Mild Regiospecific Synthesis of 1-Alkoxy-isochromenes Catalyzed by Well-Defined [Silver(I)(Pyridine-Containing Ligand)] Complexes

Abstract

The synthesis of 3-substituted-1-alkoxyisochromenes starting from 2-alkynylbenzaldehydes and different alcohols is reported. The reaction is catalyzed by a silver(I) complex with an original macrocyclic pyridine-containing ligand. The approach is characterized by absolute regioselectivity, mild reaction conditions, good to excellent reaction yields, cleanness of the reaction, and reduced purification steps. The reaction mechanism was investigated by in-depth (1)H NMR experiments and an aimed "trapping" experiment.

Organometallic Reactivity of [Silver(I)­(Pyridine‐Containing Ligand)] Complexes Relevant to Catalysis

“…The η 2 alkyne coordinated complex 5 shows the biggest effects, with H i at δ = 7.93 ppm, which is even lower than that of the free ligand 1c; this probably depends on the different conformations that are accessible to the naphthyl moiety in the free ligand to relieve steric crowding. Alcohols have been demonstrated to be suitable reagents in the domino synthesis of isochromenes catalyzed by silver complexes 2b, [17] but in some cases we observed a quite prolonged induction time. Thus, we were intrigued to study the coordination of 2-propanol to silver complex 2b 1 .…”

“…Silver complexes 2 were easily obtained as white crystals in yields up to 91 % by precipitation, concentrating the solvent, and adding nhexane. Complexes 2a 1-3 and 2c 1,2 have been already described, [17,18] and experimental details for all others complexes can be found in the Experimental Section and in the Supporting Information. All the obtained silver complexes 2 have been fully characterized by 1 H and 13 C NMR spectroscopy, ESI-MS, and IR and UV/Vis spectroscopy.…”

“…Concerning the catalytic applications we previously reported for these compounds, [17,18] the interactions with alkynes are those of greatest interest. We found that 2c 1 reacted with a terminal alkyne, such as phenylacetylene, to give silver phenylacetylide 4 and the protonated ligand 3, which partially precipitated as the tetrafluoroborate salt.…”

“…The silver(I) complexes with pyridine-containing ligands, [Ag I (Pc-L)], have already been demonstrated as active catalysts for some domino and multicomponent reactions, such as the synthesis of 1-alkoxyisochromenes [17] and the A 3 -coupling. [18] We have reported here their rich coordination chemistry with special emphasis on their behavior with reagents commonly employed in the above-mentioned reactions.…”

“…[16] We have recently demonstrated that the sil-ver(I) complexes of achiral Pc-L ligands are effective catalysts in the regiospecific synthesis of 1-alkoxy-isochromenes under mild reaction conditions. [17] The same silver(I) catalysts have shown a good catalytic activity in the microwaveenhanced synthesis of propargylamines starting from aldehydes, terminal alkynes, and amines (A 3 -coupling). [18] The great advantage of the [Ag I (Pc-L)] complexes with respect to simple silver salts, is their enhanced stability and the ease of handling.…”