirsutic acid. Pioneering studies carried out by Ciganek, [7b] Enders [7c] and Rovis [7d,e] resulted in the development of intramolecular cyclizations as an access to various chromones. In addition, Glorius [8a,b] and She [8c] embarked on intramolecular acyl anion additions to unactivated olefin to construct the chromone scaffolds.Chromones are useful heterocyclic motifs found commonly in pharmaceutical compounds and they often exhibit fascinating therapeutic effects.[9] Our interest in drug discovery [10] motivated us to devise new methodologies for the chromone synthesis. Recently, we reported an NHC-catalyzed intramolecular crosscoupling between the aldehyde and the nitrile function to afford 3-aminochromones in high yields [11] [Scheme 1, Eq. (1)]. A comparison of this chemistry to that of the Stetter reaction [Scheme 1, Eq. (2)] prompted us to investigate the possibility of a newly designed carbon-carbon bond forming reaction Scheme 1. NHC-catalyzed C À C bond formation strategy.

Chromone: A Valid Scaffold in Medicinal Chemistry

“…In summary, the obtention of chromones via palladium-mediated catalys is a simple and high efficient approach. was recently proposed for the synthesis of 3-aminochromones and other 3-substituted chromones, (scheme 2.9) [273][274][275] . NHCs catalysts were used with the purpose of promoting the intramolecular cross coupling between the aldehyde and the nitrile function (Scheme 2.9 A) or to enhance the intramolecular reaction of the aldehyde with an activated alkyne (Scheme 2.9 B).…”

Synthesis and <i>in Vitro</i> Antibacterial Evaluation of Novel 4-Substituted 1-Menthyl-1,2,3-triazoles

“…Preparation of Mesylate 2 and Azide 3 Menthyl methanesulfonate (2) and menthyl azide (3) were synthesized according to the known methods reported in the literature. 27,28) Preparation of Propargylic Compounds 7a-c, 8a-i and 9a-c Compounds 7a-c, 8a-i and 9a-c 22,31,[40][41][42][43][44][45][46][47] were synthesized by propargylation of compounds 4a-c, 5a-i and 6a-c, respectively, according to a known procedure. 48) General Procedure for Preparation of Menthyl 1,4-Disubstituted 1,2,3-Triazole Derivatives (10a-c, 11a-i, 12a-c) Synthesis of the target compounds 10a-c, 11a-i and 12a- 10a-c, 11a-i, 12a-c).…”

Organocatalytic transformations of alkynals, alkynones, propriolates, and related electron-deficient alkynes

“…A remarkable example involving the use of alkynyl ketones and esters instead of ynals was reported by Liu and co-workers 35 in 2011. An intermolecular hydroacylation to prepare a novel synthesis of chromones 76 was described by using in this case the thiazolium salt 75 as the carbene precursor (Scheme 32).…”