Alkynes Pauson-Khand reaction

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. 

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 ... 

A combination of a metathesis and a Pauson-Khand reaction, which leads to tricyclic compounds starting from diene-ynes, has been described by Perez-Castells and colleagues [262]. Treatment of the Co-complex 6/3-86, obtained from the corresponding alkyne in 75 % yield, with 5 mol% of the Ru-catalyst 6/3-13 for 18 h, followed by addition of an N-oxide as trimethylamine-N-oxide (TMANO) or NMO as copromoters, gave 6/3-87 in 81% yield. 

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 can be facilitated by preparing the necessary ene-yne in situ by an allylic substitution of an alkyne with allylic acetate using a Pd°- and Rh-catalyst The yield of the cydization product 6/4-24 ranges from 0 % with X = O (6/4-24a) to 92% with X=NTs, as well as X = C(C02Et)2 (6/4-24c) (Scheme 6/4.8) [283],... 

It has also been found that the indolizinoquinoline iV-oxidc 291 can be used as a chiral promoter in enantioselective Pauson-Khand reactions in the reaction of norbornene with various alkynes, ee s of up to 33% were obtained in the presence of this promoter <1998H(48)1445>. 

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... 

Schore, N. E. Transition Metal Alkyne Complexes Pauson-Khand Reaction. In Comprehensive Organometallic Chemistry II Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds. Elsevier Oxford, 1995 Vol. 12, pp 703-739. 

Scheme 16.50 Remarkable effect of a (methylthio)alkyne moiety on the Pauson-Khand 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). 

Scheme 12 Ruthenium-catalyzed hetero Pauson-Khand reactions with alkynes and al-lenes...

Conversion of a Co2(CO)6-alkyne complex into a cyclopentenone is the Pauson-Khand reaction. It proceeds by loss of CO from one Co to make a 16-electron complex, coordination and insertion of the C6=C7 K bond into the C2-Co bond to make the C2-C6 bond and a C7-Co bond, migratory insertion of CO into the C7-Co bond to make the C7-C8 bond, reductive elimination of the C1-C8 bond from Co, and decomplexation of the other Co from the C1=C2 k bond. The mechanism is discussed in the text (Section B.l.f). 

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... 

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. 

Schore NE (1991) Org React 40 1 Schore NE (1991) The Pauson-Khand reaction. In Trost BM (ed) Comprehensive organic synthesis, vol 5. Pergamon Press, Oxford, p 1037 Pauson PL (1985) Tetrahedron 41 5855 Schore NE (1995) Transition metal alkyne complexes Pauson-Khand reaction. In Abel EW, Stone EGA, Wilkinson G (eds) Comprehensive organometallic chemistry II, vol 12. Pergamon Press, Oxford, p 703 Iwasawa N (1992) Chem Lett 473... 

Zhang has proposed a mechanism for the rhodium-catalyzed Alder-ene reaction based on rhodium-catalyzed [4-1-2], [5-i-2], and Pauson-Khand reactions, which invoke the initial formation of a metallacyclopentene as the key intermediate (Scheme 8.1) [21]. Initially, the rhodium(I) species coordinates to the alkyne and olefin moieties forming intermediate I. This intermediate then undergoes an oxidative cycHzation forming the metallacyclopentene II, followed by a y9-hydride elimination to give the appending olefin shown in intermediate III. Finally, intermediate III undergoes reductive elimination to afford the 1,4-diene IV. 

When this reaction is carried out under 1 atm of nitrogen or GO atmosphere, a cyclopentane 276 is formed selectively in a minute at 25 °G (Scheme 13, mode 2). Although the Pauson-Khand reaction of 1,6-enyne 273 (Scheme 13, mode 3) gives 21H, this transformation is completely suppressed under the conditions of mode 1. Even simple alkyne silylformylation product 277 is not detected at all. This contrasts sharply to the silylformylation of l-penten-4-yne 48 carried out under similar conditions (Equation (12)). These results can be explained by a pathway similar to the reaction of 1,6-diynes (i) stepwise insertion of the acetylenic and olefmic moieties into the Rh-Si bond in this order, and (ii) subsequent interaction of GO and Mc2PhSiH with the resultant intermediate to give 275. The... 

Aminocarbonylation has been combined with the Pauson-Khand reaction to construct fused tricyclic alkaloid skeletons (see 00154). The tandem aminocarbonylation/Pauson-Khand reaction of haloalkynes with a chiral allylic amine promoted by Co2(CO)8 gave angular triquinanes as exemplified in Scheme 25. Thus, the reaction of l-chloro-2-phenylethyne 175 with Co2(CO)8 at 0°C gave alkyne-dicobalt complex 176, which was converted to enoyl-dicobalt complex 177 upon warming to 25 °C. The reaction of enoyl-dicobalt complex 177 with cyclopente-nylmethyl(l-phenylethyl)amine 179 yielded Pauson-Khand reaction product, angular triquinane 180, via A -allylic aminocarbonylated alkyne-dicobalt complex 178 (Scheme 25). ... 

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]. 

Cyclobutenes, in Pauson-Khand reaction, 11, 352 Cyclocarbonylation reactions, alkynes, 10, 714 Cyclo-C3 complexes, with molybdenum carbonyls, 5, 440 Cyclo-C4 complexes, in molybdenum carbonyls, 5, 448 Cyclochrome P450cam, aryldiazene reactions, 6, 107 Cyclodextrins... 

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