‘One-pot’ Synthesis of Dihydrobenzo[4,5][1,3]oxazino[2,3-a] isoquinolines via a Silver(I)-Catalyzed Cascade Approach

Abstract

An efficient approach for the synthesis of biologically interesting fused tetracyclic isoquinolines in high yields and with a broad substrate scope has been developed. The strategy features an AgNO3 catalyzed ‘one-pot’ cascade process involving formation of two new C–N bonds and one new C–O bond.

[Ag(PcL)]‐Catalysed Domino Approach to 6‐Substituted Benzoxazino Isoquinolines

“…1 H NMR (300 MHz, CDCl 3 ): δ = 7.41 (d, J = 7.4 Hz, 1H), 7.32 (t, J = 7.4 Hz, 1H), 7.20 (m, 2H), 7.08 (m, 5H), 6.92 (t, J = 7.1 Hz, 1H), 6.81 (t, J = 7.7 Hz, 1H), 6.25 (d, J = 8.0 Hz, 1H), 6.08 (s, 1H), 5.95 (s, 1H), 5.25 (d, J = 14.6 Hz, 1H), 5.09 (d, J = 14.6 Hz, 1H), 2.33 (s, 3H). The spectroscopic data are in agreement with literature findings …”

“…According to literature findings, , and based on our results, a plausible reaction mechanism is proposed as depicted in Scheme . The very first step is the condensation between the benzaldehydes 1 and γ‐amino alcohols 2 to give the imine intermediate I .…”

“…Within a more general study on cascade reaction of o ‐alkynylbenzaldehydes and aromatic amines containing tethered nucleophiles, the authors reported a single example of gold(I) chloride catalysed synthesis of 12‐phenyl‐benzoxazino isoquinoline at 80 °C in DCE (Scheme a). Li and co‐workers in early 2013 widened the scope of the approach performing the reaction with silver nitrate as catalyst at 80 °C in toluene, yielding the desired adducts in fair to very good yields (Scheme b). A couple of months later, Verma and co‐workers, independently reported a very similar AgNO 3 ‐based approach, enhanced by the use of water as solvent, which needed a higher catalyst loading at the same temperature (80 °C) (Scheme c).…”

An Overview of Ag‐catalyzed Synthesis of Six‐membered Heterocycles

“…Later, a silver nitrate‐catalyzed one‐pot synthesis of dihydrobenzo[4,5][1,3]oxazino‐[2,3‐ a ]isoquinolines 84 was developed by Zhou and co‐workers [57] . Easily accessible 2‐aminoarylmethanols 82 reacted with 2‐substituted ethynylbenzaldehydes 83 under the optimized reaction condition of 5 mol % AgNO 3 in toluene at 80 °C for 3 h (Scheme 51).…”

Isoquinolone Synthesis via Zn(OTf)2-Catalyzed Aerobic Cyclocondensation of 2-(1-Alkynyl)-benzaldehydes with Arylamines

“…Among the different protocols for achieving this goal, the synthetic strategies starting from 2-(1-alkynyl)benzaldehydes are the most interesting due to their high atom utilization [15,21] (Scheme 1). Although the readily available 2-(1-alkynyl)benzaldehydes have been well-applied in the synthesis of benzo-fused six-membered heterocycles [27][28][29][30][31][32][33] and carbocycles [34][35][36][37][38][39], their applications for isoquinolone synthesis are very rare. As shown in Scheme 1, only two procedures have been reported to approach isoquinolones from the direct intermolecular cyclocondensation of 2-(1-alkynyl)-benzaldehydes with primary amines.…”