Palladium(II)/Lewis Acid-Catalyzed Oxidative Olefination/Annulation of N-Methoxybenzamides: Identifying the Active Intermediates through NMR Characterizations

Abstract

Although Pd(II)-catalyzed C−H activation in arenes has been widely successful in organic synthesis with many palladacycle compounds isolated as the intermediates in liganddirected C−H activation, direct identification of the reaction intermediates such as the π-complex prior to the C−H activation is still not successful because of their instability. In the present study, we introduce a Pd(II)/LA (LA: Lewis acid)-catalyzed oxidative olefination/annulation reaction between N-methoxybenzamides and acrylates with oxygen as the oxidant source, in which two intermediates, including an unsymmetrical η 6 -complex and a palladacycle species without the proton releasing to the environment, were identified through NMR characterizations. The in situ formation of the heterobimetallic Pd(II)/LA species such as Pd(II)/Sc(III) may have enhanced the electrophilic properties of the Pd 2+ cation, thus improving the stability of the π-complex, herein, an unsymmetrical η 6 -complex, and improving its catalytic efficiency. The observed insensitive electronic effect preferred the concerted metalation−deprotonation (CMD) mechanism for this C−H activation, and the detected palladacycle intermediate without the proton releasing to the environment offered an experimental clue to support the proposed CMD mechanism.

Pd(ii)/Lewis acid catalyzed regioselective olefination of indole with dioxygen

“…6–8,28,43–46 Herein, adding Cu(OAc) 2 instead of Cu(OTf) 2 to Pd(OAc) 2 as the catalyst provided only 35% yield of 3a , much less than that (75%) obtained by adding Sc(OTf) 3 , highlighting the significant role of the Lewis acid properties of the added non-redox metal ions in this Pd( ii )/LA catalysis as well as in our previous studies. 11–19 In addition, adding HOTf instead of Sc(OTf) 3 to Pd(OAc) 2 as the catalyst gave only 11% yield of 3a , and using Pd(OTf) 2 directly as the catalyst did not provide the olefination product, however plenty of palladium black was formed (Table 1, entries 13 and 14). In the control experiments without Pd(OAc) 2 , Lewis acids such as Sc(OTf) 3 alone could not catalyze this reaction (Table 1, entry 15).…”

“…The active Pd( ii )/Sc( iii ) catalyst existed as a diacetate bridged heterobimetallic Pd( ii )/Sc( iii ) cluster, as shown in previous studies. 10–17 The linkage of the Sc 3+ cation to the Pd( ii ) species through the acetate bridge enhanced its electrophilic properties, thus improving its catalytic efficiency. Apparently, a stronger Lewis acid may provide a better enhancement of the electrophilic properties of the Pd( ii ) species, thus offering a higher promotional effect in this Pd( ii )/LA catalyzed indole olefination reaction, as shown in Table 1.…”

“…So far, this Pd( ii )/LA catalysis has been applied in olefin oxidation and isomerization, benzene hydroxylation, alkyne oxidation, nitrile hydration, the olefination/annulation of benzamides, the oxidative olefination of indole to bis(indolyl)methanes, and the decarboxylative addition of propiolic acid with indole to bis(indolyl)methanes. 10–17 Moreover, its application has also been expanded to oxidative S–P bond formation with the Ni( ii )/LA catalyst. 18 Remarkably, dioxygen was generally employed as the oxidant in these oxidation involved syntheses.…”

“…18 Remarkably, dioxygen was generally employed as the oxidant in these oxidation involved syntheses. 10,13,16,18,19 Thereof, this Pd( ii )/LA catalysis is a novel strategy in catalyst design for versatile organic syntheses with dioxygen as the sole oxidant.…”

Rhodium(III)-Catalyzed Oxidative Cyclization of Oxazolines with Cyclopropanols: Synthesis of Isoindolinones

“…Recently, direct C–H bond functionalization under transition-metal catalysis has emerged as a powerful strategy for the preparation of C3-substituted isoindolin-1-ones in a highly atom-economical and environmentally friendly manner. For instance, transition-metal-catalyzed oxidative couplings between benzamides and numerous terminal olefins followed by aza-Michael cyclization constituted a straightforward route to isoindolinone derivatives (Scheme a) . Moreover, the C3-substituted isoindolin-1-ones can be obtained via direct C–H carbonylation of protected or free benzylamines with various carbonyl sources by using Pd­(II), Ru­(II), or Co­(II) catalysis (Scheme b) .…”