Abstract:In this work, we describe a palladium-catalyzed intermolecular O acylation of α-diazoesters with ortho-bromobenzaldehydes. The C(sp )-H bond activation of the aldehyde is enabled by migratory insertion of a palladium carbene intermediate. The diazoesters act as modular three-atom units to build up key seven-membered palladacycles, which are transformed into a variety of isocoumarin derivatives upon reductive elimination. Mechanistic experiments and DFT calculations provide insight into the reaction pathway.
“…Based on the results obtained above and our previous study, a plausible catalytic cycle for current isocoumarin synthesis was depicted in Scheme . Oxidative addition of 1a could give an aryl palladium(II) intermediate I .…”
Section: Resultsmentioning
confidence: 99%
“…As an application of above mentioned carbene bridging C–H activation (CBA) strategy, we have recently realized a palladium‐catalyzed intermolecular acylation of aryl diazoesters with ortho ‐bromobenzaldehydes (Scheme d) , . In this specific reaction, a palladium carbene intermediate was produced prior to C–H bond palladation.…”
A reaction mode on carbene bridging C–H activation (CBA) is described. In this reaction, metal carbene was produced prior to the event of C–H bond metallation. Readily available aryl dizaoesters were employed as the carbene precursors. Migratory insertion of the palladium carbene intermediate could create a modular bridging arm to promote the C–H bond palladation of tethered aldehyde moiety. Its synthetic potential was demonstrated by facile construction isocoumarin scaffold from easily accessible starting materials. Furthermore, this protocol is also amenable for late‐functionalization of complex molecules.
“…Based on the results obtained above and our previous study, a plausible catalytic cycle for current isocoumarin synthesis was depicted in Scheme . Oxidative addition of 1a could give an aryl palladium(II) intermediate I .…”
Section: Resultsmentioning
confidence: 99%
“…As an application of above mentioned carbene bridging C–H activation (CBA) strategy, we have recently realized a palladium‐catalyzed intermolecular acylation of aryl diazoesters with ortho ‐bromobenzaldehydes (Scheme d) , . In this specific reaction, a palladium carbene intermediate was produced prior to C–H bond palladation.…”
A reaction mode on carbene bridging C–H activation (CBA) is described. In this reaction, metal carbene was produced prior to the event of C–H bond metallation. Readily available aryl dizaoesters were employed as the carbene precursors. Migratory insertion of the palladium carbene intermediate could create a modular bridging arm to promote the C–H bond palladation of tethered aldehyde moiety. Its synthetic potential was demonstrated by facile construction isocoumarin scaffold from easily accessible starting materials. Furthermore, this protocol is also amenable for late‐functionalization of complex molecules.
“…Then the Pd II species A reacts with the diazoacetate 4a to form Pd II carbene species B . A subsequent migratory insertion of carbene into the Pd−C bond affords π -allylpalladium species C 56 – 59 , which is followed by a hydrogen-elimination to provide the desired product 5a . Fig.…”
The rational design based on a deep understanding of the present reaction mechanism is an important, viable approach to discover new organic transformations. β-Hydrogen elimination from palladium complexes is a fundamental reaction in palladium catalysis. Normally, the eliminated β-hydrogen has to be attached to a sp3-carbon. We envision that the hydrogen elimination from sp2-carbon is possible by using thoroughly designed reaction systems, which may offer a new strategy for the preparation of allenes. Here, we describe a palladium-catalyzed cross-coupling of 2,2-diarylvinyl bromides and diazo compounds, where a β-vinylic hydrogen elimination from allylic palladium intermediate is proposed to be the key step. Both aryl diazo carbonyl compounds and N-tosylhydrazones are competent carbene precursors in this reaction. The reaction mechanism is explored by control experiments, KIE studies and DFT calculations.
“…Recently, we have reported a palladium‐catalyzed intermolecular acylation of aryl diazo esters with o ‐bromobenzaldehydes, in which diazo esters act as modular three‐atom units to build up the key seven‐membered palladacycles I (Scheme a) . To test the synthetic potential of this concept, we envisioned that replacement of carbonyl group with proper C−C double bond may give a seven‐membered carbopalladacyle II , which upon reductive elimination would afford a transient ketone III .…”
A new strategy for the construction of the naphthalene backbone is described. The reaction essentially starts from two simple aldehydes. The key step is enabled by a palladium-carbene migratory insertion. After that, a sequence of reversible allylic alkylation and intramolecular condensation takes place to give the substituted naphthalene derivatives. Additional manipulations on the sulfonyl group in the product via palladiumcatalyzed Kumada coupling were also investigated.Cascade reactions are considered as powerful methods to construct structurally complex molecules from simple and readily available feedstocks, while omitting tedious procedures to isolate synthetic intermediates, thus rendering it economic and environmentally benign. [1] Diazo compounds are easily accessible, possessing tunable reactivity. They are often employed as carbene precursors to participate in a range of classical transformations. [2] As demonstrated by the seminal work of van Vranken, Barluenga, Wang, and others, diazo compounds have also proved to be versatile in a variety of transition-metal-catalyzed cross-coupling reactions. [3,4] Recently, we have reported a palladium-catalyzed intermolecular acylation of aryl diazo esters with obromobenzaldehydes, in which diazo esters act as modular three-atom units to build up the key seven-membered palladacycles I (Scheme 1a). [5] To test the synthetic potential of this concept, we envisioned that replacement of carbonyl group with proper CÀC double bond may give a seven-membered carbopalladacyle II, which upon reductive elimination would afford a transient ketone III. Aromatization of III would lead to the formation of final product naphthalen-1-ol (Scheme 1b). In this communication, we would like to describe our efforts toward this goal which leads to an unexpected discovery of a cascade reaction of o-bromobenzaldehydes with a, b-unsaturated N-sulfonylhydrazones enabled by migratory insertion of palladium carbene. This reaction is efficient for the synthesis of a range of naphthyl sulfones and the expected naphthalen-1-ol is not observed (Scheme 1c). Naphthalene unit is an ubiquitous skeleton in chemical and pharmaceutical industries as well as optical and electronic materials. [6] Compared with the existing methods on build up the naphthalene backbone, [7] the current work uses simple aldehydes as the reactants, giving the corresponding substituted naphthalenes in complete regioselectivity with relatively broad substrates scope, thus making this strategy unique and attractive.To begin our study, we chose readily available obromobenzaldehyde 1 a and N-tosylhydrazone 2 a as model substrates. The reaction was initially carried out in DMF at 60 8C for 24 h using Pd 2 dba 3 · CHCl 3 /PPh 3 as the precatalyst, K 2 CO 3 as base (Table 1, entry 1). After careful analysis of the reaction mixture, naphthyl sulfone 3 aa was isolated in 9% yield, and the designed naphthalene-1-ol was not observed. Further inspection of the reaction conditions revealed that COMMUNICATIONS
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