Rh(III)-Catalyzed Enaminone-Directed Alkenyl C–H Activation for the Synthesis of Salicylaldehydes

Abstract

A Rh(III)-catalyzed enaminone-directed alkenyl C-H coupling with alkynes for the synthesis of salicylaldehyde derivatives is reported. This represents a unique example of benzene ring framework formation through a transition-metal-catalyzed, directed C-H activation strategy. The two incorporated reactive functionalities, aldehyde and hydroxy groups, provide convenient synthetic handles for further structural elaboration.

Rhodium-Catalyzed Regioselective Double Annulation of Enaminones with Propargyl Alcohols: Rapid Access to Arylnapthalene Lignan Derivatives

“…With the support of the above studies and the known literature, , a plausible mechanism is proposed in Scheme . A five-membered rhoda-cycle A was formed by C–H bond activation in 1a .…”

“…On the other hand, transition metal − catalyzed C–H activation emerged as a powerful tool to access the complex architectures in concise pathways. Among various catalysts, rhodium-based − ,, complexes proved to be highly reliable and distinctive with their remarkable features like robustness, selectivity, functional group tolerance, etc. Appropriate reactive directing functional groups lead to annulations that afford cyclic motifs in a concerted manner.…”

“…Earlier, Li and Tan et al elegantly used the α-keto sulfoxonium ylide as a traceless directing group under rhodium­(III)/cobalt­(III) catalysis in an annulation with disubstituted acetylenes (Scheme a). Later, Zhu et al discovered enaminone as a reactive/traceless DG in the C–H functionalization toward similar annulation (Scheme b). Unsymmetrical alkynes in both cases suffered from a regioselectivity issue.…”

Recent Advances in Organic Synthesis Based on N,N-Dimethyl Enaminones

“…Although to some extent the discrepancy in the deuterium-labeling experiments between Loh and Zhu's report can be explained, the differences in the C-H activation by the copper salt and the silver salt may be the main reason (Scheme 20). 22,23 Work that was very similar to that of Zhu was disclosed by Gao later in 2018, in which the Rh(III)-catalyzed regioselective [4+2] cyclization reaction of vinyl enaminones with internal alkynes was realized to synthesize sterically hindered polysubstituted salicylaldehydes (Scheme 21). 24 Moreover, the cyclization reaction exhibited a broad substrate scope and excellent functional group tolerance (e.g., p-methoxy, phenyl, naphthyl, thienyl, piperonyl).…”

“…Almost simultaneously, Zhu's group reported a similar Rh(III)-catalyzed alkenyl C(sp 2 )-H functionalization of N,Ndimethyl enaminones via coupling with alkynes to synthesize salicylaldehyde derivatives (Scheme 19). 23 The proposed mechanism of this unique transformation starts with the reaction of [RhCp*Cl 2 ] 2 /AgSbF 6 with Cu(OAc) 2 to generate the rhodium(III) acetate species Rh-I, coordination of which with the carbonyl group of 21 and C-H activation affords rhodacycle complex Rh-II. Next, ligand exchange between AcOH and the alkyne 22 yields a Rh-III intermediate.…”