Non-redox metal ion promoted oxidative coupling of indoles with olefins by the palladium(ii) acetate catalyst through dioxygen activation: experimental results with DFT calculations

Abstract

Developing new catalytic technologies through C-H bond activation to synthesize versatile pharmaceuticals has attracted much attention in recent decades. This work introduces a new strategy in catalyst design for Pd(ii)-catalyzed C-H bond activation in which non-redox metal ions serving as Lewis acids play significant roles. In the oxidative coupling of indoles with olefins using dioxygen, it was found that Pd(OAc)2 alone as the catalyst is very sluggish at ambient temperature which provided a low yield of the olefination product, whereas adding non-redox metal ions to Pd(OAc)2 substantially improves its catalytic efficiency. In particular, it provided bis(indolyl)methane derivatives as the dominant product, a category of pharmacological molecules which could not be synthesized by Pd(ii)-catalyzed oxidative coupling previously. Detailed investigations revealed that the reaction proceeds by heterobimetallic Pd(ii)/Sc(iii)-catalyzed oxidative coupling of an indole with an olefin followed by Sc(iii)-catalyzed addition with a second indole molecule. DFT calculations disclosed that the formation of heterobimetallic Pd(ii)/Sc(iii) species substantially decreases the C-H bond activation energy barrier, and shifts the rate determining step from C-H bond activation of indole to the olefination step. This non-redox metal ion promoted Pd(ii)-catalyzed C-H bond activation may offer a new opportunity for catalyst design in organic synthesis, which has not been fully recognized yet.

Transformation of Methyl Linoleate to its Conjugated Derivatives with Simple Pd(OAc)2/Lewis Acid Catalyst

“…However, when the ratio continuously increased from 1 to 2, the efficiency improvement is relatively minor. This phenomenon is similar to those in allylbenzene isomerization, but distinctly different from that in Wacker-type oxidations catalyzed by Pd(OAc) 2 /Lewis acid [33][34][35]. In Wacker-type oxidation, the Sc(III)/Pd(II) ratio of 4 is much more efficient than the ratio of 1.…”

“…Inspired by these findings, we explored non-redox metal ions as Lewis acid-promoted olefin isomerization and its oxidative coupling with indoles by a Pd(OAc) 2 catalyst. In those reactions, the role of Lewis acid is assigned to improve the C-H bond activation ability of the Pd(II) cation through the formation of heterometallic Pd(II)/Lewis acid (LA) species, and related DFT calculations have supported this assignment [34,35]. Here, we report an example of such a simple Pd(OAc) 2 /LA system in biomass utilization, that is, catalyzing isomerization of methyl linoleate to its corresponding conjugated derivatives, whereas Pd(OAc) 2 alone is inactive.…”

Regioselective Direct C‐Alkenylation of Indoles

“…Formation of these bisindoles can be practically suppressed adding AcOH to the reactionmixture. [29] As previously stated, 3-alkenylindoles can be used as dienes in Diels-Alder reactions and this methodc an be exploited for the regioselective synthesis of 1,3-symmetrical carbazoles starting from indoles and a,b-unsaturated carbonyl derivatives (Scheme 7). [30] The alkenylations tep has been demonstrated to be catalyzed by Pd and Cu salts and requiresalarge excess of alkenes for an efficient reaction.…”

“…In this reaction a variable amount of bisindolyl derivatives arising from a Friedel–Crafts reaction of the target 3‐indolyl acrylates with the indole substrates are often observed. Formation of these bisindoles can be practically suppressed adding AcOH to the reaction mixture …”

A General Strategy for Open‐Flask Alkene Isomerization by Ruthenium Hydride Complexes with Non‐Redox Metal Salts

“…Evidenced by mechanism studies, the presence of non‐redox metal ions can change the coordination structure of reactive species substantially, which regulates their catalytic activities –. The presence of non‐redox metals may also alter the reaction pathway and control the yield distribution of different oxidative products . Particularly in the case of Ru catalysts, we found that the addition of non‐redox metal ions as Lewis acids can accelerate the catalytic epoxidation of olefins and saturated C−C bond dehydrogenation .…”