Ligand-Accelerated C−H Activation Reactions: Evidence for a Switch of Mechanism

Abstract

Initial rate studies have revealed dramatic acceleration in aerobic Pd(II)-catalyzed C–H olefination reactions of phenylacetic acids when mono-N-protected amino acids are used as ligands. In light of these findings, systematic ligand tuning was undertaken, which has resulted in drastic improvements in substrate scope, reaction rate, and catalyst turnover. We present evidence from intermolecular competition studies and kinetic isotope effect experiments that implies that the observed rate increases are a result of acceleration in the C–H cleavage step. Furthermore, these studies suggest that the origin of this phenomenon is a change in the mechanism of C–H cleavage from electrophilic palladation to proton abstraction.

Palladium-Catalyzed Double C–H Functionalization of Arenes at the Positions <i>ortho</i> and <i>meta</i> to Their Directing Group: Concise Synthesis of Benzocyclobutenes

“…Further screening revealed that the addition of a catalytic amount of N-9-fluorenylmethoxycarbonyl (Fmoc)-protected amino acid (20 mol%) led to a dramatic increase in the conversion of 1a to the desired product 3aa. This result was consistent with the results reported by Yu for a related reaction, 34) with valine providing the best result of all of the amino acids tested in the current study (Table 2, entries 5-9). The nature of the protecting group on the nitrogen atom of the amino acid was also found to be very important.…”

“…Although the use of a formyl or acetyl (Ac) group did not lead to an improvement in the conversion of 1a (Table 2, entries 10, 11), the use of a carbamate protecting group such as a t-butyloxycarbonyl (Boc), methoxycarbonyl or (−)-menthyloxycarbonyl (Men) group led to an increase in the conversion (Table 2, entries [12][13][14]. In contrast to previous reports from the literature, 34) the use of a smaller charge of (−)-Men-Val-OH (5 mol%) led to an increase in the conversion of 1a (Table 2, entry 15). After fine tuning the conditions for this reaction, we established that the use of 2.0 eq of Ag 2 CO 3 with 1.5 eq of BQ led to the complete conversion of 1a, with benzocyclobutene 3aa being isolated in 84% yield after silica gel column chromatography ( Table 2, entry 16).…”

“…The results of our screening experiments showed that the protected amino acid ligand was essential for this step. 34) The subsequent insertion of norbornene (2) into the resulting intermediate, followed by the meta C-H activation of the benzene ring would afford the key palladacycle from Catellani's ortho C-H functionalization mechanism. Reductive elimination from the palladacycle, which is assumed to be a rate-determining step in this transformation, would give the desired benzocyclobutene product 3 along with a Pd(0) species, which would be re-oxidized to Pd(II) by the oxidant.…”

Redox-Induced Aromatic C–H Bond Functionalization in Metal Complex Catalysis from the Electrochemical Point of View

“…However, in these cases, the mechanism should include Pd(0)/Pd(II) reoxidation of the catalyst, but not high-valent palladium intermediates [89][90][91]. However, as can be seen from the diagram in Figure 1, the oxidative strength of oxygen may not be enough to oxidize Pd(0) under certain conditions (the potential ranges of Pd(0) oxidation and O 2 reduction overlap insignificantly, at about −0.5 V).…”

Wenn C‐H‐Bindungen sprechen könnten – selektive Oxidationen von C‐H‐Bindungen

“…[81] In diesem Beispiel wurde ohne Liganden nahezu keine Selektivität beobachtet; eine erste mechanistische Untersuchung sowie eine Optimierung der ursprünglichen Bedingungen wurden kürzlich veröffentlicht. [82] Darüber hinaus sind auch viele schöne Beispiele zur Aktivierung von C(sp 2 )-H-und C(sp 3 )-H-Bindungen in heterocyclischen Substraten bekannt. Zu diesem Thema ist vor kurzem ein Übersichtsartikel erschienen.…”