Carbon Pauson-Khand reaction

The reaction of an alkyne 1 and an alkene 2 in the presence of dicobaltoctacar-bonyl to yield a cyclopentenone 3 is referred to as the Pauson-Khand reaction Formally it is a [2 + 2 + 1 ]-cycloaddition reaction. The dicobaltoctacarbonyl acts as coordinating agent as well as a source of carbon monoxide. 

The reaction of alkenes with alkenes or alkynes does not always produce an aromatic ring. An important variation of this reaction reacts dienes, diynes, or en-ynes with transition metals to form organometallic coordination complexes. In the presence of carbon monoxide, cyclopentenone derivatives are formed in what is known as the Pauson-Khand reaction The reaction involves (1) formation of a hexacarbonyldicobalt-alkyne complex and (2) decomposition of the complex in the presence of an alkene. A typical example Rhodium and tungsten ... 

The Pauson-Khand reaction (PKR) [96] consists of the synthesis of cyclopen-tenones by reaction of an alkene with a dicobalthexacarbonyl complexed alkyne (Scheme 57) and has recently emerged as one of the methods of choice for the obtainment of five-membered carbocyclic rings [97]. Its unique atom connectivity, which involves the two unsaturated carbons of the reagents and the carbon atom of a carbon monoxide ligand of cobalt usually in a regioselective manner (Scheme 57), has brought to refer to PKR as a [2 -I- 2 + 1] cycloaddition. 

The [2+2+1] cycloaddition of an alkene, an alkyne, and carbon monoxide is known as the Pauson-Khand reaction and is often the method of choice for the preparation of complex cyclopentenones [155]. Groth and coworkers have demonstrated that Pauson-Khand reactions can be carried out very efficiently under microwave heating conditions (Scheme 6.75 a) [156]. Taking advantage of sealed-vessel technology, 20 mol% of dicobalt octacarbonyl was found to be sufficient to drive all of the studied Pauson-Khand reactions to completion, without the need for additional carbon monoxide. The carefully optimized reaction conditions utilized 1.2 equivalents of... 

Another interesting domino Pauson-Khand reaction was presented by Cook et al. generating six carbon-carbon bonds in a one-pot process in the synthesis of dicydopenta[a,elpentalene derivatives.1801... 

Abstract The transition metal mediated conversion of alkynes, alkenes, and carbon monoxide in a formal [2 + 2+1] cycloaddition process, commonly known as the Pauson-Khand reaction (PKR), is an elegant method for the construction of cyclopentenone scaffolds. During the last decade, significant improvements have been achieved in this area. For instance, catalytic PKR variants are nowadays possible with different metal sources. In addition, new asymmetric approaches were established and the reaction has been applied as a key step in various total syntheses. Recent work has also focused on the development of CO-free conditions, incorporating transfer carbonylation reactions. This review attempts to cover the most important developments in this area. 

An important procedure for the synthesis of cyclopentenones is the so-called Pauson-Khand reaction, which constitutes a formal [2 + 2 + 1] cycloaddition of an alkene, an alkyne, and carbon monoxide. Due to the increase in structural diversity of the available starting materials, the reaction has become an attractive target for scientific investigations [1-8]. The first successful example was reported by Pauson, Khand et al [9] in 1973 for the conversion of norbornene with the phenylacetylene-hexacarbonyldicobalt complex to give the corresponding cyclopentenone in 45% yield (Eq. 1). 

An important advance was reported by Schore and Croudace [13], who showed for the first time that carbon-tethered enyne precursors undergo an intramolecular Pauson-Khand reaction (PKR) in good yields with complete control of regioselectivity. In this connection, it was not essential to use strained olefins as starting materials. 

Recent developments have impressively enlarged the scope of Pauson-Khand reactions. Besides the elaboration of strategies for the enantioselective synthesis of cyclopentenones, it is often possible to perform PKR efficiently with a catalytic amount of a late transition metal complex. In general, different transition metal sources, e.g., Co, Rh, Ir, and Ti, can be applied in these reactions. Actual achievements demonstrate the possibility of replacing external carbon monoxide by transfer carbonylations. This procedure will surely encourage synthetic chemists to use the potential of the PKR more often in organic synthesis. However, apart from academic research, industrial applications of this methodology are still awaited. 

Also alkynylcarbene complexes can react as Michael acceptors with nucleophiles, forming 1,3-dien-l-ylcarbene complexes (Figure 2.17). Both carbon nucleophiles, such as, e.g., enamines [246-249], and non-carbon nucleophiles, such as imidates [250], amines [64,131,251], aliphatic alcohols [48,79,252], phenols [252], and thiols [252] can add to the C-C triple bond of alkynylcarbene complexes. Further reactions of the C-C triple bond of alkynylcarbene complexes include 1,3-dipolar [253,254], Diels-Alder [64,234,238,255-258] and [2 -i- 2] cycloadditions [259 -261], intramolecular Pauson-Khand reactions [43,262], and C-metallation of ethynylcarbene complexes [263]. 

Khand and Pauson reported a Co-mediated intermolecular [2-I-2-I-1] cycloaddition of an alkyne, an alkene and carbon monoxide (the Pauson-Khand reaction) [4, 26] wherein an alkyne-Co2(CO)6 complex, which had been prepared from Co2(CO)g... 

The asymmetric reactions discussed in this chapter may be divided into three different types of reaction, as (1) hydrometallation of olefins followed by the C—C bond formation, (2) two C C bond formations on a formally divalent carbon atom, and (3) nucleophilic addition of cyanide or isocyanide anion to a carbonyl or its analogs (Scheme 4.1). For reaction type 1, here described are hydrocarbonyla-tion represented by hydroformylation and hydrocyanation. As for type 2, Pauson-Khand reaction and olefin/CO copolymerization are mentioned. Several nucleophilic additions to aldehydes and imines (or iminiums) are described as type 3. 

Transition-metal-promoted cycloaddition is of much interest as a powerful tool for synthesis of carbocyclic stmcture in a single step. Utilization of carbon monoxide as a component of the cycloaddition reaction is now widely known as the Pauson-Khand reaction, which results in cyclopentenone formation starting from an alkyne, an alkene, and carbon monoxide mediated by cobalt catalyst. Although mechanistic understanding is limited, a commonly accepted mechanism is shown in Scheme 4.16. Formation of dicobalt-alkyne complex followed by alkene... 

In sharp contrast to the unique pattern for the incorporation of carbon monoxide into the 1,6-diyne 63, aldehyde 77 was obtained as the sole product in the rhodium-catalyzed reaction of 1,6-enyne 76 with a molar equivalent of Me2PhSiH under CO (Scheme 6.15, mode 1) [22]. This result can be explained by the stepwise insertion of the acetylenic and vinylic moieties into the Rh-Si bond, the formyl group being generated by the reductive elimination to afford 77. The fact that a formyl group can be introduced to the ole-finic moiety of 76 under mild conditions should be stressed, since enoxysilanes are isolated in the rhodium-catalyzed silylformylation of simple alkenes under forcing conditions. The 1,6-enyne 76 is used as a typical model for Pauson-Khand reactions (Scheme 6.15, mode 2) [23], whereas formation of the corresponding product was completely suppressed in the presence of a hydrosilane. The selective formation of 79 in the absence of CO (Scheme 6.15, mode 3) supports the stepwise insertion of the acetylenic and olefmic moieties in the same molecules into the Rh-Si bond. 

The [2+2+1] cycloaddition of an alkene, an alkyne and carbon monoxide is commonly known as the Pauson-Khand reaction. This transformation has been adopted many times in the synthesis of complex natural products and related compounds, which contain a cyclopentenone moiety, for example, prostaglandins. Two independent reports of this reaction appeared almost simultaneously in late 2002 by Iqbal and co-workers25 and Fisher and co-workers26, respectively. They not only used very similar substrate systems in their studies, but they also reached very similar conclusions Toluene was found to be the preferred solvent in this reaction, even though it is a very poor microwave absorber. A reaction time between 5 and 10 min, using dicob alto ctacar-bonyl or dicobalthexacarbonyl as the carbon monoxide source, and a temperature of 100-120°C resulted in high yields of the products. Fisher and co-workers used 20 mol% Co2(CO)8 and cyclohexylamine as an additive (Scheme 5.12), since this system had been used previously in order to allow a catalytic reaction. Iqbal and co-workers did not use cyclohexylamine, but instead used 1 equiv. of the carbon monoxide (Co2(CO)6) source. In both reports, the products were formed in 40-70% yield. 

One of the earliest enantioselective carbon-carbon bond-forming processes catalyzed by chiral transition-metal complexes is asymmetric cyclopropanation discussed in Chapter 5, which can proceed via face-selective carbometallation of carbene-metal complexes. Some other more recently developed enantioselective carbon-carbon bond forming reactions, such as Pd-catalyzed enantioselective alkene-CO copolymerization (Chapter 7) and Pd-catalyzed enantioselective alkene cyclization (Chapter 8.7), are thought to involve face-selective carbometallation of acy 1-Pd and carbon-Pd bonds, respectively (Scheme 4.4). Similarly, the asymmetric Pauson-Khand reaction catalyzed by chiral Co complexes most likely involves face-selective cyclic carbometallation of chiral alkyne-Co complexes (Chapter 8,7). 

The iron-mediated [2 + 2 + 1]-cycloaddition to cyclopentadienones has been successfully applied to the synthesis of corannulene [24] and the yohimbane alkaloid ( )-demethoxycarbonyldihydrogambirtannine [25]. A [2 + 2 + l]-cydoaddition of an alkene, an alkyne and carbon monoxide mediated by pentacarbonyliron, related to the well-known Pauson-Khand reaction [26], has also been described to afford cyclopentenones [27]. 

Synthesis of Cyclopentenones by the Reaction of Alkyne, Alkene and Carbon Monoxide (Pauson-Khand Reaction)... 

The Pauson-Khand Reaction is a [2+2+1] cycloaddition of an alkyne, an alkene and carbon monoxide. 

When enyne cycloisomerization takes place in the presence of an unsaturated molecule an insertion reaction can occur. Thus, Ru3(CO)12 catalyzes the cycloisomerization of 1,6-enynes under a CO atmosphere to give an insertion of carbon monoxide and the formation of bicyclic cyclopentenones as a catalytic Pauson-Khand reaction [78] (Eq. 57). 

Some of the most exciting reactions in organic chemistry are based on transition metals. How about these two for example The first is the Heck reaction, which allows nucleophilic addition to an unactivated alkene. Catalytic palladium (Pd) is needed to make the reaction go. The second, the Pauson-Khand reaction, is a special method of making five-membered rings from three components an alkene, an alkyne, and carbon monoxide (CO). It requires cobalt (Co). Neither of these reactions is possible without the metal. 

We have concentrated on palladium because it is the most important of the transition metals but we must not leave you with the idea that it is the only one. We shall end with two reactions unique to cobalt—the Pauson-Khand reaction that we mentioned right at the start of the chapter and the Vollhardt co-trimerization. You will sec at once that cobalt has a special affinity with alkynes and with carbon monoxide. 

To explain this observation, it was suggested that electron density differences at the acetylenic carbons can combine with steric effects to determine the regiochemical outcome of the reaction. Krafft concludes electronic effects seem to play a contributing role in determining the regiochemical outcome of the Pauson-Khand reaction, but, steric influences over the transition state apparently exert a more powerful directing effect. ... 

The Pauson-Khand reaction (PKR) is among the most powerful transformations in terms of molecular complexity increment [1]. Only a few of other reactions like the Diels-Alder, or the cyclotrimerization of alkynes can compete with the PKR, which consists formally of a [2 + 2 + 1] cycloaddition in which a triple bond, a double bond and carbon monoxide form a cy-clopentenone [2-12], This constitutes one of the best ways to construct cyclopentenones, which upon further transformations can be converted into structures present in numerous natural products (Scheme 1). 

In terms of functional group compatibility, ethers, alcohols, tertiary amines, acetals, esters, amides and heterocycles are compatible with the Pauson-Khand reaction. In the intramolecular version, relatively few carbon skeletons undergo the cyclization. Most intramolecular PKRs use systems derived from hept-l-en-6-yne (6) or propargyl allyl ethers (7) or amines (8). Other interesting and more recent substrates are enynes connected through aromatic rings like 9-11, which have allowed us and other groups to obtain aromatic polycycles (Fig. 1) [28-31]. 

Martin et al. disclosed that [Rh(CO)2Cl]2 catalyzes highly regio- and stereoselective allylic alkylation using a-substituted sodiomalonates. The new C - C bond was formed at the carbon bearing the leaving group [22]. Owing to the known ability of Rh(I) complexes to catalyze carbocyclizations such as the Pauson-Khand reaction (PKR) [23,24] or [5 + 2] cycloadditions [25], Martin anticipated that the aforementioned reaction could be the first step of... 

This tandem reaction is believed to proceed via Pauson-Khand reaction between the diyne and carbon monoxide to give an intermediate bicyclopen-tadienone. 

Fenestranes are compounds of theoretical interest in which the central carbon atom undergoes severe planarization distortion. Reactions sequences involving double intramolecular Pauson-Khand reactions of ene-diynes, or intramolecular Pauson-Khand of dienynes followed by photochemical [2 + 2] cycloaddition, successfully lead to [5.5.5.5]- or [4.5.5.5]fenestrane, respectively [42], For instance, compound 37 was obtained from ene-diyne 36 in moderate yield as a single all-czs stereoisomer [43] (Scheme 18). 

The authors stated that the steric effect of the substituent of the inner triple bond inhibits the reaction path leading to the fenestrane framework. Indeed, intermediate 40, obtained after the first Pauson-Khand reaction, displays a congested carbon-carbon double bond on the cyclopentadienone framework. This leads to a regioselective second Pauson-Khand reaction on the less hindered position (Scheme 20). 

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