Serial Ligand Catalysis:  A Highly Selective Allylic C−H Oxidation

Abstract

Conventional homogeneous catalysis relies on one transition metal/ligand combination to promote all steps within a catalytic cycle. This approach is suboptimal when different steps within the cycle place different demands on the catalyst. Herein we report for the first time a serial ligand catalysis mechanism in which two different ligands interact sequentially with the metal to promote different product-forming steps of the same catalytic cycle. We recently reported sulfoxide-promoted, catalytic Pd(OAc) 2 / benzoquinone (BQ)/AcOH R-olefin allylic oxidation systems 1 that have the interesting feature of furnishing either predominantly linear or branched allylic acetates depending on whether DMSO or bissulfoxide ligands are used, respectively. 1a While investigating the bis-sulfoxide-promoted system, we discovered that 1 partially decomposes 2 under the reaction conditions to generate vinyl sulfoxide 2 (Table 1). We tested commercially available 2 and found that 10 mol % 2/Pd(OAc) 2 effectively promotes the oxidation reaction to furnish branched products with no decomposition. 1b,3 Reducing the equivalents of AcOH significantly improves regioselectivities (Table 1, entries 3a,b) by suppressing a background Pd(II)-mediated isomerization. 4 We now report a vinyl sulfoxidepromoted catalytic system for the mild, chemo-(R-versus internal olefins), and highly regioselective C-H oxidation of R-olefins to furnish allylic alkyl and aryl esters that proceeds via a mechanism in which two different ligands are responsible for promoting different steps in the catalytic cycle (Table 3). Mechanistic studies were carried out to establish the fundamental steps of this catalytic cycle and the role of vinyl sulfoxide 2 and BQ therein. When stoichiometric mixtures of 1-undecene, Pd(OAc) 2 , and 2 were heated and monitored by 1 H NMR, dimeric π-allylpalladium acetate complex A was observed in ca. 59% yield (eq 1). 5a-c When BQ was then added to this reaction mixture, formation of allylic acetate product was observed with yields and regioselectivities similar to those observed for the stoichiometric reaction run in the presence of BQ (eq 1, Table 1, entry 3h). In the absence of 2, with and without BQ, formation of complex A was not observed. These data are consistent with 2, and not BQ, acting as a ligand to effect Pd-mediated allylic C-H cleavage to likely form a monomeric π-allylpalladium intermediate that is detected in the form of dimeric complex A.

Mechanistic investigations of bipyrimidine-promoted palladium-catalyzed allylic acetoxylation of olefins

“…Furthermore, the allylic C-H activation is irreversible, because neither olefin exchange nor deuterium incorporation into the allyl fragment is observed after heating 2 with p-allyltoluene in CD 3 COOD at 80°C for 15 h (Scheme 1). Similar irreversibility was also proposed for the sulfoxide-Pd(OAc) 2 system (8).…”

“…It has been proposed that coordination of benzoquinone to Pd II induces acetate attack (8,17), but we find that the rate of the reaction between 2 and benzoquinone in acetic acid is independent of the benzoquinone concentration when at least 5.8 equiv. are used (Fig.…”

“…The solvent often plays a key role in achieving selective oxidation to allyl acetates: in neat acetic acid, only symmetrical cyclic olefins are selectively oxidized with Pd(OAc) 2 (5), whereas terminal olefins can be selectively oxidized in DMSO/acetic acid (6), and yields can be further improved in dimethylacetamide (DMA) (7). The combination of Pd(II) with sulfoxide ligands also selectively oxidizes terminal olefins (8); this reaction has been successfully applied for catalytic allylic aminations (9) and macrolactonizations (10).…”

Palladium(II)‐katalysierte C‐H‐Aktivierung/C‐C‐Kreuzkupplung: Vielseitigkeit und Anwendbarkeit

“…[58] Die in unserer Arbeitsgruppe entwickelten Pd [59] Ein kurzer Vergleich der vorgeschlagenen C-H-Aktivierung/C-C-Kupplung mit den Pd 0 -katalysierten Kreuzkupplungen [60] [61] Es war bekannt, dass Benzochinon ein Oxidationsmittel für Pd 0 ist und die C-C-Bindungsbildung in verschiedenen Pdkatalysierten Reaktionen begünstigt. [62] Unsere Untersuchungen zur Bildung von cyclopalladierten Intermediaten und ihrer Folgereaktion mit Organozinnreagentien ließen jedoch eine zusätzliche Rolle für Benzochinon erkennen: die Begünstigung der C-H-Aktivierung. Insbesondere die Tatsache, dass Benzochinon die C-C-Bindungsbildung in einer Aren-C-H-Aktivierung/Olefinierung unterstützt, [13] war für unsere Forschung überaus wichtig (Schema 6).…”

PdII‐Catalyzed Enantioselective Activation of C(sp2)H and C(sp3)H Bonds Using Monoprotected Amino Acids as Chiral Ligands

“…Benzoquinone (BQ) is required for the CÀH activation [14] and reductive-elimination steps. [15] Ag 2 O reoxidizes the Pd 0 species back to Pd II to close the catalytic cycle. The obtained triarylmethane derivatives are widely used in medicinal and material sciences.…”