Alkenes 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 Pauson-Khand reaction was originally developed using strained cyclic alkenes, and gives good yields with such substrates. Alkenes with sterically demanding substituents and acyclic as well as unstrained cyclic alkenes often are less suitable substrates. An exception to this is ethylene, which reacts well. Acetylene as well as simple terminal alkynes and aryl acetylenes can be used as triple-bond component. 

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 ... 

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]. 

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... 

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). 

The Pauson-Khand reaction involves the aimulation of an alkene, an alkyne and carhon monoxide to yield cyclopentenones. Recently, it was shown that in this respect polymer-hound species (60) is an effective catalyst which may be generated by heating Co2(CO)g with polystyrene-bound phosphine (Scheme 4.37) [129]. 

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... 

As dibromocyclopropanes can easily be synthesized by reacting a cycloalkene with bromoform in the presence of a base [16], this method affords an alternative procedure for cyclopentenone annelation onto cyclic alkenes. It should be noted that in the Pauson-Khand reaction, which is probably the most direct cyclopentenone annelation reaction, the reaction using cyclohexene gives the product only in very low yield [11,17]. Also, the position of the original alkynyl substituent on the product double bond is opposite to that in the present reaction. Thus the two reactions are complementary. 

Several reports have appeared on the effect of additives on the Pauson-Khand reaction employing an alkyne-Co2(CO)6 complex. For example, addition of phosphine oxide improves the yields of cyclopentenones 119], while addition of dimethyl sulfoxide accelerates the reaction considerably [20]. Furthermore, it has been reported that the Pauson-Khand reaction proceeds even at room temperature when a tertiary amine M-oxide, such as trimethylamine M-oxide or N-methylmorpholine M-oxide, is added to the alkyne-Co2(CO)6 complex in the presence of alkenes [21]. These results suggest that in the Pauson-Khand reaction generation of coordinatively unsaturated cobalt species by the attack of oxides on the carbonyl ligand of the alkyne-Co2(CO)6 complex [22] is the key step. With this knowledge in mind, we examined further the effect of various other additives on the reaction to obtain information on the mechanism of this rearrangement. 

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]. 

Dicobalt octacarbonyl, in Pauson—Khand reaction homogeneous catalysis, 11, 340 metal-coupled promoters, 11, 339 non-oxidative promoter-assisted, 11, 338 oxidative promoter-assisted, 11, 337 physical promoters, 11, 339 solid-supported promoters, 11, 339 Dicobalt triple-decker sandwiches, preparation, 3, 14 (+)-Dictamnol, via [5+2]-cycloadditions, 10, 613-614 Dicyclohexylborane, for alkene hydroboration, 9, 150... 

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. 

The Pauson-Khand reaction, promoted by (CO)3Mo(DMF)3, has been found to take place under very mild conditions in the absence of any promoter. High yields of the adducts were obtained in the cyclization of a wide variety of functionalized 1,6- and 1,7-enynes. Enynes bearing electron-withdrawing groups at the alkene terminus proved to be particularly good substrates.121 The exclusive formation of cyclopentenones was observed in the molybdenum hexacarbonyl (10 mol%)-catalysed Pauson-Khand reactions of 1,6-allenynes under 1 atm of CO (balloon) in excellent yields.122... 

Alkyne-alkene carbonylative coupling. Intramolecular carbonylative coupling of dialkynes catalyzed by Fe(CO)3 provides a route to cyclopentadienones (equation I). The more difficult carbonylative alkyne-alkene coupling to provide cyclopen-tenones (Pauson-Khand reaction) can also be effected with Fe(CO)s, but in modest yield. In an improved coupling, acetone is treated with Fe2(CO)9 to form Fe-... 

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. 

The Pauson-Khand reaction starts with the replacement of two CO molecules, one from each Co atom, with the alkyne to form a double a complex with two C-Co a bonds, again one to each Co atom. One CO molecule is then replaced by the alkene and this n complex in its turn gives a a complex with one C-Co a bond and one new C-C a bond, and a C-Co bond is sacrificed in a ligand coupling reaction. Then a carbonyl insertion follows and reductive elimination gives the product, initially as a cobalt complex. 

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