Pauson-Khand cyclopentenone synthesis

Formal [2 + 2 +1] cycloaddition of an alkene, alkyne, and carbon monoxide mediated by octacarbonyl dicobalt. 

Pauson, P. L. Watts, W. E. J. Chem. Soc., Chem. Commun. 1971, 36. Ihsan U. Khand and Peter L. Pauson were at the University of Strathclyde, Glasgow in Scotland. 

Schore, N. E. In Comprehensive Organic Synthesis, Paquette, L. A. Eleming, 1. Trost, B. M., Eds. Pergamon Oxford, 1991, Vol. 5, p.l037. (Review). 

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Other synthetic reactions. Catalyzed elimination of allylic carbonates occurs in the absence of nucleophiles. Alkynediols undergo isomerization and dehydration, furnishing 2,5-disubstituted furans as a result. 1-Carboranyltributyltin adds to aldehydes under the influence of the Pd catalyst to form carbinols. The Pd version of a Pauson-Khand cyclopentenone synthesis is accomplishable in the presence of CO, and actually this version is specially suited for a one-step construction of a -methylenecyclopentenones. ... 

Alkyne(hexacarbonyl)dicobalt complexes containing cyclopropanes have been used as building blocks in Pauson Khand type synthesis of cyclopentenones. These results are compiled in several reviews on the application of the Pauson-Khand methodology, describing use of... 

Alkyne- Co2(CO)6) complexes for application in the Pauson-JChand cyclopentenone synthesis have been prepared in simple and convenient fashion by reduction of cobalt bromide by zinc in the presence of alkynes under carbon monoxide. An intramolecular Pauson-Khand reaction has been used 172 to incorporate the proper stereochemistry at the C/D/E rings of Xestobergsterol D. The use of Co2(CO)6l-alkyne complexes as stable intermediates for the construction of the core structures of the anti-tumor enediyne agents esperamicin, calicbeamicin, dynemicin and neocarzinostatin has been reviewe(H73,... 

KHAND PAUSON Cyclopentenone Annulat/on Cyclopentenone synthesis from cartxin monoxide acetylene and olefins, cobalt carbonyl catalyzed. 

The Pauson-Khand reaction is the Co-induced formation of cyclopentenones from ene-ynes and CO. One impressive example of a domino Pauson-Khand process is the synthesis of fenestrane 6/4-15, as reported by Keese and colleagues [278]. The transformation is initiated by a double Grignard reaction of 4-pentynoic acid 6/4-12, followed by protection of the formed tertiary hydroxyl group to give 6/4-13. The Co-induced polycyclization of 6/4-13 led directly to the fenestrane 6/4-15... 

In a similar manner, Brummond et al. demonstrated the first total synthesis of 15-deoxy-A12,14-prostaglandin J2 (162) that was completed using a silicon-tethered allenic Pauson-Khand reaction to obtain the highly unsaturated cyclopentenone substructure [36]. Treatment of alkynylallene 160 with molybdenum hexacarbonyl and dimethyl sulfoxide affords the desired cycloadduct 161 in 43% yield (Scheme 19.30). Trienone 161 was obtained as a 2 1 Z E mixture of isomers in which the Z-isomer could be isomerized to the desired E-isomer. The silicon tether was cleaved and the resulting product converted to 15-deoxy-A12,14-prostaglandin J2 (162). 

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). 

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. 

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... 

Passerini Reaction, 65, 1 Pauson-Khand reaction to prepare cyclopentenones, 40, 1 Payne rearrangement, 60, 1 Pechmann reaction, 7, 1 Peptides, synthesis of, 3, 5 12, 4 Peracids, epoxidation and hydroxylation with, 7, 7... 

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]. 

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

Interestingly, zirconacyclopentane 246 formed by the reaction of 1,6-heptadiene with the Zr complex has the firms ring junction mainly [108]. It should be noted that the preparation of the trans ring junction in the bicyclo[3.3.0]octane system by other means is difficult. Carbonylation of 246 affords trans-fuzed bicyclo[3.3.0]octanone 247 [109,111]. The diacetoxy compound 248 is obtained by oxidative cleavage of 246. Protonation affords the frans-dimethylcyclopentane skeleton. Similar reactions occur with 1,6-enynes, and Pauson Khand-type cyclopentenone synthesis is possible by carbonylation. 

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. 

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). 

The Pauson-Khand Cycloaddition Reaction for Synthesis of Cyclopentenones... 

Cyclopropene can also be used as the aUcene component and affords bicyclo[3.1.0]hexen-2-ones upon reaction with alkyne dicobalt octacarbonyl complexes in the presence of NMO (Scheme 250). Vinyl ethers and vinyl esters serve as ethene equivalents in Pauson-Khand reactions. For example, reaction of vinyl benzoate with complex (169) furnished cyclopentenone (170) (Scheme 251). This reaction was used in a synthesis of (-l-)-taylorine and nortaylorine. Allenes participate in intermolecular Pauson-Khand reactions affording alkylidene-substituted cyclopentenones (Scheme 252). ... 

Revision of Chapter 36. What would be the starting materials for the synthesis of these cyclopentenones by the Nazarov reaction and by the Pauson-Khand reaction Which do you prefer in each case - ... 

Schore, N. E. The Pauson-Khand cycloaddition reaction for synthesis of cyclopentenones. Org. React. 1991,40, 1-90. 

Pauson-Khand reactions. This salt Na[CpMo(CO)3] converts alkyne-dicobalthexacarbonyl complexes into mixed Co-Mo analogs which often show higher reactivities in the cyclopentenone synthesis. 

The Pauson-Khand reaction is a powerful tool for the synthesis of cyclopentanones, 246, from a>-alkenylacetylenes, 245, and carbon monoxide.176 Enyne cyclization has been catalyzed with nitriles using catalytic (77S-CsH5)2Ti(PMe3)2 95177-179 and other variants have since been discovered where the desired cyclopentenones can be directly prepared from the enyne and CO using (77S-CsHs)2Ti(CO)2 68 (Scheme 33) 176,180-184 Addition of PMe3 to the latter reaction mixture has proved to be beneficial. Stoichiometric reactions established that the initial step in the catalytic cycle is reductive coupling of the alkyne and the olefin to form the titanacycle. Carbon monoxide insertion followed by reductive elimination generates the observed product. 

Numerous synthetic applications of the inteimolecular Pauson-Khand reaction have been reported. Pauson has reported a number of very direct tqrplications of cycloadditions of ethylene in the synthesis of prostanoids and jasmone analogs (e.g. equations 15 and 16). - This is a reliable entry to 2-sub-stituted cyclopentenones. The suitability of cyclopentene and dihydrofuran as substrates has permitted the extension of this work to the preparation of still further varieties of prostaglandin analogs (e.g. equations 27 and 51). Simple 4,5-disubstituted 2-cyclopentenones are not as directly accessible, but may be prepared from the cycloaddition products of norbomadiene (equation 45). A sequence of conjugate addition followed by retro-Diels-Alder reaction affords the product (Scheme 5). Dihydrofuran cycloadditions have been used by Billington in the syntheses of the antibiotic methylenomycin B (Scheme 6), as well as cyclomethylenomycin A (synthetic precursor to the antibiotic methylenomycin A), cyclosarko-mycin (precursor to the antitumor agent sarkomycin) ° and the iridoid Jq>anese hop ether. ... 

In chapter 6 we described the use of the remarkable Pauson-Khand reaction for the synthesis of cyclopentenones. If the components (CO, alkene and alkyne) are tethered by a nitrogen atom, a heterocycle will also be formed. The first stage in this process is to couple the cobalt carbonyl complex, e.g. 236, of ahalo-alkyne with an amine containing the alkene in the side chain. The best way to do this is to react 234 with Co2(CO)9 to give 235 and then 236 and to capture this complex with the amine without isolation of intermediates.34... 

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