Intramolecular Heterocyclization of O-Propargylated Aromatic Hydroxyaldehydes as an Expedient Route to Substituted Chromenopyridines under Metal-Free Conditions

Abstract

A concise and regioselective approach to the synthesis of chromenopyridine and chromenopyridinone derivatives was developed. The synthetic strategy relies on the O-propargylation of aromatic hydroxyaldehydes followed by reaction with propargylamine. The intramolecular cycloaddition reaction between the alkyne and azadiene, which is formed as an intermediate, furnished the desired skeletons.

A Concise Review on Pyridocoumarin/Azacoumarin Derivatives: Synthesis and Biological Activity

“…Keskin et al . developed a brief, high yielding and regioselective approach for the synthesis of pyridocoumarin derivatives 295 using intramolecular cycloaddition reaction between the alkyne and azadiene groups of 292 , which is formed as an intermediate from aromatic hydroxyaldehydes 264 , propargyl bromide 288 and propargyl amine 290 and followed by oxidation with chromic acid (Scheme ).…”

Regioselective Synthesis of Benzo[h][1,6]‐naphthyridines and Chromenopyrazinones through Alkyne Cyclization

“…Pale brown viscous oil (0.30 g, 68 %). (ddd, J 8,7 = 8.1,J 8,9 = 7.1,J 8,10 = 1.4 Hz,1 H,3 H,arom),2 H,arom), 2.35 (s, 3 H, 1′-H) ppm. s,2 H,8.17 (dd,J = 7.9 and 1.5 Hz,2 H,arom),7.91 (dd,J 6,5 = 7.7,J 6,4 = 1.3 Hz,1 H,7.70 (d,J = 7.7 Hz,2 H,arom),1 H,arom),3 H,arom),7.30 (t,J = 7.6 Hz,1 H,4.35 (s,4 H, ppm.…”

“…[5] Pierre et al reported that naphthyridine derivative 6 inhibits protein kinase CK2, which is relevant for the treatment of cancer [6] (Figure 2). [8] Chromenopyridine scaffold 9 was obtained in just two steps, and the key reaction was an alkyne cyclization [9] which took place without metals to promote the process. [7] Most of the procedures involve many steps and require complicated starting materials.…”

“…Recently, we designed a new method for the synthesis of chromenopyridine derivative 9, using an intramolecular [4+2] Diels-Alder cycloaddition reaction (Scheme 1). [8] Chromenopyridine scaffold 9 was obtained in just two steps, and the key reaction was an alkyne cyclization [9] which took place without metals to promote the process. Scheme 1.…”

Enaminones as Synthons for a Directed C−H Functionalization: RhIII‐Catalyzed Synthesis of Naphthalenes

“…And the hydroxy group provided a handle for the generation of ethers (7 a and 8 a) through reaction with a bromo-containing molecule. [14] Significantly, participation of both aldehyde and hydroxy groups enabled the synthesis of another ring structure on the original naphthalene framework (9 a). [15] In summary, we have proposed an enaminone-directed CÀ H functionalization method and demonstrated its utility in the Rh III -catalyzed synthesis of naphthalenes, through coupling with either alkynes or a-diazo-b-ketoesters.…”