Rhodium(III)-Catalyzed Cascade Reactions of Imines/Imidates with 4-Hydroxy-2-alkynoates to Synthesize Regioselective Furanone-Fused Isoquinoline Scaffolds

Abstract

A regioselective synthesis of furanone-fused isoquinoline heterocycles is developed in a single step using a Rh(III) catalyst. In this reaction, a cascade C−H activation, regioselective annulation, and lactonization occur in one pot. A wide range of alkynoates was examined, which showed good regioselectivity. The regioselectivity was guided by steric bulk at the C4 position of the 4-hydroxy-2-alkynoates. The synthetic utility was exemplified, and the model reaction was scaled up to a 1 g scale.

Synthetic Routes to Imidates and Their Applications in Organic Transformation: Recent Progress

“…Prabhu and his group reported the synthesis of furanone‐fused isoquinolines 149 via a cascade Rh‐catalyzed cyclization/lactonization, starting from benzimidates 147 or imines and 4‐hydroxy‐2‐alkynoates 148 [70] . Regarding the use of imidates, the desired products 149 emerged in poor yields, as opposed to the imines where good to excellent reaction yields were observed (Scheme 40b).…”

Ortho‐Functionalization of Benzimidates and Benzamidines

“…Very recently, in 2021, K. R. Prabhu and research group [43] in their work reported Rhodium (III) catalyzed cascade reaction for the synthesis of fused Isoquinoline derivatives ( 114 ) from benzimidate ( 112 ) and various 4‐Hydroxy‐2‐alkynoates ( 113 ). Ethyl benzimidate and dimethyl‐substituted 4‐hydroxy‐2‐alkynoates when stirred for 16 h at 120 °C in presence of 5 mol % of [Cp * RhCl 2 ] 2 , 20 mol% of AgSbF 6 , 2.2 equivalent of Cu(OAc) 2 .…”

“…[25] In 2011, Ihara and co-workers reported the annulation of imidates (42) with dimethyl acetylenedicarboxylate ( 44 49) in moderate to good yields (Scheme 20). [26] Based on different controlled experiments, it was revealed that cyclic imidates (imino ether) (42) were isomerized to enaminoethers (43) and attacked to alkene systems to yield the Micheal adducts. The adducts then isomerized to enamino ethers followed by cyclization by eliminating methanol as the by-product.…”

Organometallic Reagents: Efficient Tools for the Synthesis of Fused Pyridinyl‐Lactones

“…[7] Lately, a regioselective synthesis of furanonefused isoquinoline was developed using Rh III catalyst involving a one pot sequence of CÀ H activation, regioselective annulation and lactonization (Scheme 1D). [8] Obviously, it appears that a straightforward strategy allowing a general access to various 3-or 3,3-disubstituted pyridinyllactones is not available yet. Thus, in this context, we report herein our investigation on the synthesis of 3-substituted or 3,3-disubstituted pyridinyl-lactones, based on the condensation of the organometallic ethylnicotinate intermediate on carbonyl derivatives and the subsequent lactonization.…”

“…More recently furo[3,4‐ b ]quinolinones were synthesized from 2‐(1‐ethoxyalkoxy)‐3‐cyanoquinolines via sequential removal of acetal protection and intramolecular cyclization/hydration (Scheme 1C) [7] . Lately, a regioselective synthesis of furanone‐fused isoquinoline was developed using Rh III catalyst involving a one pot sequence of C−H activation, regioselective annulation and lactonization (Scheme 1D) [8] …”