Redox-Neutral Access to Isoquinolinones via Rhodium(III)-Catalyzed Annulations of O-Pivaloyl Oximes with Ketenes

Abstract

A mild and redox-neutral [4 + 2] annulation of O-pivaloyl oximes with ketenes has been realized for synthesis of quaternary-carbon-stereocenter-containing (QCSC) isoquinolinones, where the N-OPiv not only acts as an oxidizing group but also offers coordination saturation to inhibit protonolysis. The reaction mechanism has been studied by DFT calculations.

Rhodium(III)-Catalyzed C–H Activation-Based First Total Synthesis of 6-O-Methyl Anciscochine, an Alkaloid Isolated from Ancistrocladus tectorius

“…It has been suggested that the pivalate moiety may stabilize this inter-mediate and that coordination saturation of the rhodacycle also serves to inhibit protonolysis of the Rh-C alkyl bond. 29 Although different alternatives can be considered, one plausible scenario is that the metallacycle may subsequently rearrange, undergoing C-N bond formation and leading to a coordinated Rh(I) species (C) able to undergo internal oxidation with the oxime pivalate moiety as built-in oxidant to afford the Rh(III)-coordinated dihydroisoquinoline intermediate D. 26 Decomposition of D may yield a catalytically active Rh(III) species and release the 3,4-dihydroisoquinoline intermediate E, thus accomplishing a full catalytic cycle. It has been suggested that the presence of the acid additive facilitates the rhodium oxidation process.…”

Variability of Rhodium(III)-Catalyzed Reactions of Aromatic Oximes with Alkenes

“…Several groups have shown that reactions of O-acetyl oximes with dienes, 15 vinyl acetates, 16,17 vinyl aldehydes, 18 or ketones, 18 are accompanied by aromatization and give isoquinolines. Similar reactions proceed without aromatization in the case of activated alkenes such as ketenes 19 or urea-derived bicycle olefins. 20 Rovis and co-workers found that acrylate oximes are apparently more active than aromatic ones, and their O-pivaloyl derivatives can react with various alkenes with or without aromatization (Scheme 1, equation D).…”

Rh(III)-Catalyzed C–H Bond Activation for the Construction of Heterocycles with sp3-Carbon Centers

“…Assembling a heterocyclic motif with other heterocyles into polycyclic fused-heterocycles is an important tactic to discover novel biological active molecules for medicinal chemistry. In 2014, Lin's group reported two tunable arylative cyclizations of cyclohexadienone-containing 1,6-enynes with Ketenes (R 1 R 2 C=C=O) are highly reactive reagents that have been widely used in the synthesis of complex carbonyl compounds in metal-catalyzed addition and cross-coupling reactions [99]. Li's group in 2018 realized a mild and redox-neutral Rh(III)-catalyzed [4 + 2] annulation of O-pivaloyl oximes with ketenes to isoquinolin-4(3H)-ones which is also an important privileged structure in medicinal chemistry [99], in which the N-OPiv played a key role that not only acts as an oxidizing group but also offers coordination saturation to inhibit protonolysis.…”