Synthesis of 4-(1H-isochromen-1-yl)isoquinolines through the silver-catalysed homodimerization of ortho-alkynylarylaldehydes and subsequent condensation of the 1,5-dicarbonyl motif with NH₃

Abstract

We demonstrate a strategy that can provide isochromenes with an electron-deficient isoquinoline unit. The reactions feature simple operations, mild conditions and high yields.

AgNTf2-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives

“…Recently, Zhu’s group developed a tandem 1,3‑dipolar cycloaddition/cyclopropanation silver-catalyzed reaction of enynals with alkenes [17]. In our previous studies, this silver carbene species could be also involved mechanistically in the Ag-mediated reaction of enynals with conjugated dienes [18] and the homodimerization of enynals [19–20]. So, the studies on the reactions of alkynes involving the generation of silver carbene species from non-diazo precursors are of great value for getting some insight into silver-carbene chemistry.…”

Gold-Catalyzed Enynal and Enynol Coupling by Selectively Steering Two Transient Vinyl-Gold Intermediates

“…Moreover, we performed a gram-scale reaction of 1a with 2a to showcase the scalability of this method. This reaction proceeded smoothly to give 3a in 80% isolated yield (1.14 g) and a tiny amount dimerization byproduct of isochromenylium 14 which not observed in our reaction system before. We postulated that the relatively low yield for this system might arise from some unidentified oligomers or degradation mixture rather than such a dimer, as the NMR spectra obtained from the minor traces on the preparative TLC have bad resolution.…”

“…Luckily, the target product 3-phenyl-1-(2-phenylbenzofuran-3-yl)-1H-isochromene (3a) was formed in 30% yield under the PPh 3 AuCl/ AgBF 4 (5 mol %) catalyst, without observing any dimerization product of isobenzopyrylium (entry 1). 14 Various silver salts, known to be efficient for cycloisomerization reactions of oalkynylbenzaldehydes, were then tested. When we used AgOTf and AgNTf 2 , the desired product 3a was obtained in 8% and 6% yields, respectively (entries 2 and 3).…”

“…With these considerations in mind, we commenced the study by surveying the model reaction between 2-(phenylethynyl)­phenol 1a and 2-(phenylethynyl)­benzaldehyde 2a under gold-catalysis conditions (Table ). Luckily, the target product 3-phenyl-1-(2-phenylbenzofuran-3-yl)-1 H -isochromene ( 3a ) was formed in 30% yield under the PPh 3 AuCl/AgBF 4 (5 mol %) catalyst, without observing any dimerization product of isobenzopyrylium (entry 1) . Various silver salts, known to be efficient for cycloisomerization reactions of o -alkynylbenzaldehydes, were then tested.…”