Alkynes Pauson-Khand cycloadditions

Pauson-Khand Cycloaddition. Pauson Khand cycloaddition (see Pauson-Khand Reaction) is a cobalt-mediated method to prepare cyclopentenone from the cyclization of an alkyne with an alkene and CO (equation 14). This method is widely used to produce cychc ketones. Originally, stoichiometric amounts of Co2(CO)g were used in these reactions with the cobalt carbonyl being the CO source. However, it was shown that a strict temperature profile and high-purity reagents allowed the use of catalytic amounts of Co2(CO)g for reactions with 1 atm of CO. Currently, there is intense interest in developing catalytic cobalt starting materials for use in Pauson-Khand reactions. 

Co2(CO)g has been used in numerous reactions in addition to the plethora of substitution reactions that it undergoes with phosphines, nitrosyls, alkynes, and so forth. Many of these substituted carbonyl complexes and their reactions have been discussed elsewhere in this report. One area in which Co2(CO)g has received much attention is catalysis two classes of catalytic reactions of which Co2(CO)g plays a major role are hydroformylation (see Hydroformylation) and Pauson Khand cycloaddition (see Pauson-Khand Reaction). 

The reaction was first reported by Khand and Pauson et al. in 1973d It is the dicobalt octacarbonyl [Co2(CO)8l mediated or promoted one-step synthesis of a,p-unsaturated cyclopentenone from the [2+2+1] cycloaddition of alkyne, alkene and carbon monoxide, through an intermediate of alkynedicobalt hexacarbonyl complex. Therefore, this reaction is generally known as the Pauson-Khand reaction, Pauson-Khand cyclization, or Pauson-Khand cycloaddition. Occasionally, this reaction is also referred to as the Pauson-Khand annulation, Pauson-Khand multicomponent cycloaddition, Pauson-Khand carbonylative cocyclization, Pauson-Khand bicyclization, Khand annulation, Khand cycloaddition, Khand cyclization (cyclisation ), or Khand reaction.Among these names, the Pauson-Khand reaction is the one used most often. 

Two syntheses of racemic furanether B (18.8) were described by N.E. ScHORE et al. (755), (755). Both feature an octacarbonyldicobalt catalysed cycloaddition of 8-oxabicyclo 3.2.1 oct-6-ene derivatives with alkynes (Pauson-Khand reaction) as a key step. The bicyclic ketone 26.71, prepared by [4+3] cycloannulation from 2-methyfuran and tetrabromoacetone, was used as starting material. 

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. 

Co-catalyzed transformations are concerned mainly with the [2+2+2] cycloadditions of three alkyne groups to give arenes. Another important reaction is the [2+2+1] cycloaddition of alkynes, alkenes and CO to give cyclopentenones, which is the well-known as Pauson-Khand reaction [272]. 

It is not quite clear which step takes place first - the Co-catalyzed [2+2+1] cycloaddition of the outer alkyne moiety, or the Diels-Alder reaction of the diene with the inner alkyne to form a 1,4-cyclohexadiene, which then undergoes a Pauson-Khand reaction with the remaining alkyne. Recently, it has been shown that a domino reaction can also be performed using 1 mol of a 1,7-diphenyl-1,6-diyne 6/4-20 and a 1,3-diene 6/4-21 in the presence of Co/C at 150 °C under 30 atm CO, to give the polycyclic compounds 6/4-22 as sole product (Scheme 6/4.7) [282]. 

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... 

Pauson-Khand cyclopentenone synthesisThe cycloaddition of an alkene with an alkyne complexed with Co2(CO) usually furnishes a mixture of two cy-clopentenones when the alkene is unsymmetrical. The regioselectivity can be improved markedly if the alkene bears a heteroatom that can coordinate with the cobalt complex. Both sulfur and nitrogen ligands can improve the yield and regio-control of this reaction. 

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). 

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... 

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... 

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. 

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]. 

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

Nadal and colleagues recently reported a Ni-catalyzed carbonylative Pauson-Khand-like [2+2+1] cycloaddition of allyl halides and alkynes in the presence of carbon monoxide and iron as the stoichiometric reducing agent [148]. The reaction was proposed to occur via reductively generated Ni(I)-radical like species free radicals were, however, considered unlikely. 

Among the carbonylative cycloaddition reactions, the Pauson-Khand (P-K) reaction, in which an alkyne, an alkene, and carbon monoxide are condensed in a formal [2+2+1] cycloaddition to form cyclopentenones, has attracted considerable attention [3]. Significant progress in this reaction has been made in this decade. In the past, a stoichiometric amount of Co2(CO)8 was used as the source of CO. Various additive promoters, such as amines, amine N-oxides, phosphanes, ethers, and sulfides, have been developed thus far for a stoichiometric P-K reaction to proceed under milder reaction conditions. Other transition-metal carbonyl complexes, such as Fe(CO)4(acetone), W(CO)5(tetrahydrofuran), W(CO)5F, Cp2Mo2(CO)4, where Cp is cyclopentadienyl, and Mo(CO)6, are also used as the source of CO in place of Co2(CO)8. There has been significant interest in developing catalytic variants of the P-K reaction. Rautenstrauch et al. [4] reported the first catalytic P-K reaction in which alkenes are limited to reactive alkenes, such as ethylene and norbornene. Since 1994 when Jeong et al. [5] reported the first catalytic intramolecular P-K reaction, most attention has been focused on the modification of the cobalt catalytic system [3]. Recently, other transition-metal complexes, such as Ti [6], Rh [7], and Ir complexes [8], have been found to be active for intramolecular P-K reactions. 

Cycloadditions of an Alkyne, a Carbonyl Functionality, and CO Hetero-Pauson-Khand-Type Reaction... 

The metal mediated synthesis of cyclopentenones via a [2 + 2+1] cycloaddition between an alkyne, an alkene and carbon monoxide has become commonly known as the Pauson-Khand (PK) reaction. This report will briefly summarise some of the major developments since its initial discovery including an intramolecular variant of the reaction, the progress made towards making the process catalytic and examples of how the reaction has been utilised. The proposed mechanism for the reaction and the factors that influence the product distribution will also be introduced. 

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). 

This review has already indicated numerous applications of dicobalt-alkyne complexes in organic synthesis. Like the Nicholas reaction (see Section II,D), the Pauson-Khand reaction has seen widespread use.175 This reaction is a three-component cycloaddition of alkynes with alkenes and carbon monoxide which occurs in the presence of octacarbonyldicobalt to afford cyclopentenones, as shown in Eq. (16). 

When compounds (7) were heated with alkyne in excess, two types of complexes, both involving alkyne coupling, are formed. A compound with the stoichiometry Co2(CO)4(C4R2CO)2, formed mainly from terminal alkynes having one bulky substituent R, represents derivatives of Co2(CO)g where two CO groups at either metal are replaced by a cyclopentadienone ligand. This compound type represents one of the many instances where alkynes combine with CO in the presence of a transition metal fragment to yield mostly cyclopentadienones, often complexed to the metal this cycloaddition reaction is similar to the Pauson-Khand scheme except for the use of an alkyne in place on an alkene (see also Section 5.1.4 and Scheme 26). The reaction eventually proceeds further to liberate an arene. Thus, from the use of t-BuC=CH, the alkyne trimerization product 1,2,4-tri-f-Bu-benzene was isolated. 

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