Ethylene Pauson-Khand reaction

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. 

Application of the Pauson-Khand reaction to simple acylic alkenes has been limited by both low reactivity and lack of regiocontrol in incorporation of the alkene. Among simple alkenes, ethylene provides the most consistently useful results. Yields with terminal alkynes range from 30-60% (equations 9,15 and 16) internal alkynes have also been used with some success (equation 10). Forcing conditions (toluene, 130-160 C, 6()-80 atm, autoclave) are usually required for best results, although it has been recently demonstrated that the reaction proceeds, albeit slowly, at reduced pressures and temperatures (equation 17). ... 

Numerous synthetic applications of the intermolecular Pauson-Khand reaction have been reported. Pauson has reported a number of very direct applications of cycloadditions of ethylene in the synthesis of prostanoids and jasmone analogs (e.g. equations 15 and This is a reliable entry to 2-sub-... 

Considerable effort has been devoted to achieving the intermolecular catalytic Pauson-Khand reaction. The mthenium complex-catalyzed reaction of an alkyne with an alkene such as ethylene or 2-norbornene under CO gave hydroquinone derivatives [79], with CO (2 mol) being introduced into the products (Eq. 11.36). This reaction is the first example of the preparation of hydroquinone derivatives by the reaction of alkynes and alkenes with CO, while hydroquinone is synthesized by the ruthenium-catalyzed reaction of 2 mol acetylene with 2 mol CO (Eq. 11.37) [80]. 

The total synthesis of the sesquiterpene (+)-taylorione was achieved in the laboratory of J.G. Donkervoort who used the modified Pauson-Khand reaction to prepare the five-membered ring of the natural product. The preformed alkyne-cobalt complex was exposed to excess triethylamine-A/-oxide, which oxidized off two CO ligands to free up a coordination site for the ethylene. The optimum pressure of the ethylene gas had to be at 25 atm, and the reaction was conducted in an autoclave. 

Donkervoort, J. G., Gordon, A. R., Johnstone, C., Kerr, W. J., Lange, U. Development of modified Pauson-Khand reactions with ethylene and utilization in the total synthesis of (+)-taylorione. Tetrahedron 1996, 52, 7391-7420. 

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. ... 

Other reports include reactions in supercritical ethylene, promotion by molecular sieves, and the effect of a phosphine sulfide. Clusters such as methylidynetricobalt nonacarbonyl are also effective catalyst of the Pauson-Khand reaction." Vinyl esters are identified as surrogates for ethylene. ... 

Although tremendous advances in the catalytic Pauson-Khand reaction have been made, the development of an asymmetric version did not share the same degree of success. Several asymmetric Pauson-Khand reactions were reported using chiral auxiliaries. However, those systems required stoichiometric amounts of cobalt as well as the chiral source. Attempts at using a catalytic amount of cobalt did not give satisfactory results. By contrast, the use of titanium chiral catalyst S,Sy (EBTHI)Ti(CO)2 (EBTHI = ethylene-l,2-bis(tiM,5,6,7-tetrahydro-l-indenyl)... 

An intramolecular Pauson-Khand reaction of silicon-tethered enynes has been reported as an alternative method to an inter-molecular Pauson-Khand reaction with ethylene. The alkynyl vinylsilylether 51 was cyclized with Co2(CO)g in refluxing acetonitrile with 1 % H2 O to afford the cyclized enone 52 in good yield (eq 24) The final product 52 was exclusively formed without any... 

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. 

W.J. Kerr and co-workers carried out the total synthesis of (+)-taylorione starting from readily available (+)-2-carene and using a modified Pauson-Khand annulation with ethylene gas as the key step. The key terminal alkyne intermediate was prepared by the Corey-Fuchs reaction. Interestingly, the ketal protecting group was sensitive to the excess of CBr4, so the addition of this reagent had to be monitored carefully to cleanly transform the aldehyde to the desired dibromoolefin. 

Imhof, W., Anders, E., Gobel, A., Gorls, H. Atheoretical study on the complete catalytic c cle of the hetero-Pauson-Khand-type [2+2+1] cycloaddition reaction of ketimines, carbon monoxide and ethylene catalyzed by iron carbonyl complexes. Chem.— Eur. J. 2003, 9,1166-1181. 

The first report of a catalytic intermolecular cyclization was made by Pauson and Khand in 1974 [22], but the scope was limited to gaseous acetylene as the alkyne partner, strained olefins such as norbornene and norbornadiene as the alkene component, and TON s (turnover numbers) were modest (8-11). Several subsequent reports detailed the production of cyclopentenones from a substoi-chiometric amount of Co2(CO)g, but none were as efficient as Pauson s initial work [23,24]. Using ethylene as the alkene component, Rautenstrauch demonstrated the first efficient catalytic Pauson-Khand cyclization with a TON of 220, Eq. (5) [25]. A more general catalyst system employing (indenyl)Co(cod) was recently reported by Chung and Jeong, Eq. (6) [26]. The reaction was quite effec-... 

The availability of a chiral version of Cp2Ti(CO)2 was instrumental in the development of the first catalytic asymmetric Pauson-Khand type reaction [39]. This work utilized a catalyst containing the ethylene-1,2-bis( 17 -4,5,6,7-tetrahydro-l-indenyl) (EBTHI) ligand (Fig. 4,16) first introduced into Group 4 chemistry by Brintzinger [40]. Complexes containing this ligand have proven extremely effective in a number of applications in asymmetric catalysis [41]. 

Simple acyclic olefins are rather poor Pauson-Khand substrates under thermal conditions. Ethylene reacts moderately well with terminal but less well with internal acetylenes [98,107]. Usable reaction rates require forcing conditions which, fortunately, can be optimized for catalytic use of the metal [Eq. (46)] [108]. Substituted olefins give very variable results, but reveal interesting regiochemical aspects of the process. Cycloaddition of vinylcyclohexane with phenylacetylene proceeds to a mixture of 4- and 5-cyclohexyl-2-phenyl-2-cyclopentenones in 45% overall yield. Regioselectivity is total with respect to the acetylene, as expected. However, insertion of the alkene proceeds with little regiochemical preference. Evidently, in going from... 

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