Molybdenum. Pauson-Khand

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). 

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... 

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... 

Other examples of microwave-assisted catalysis include allylic alkylation, both palladium catalyzed and molybdenum catalyzed. In the latter case, air stable precursor complexes could be used under non-inert conditions. Microwave-enhanced Pauson-Khand reactions have also been reported, as have hydroamination of alkynes, and metathesis of functionalized alkynes. " Recently, microwave enhancement has been applied to C-H activation reactions, for example, for the formation of functionalized heterocycles, allowing the reaction to be performed with no solvent purification and minimal precautions to exclude air. A solvent-free chelation-assisted hydroacylation... 

This reaction has found its way into organic synthesis fi and is attractive because of its generality and selectivity. In Drummond s synthesis of hydroxymethylacylfulvene,3 0 for example, a Pauson-Khand reaction of the allene-alkyne 446 gave a 69% yield of 447. In this case, molybdenum hexacarbonyl was used. In Takano s synthesis of dendrobine, 448 was treated with dicobalt octacarbonyl and then NMO to give an 89%... 

Molybdenum hexacarbonyl. 13,194-195 15,212-213 16,225-226 18,243-244 Cyclopentenones. The Pauson-Khand reaction catalyzed by Mo(CO) in DMSO has been extended to the preparation of a-methylenecyclopentenones. 

Perez-Castells and colleagues used Co fCOlj to transform N-(2-ethynylphenyl)-N-(prop-l-enyl) acetamide to a cyclopenta[(t]indol-2-one (Scheme 2, equation 1) [7]. Saito and colleagues adapted a Pauson-Khand reaction, using either COj(CO)g or Mo(CO), to the syntheses of IH-pyrrolo[2,3-fc]indol-2-ones and 2//-thieno[2,3-( ]indol-2-ones (equation 2) [8, 9]. Molybdenum is actually superior to cobalt in these Pauson-Khand reactions vide infra). Mukai and coworkers used a cobalt Pauson-Khand reaction to synthesize pyrrolo[2,3-b]indoles including the alkaloid physostigmine (equation 3) [10,11]. 

Complexes of other transition metals have been reported to catalyze Pauson-Khand reactions. Buchwald reported intramolecular PKRs with 1.2 atm of CO at 90 °C in the presence of CpjTi(CO)2. " However, most other catalytic Pauson-Khand reactions have been conducted with late transition metal catalysts. Murai and Mitsudo simultaneously reported intramolecular PKRs catalyzed by ruthenium carbonyl clusters in dioxane or DMAc at 140-160 °C under 10-15 atm of CO. The first Rli-catalyzed PKR was reported by Narasaka. ° In this case, the reaction occurred with acceptable rates, even with CO pressures less than 1 atm. Shibata reported PKRs in refluxing xylenes under 1 atm of CO in the presence of catalytic amounts of PPli and [Ir(COD)Cl]2. Adrio and Carretero showed that the solvated molybdenum carbonyl complex Mo(DMF)3(CO)3 catalyzed intramolecular PKRs with monosubstituted olefins, as well as with disubstituted electron-poor olefins, and Hoye showed that W(CO)5(THF) catalyzes intramolecular PKRs. Iron and palladium complexes have also been reported to catalyze the PKR. 

A problem is that the Pauson-Khand reaction uses two equivalents of cobalt. More efficient versions, many of them catalytic, using other metals have been developed. These include carbonyl complexes of titanium, molybdenum, tungsten (Scheme 7.15), rhodium and ruthenium (Scheme 7.16). Rhodium, iridium and iron (Scheme 7.17) have also been used with two alkynes to give cyclopentadienones, often as complexes 7.59. A version of the Pauson-Khand reaction employing a nickel catalyst and an isonitrile in place of CO has been developed. The product is an imine, which can be hydrolysed to a cyclopentenone. 

The alkene component of the Pauson-Khand reaction can be replaced by a carbonyl group, leading to the formation of butenolides. This reaction has proved useful in butenolide synthesis using molybdenum complexes with labile ligands. It was used in a short synthesis of an epimer of dihydrocanadensolide 7.76 from aldehyde 7.74 (Scheme 7.21). It was also used in a short synthesis of mintlactone 7.79 from citronellol 7.77 (Scheme 7.22). In an interesting transformation, citronellol 7.77 was de-methylated to the alkynol, which was oxidized to the aldehyde 7.78. Carbonylation of the aldehyde 7.78 was achieved using an activated molybdenum carbonyl species. Another synthesis of mintlactone may be found in scheme 4.43. 

J. Adrio, J.C. Carretero, Butenohde synthesis by molybdenum-mediated hetero-pauson-khand reaction of alkynyl aldehydes, J. Am. Chem. Soc. 129 (2007) 778-779. 

Adrio J, Rivero MR, Carretero JC. Mild and efficient molybdenum-mediated Pauson-Khand-type reaction. Org. Lett. 

Cyclopentenone Synthesis. Synthesis of cyclopentenones from alkynes + alkenes+CO has become a widely used process and is variously known as the Khand reaction or the Pauson-Khand reaction. Although inter alia examples promoted by Pentacarbonyliron, Hexacarbonylmolybdenum, tetracar-bonylbis(cyclopentadienyl)ditungsten or -molybdenum, and car-bene(pentacarbonyl)chromium have been described, octacar-bonyldicobalt is the generally used reactant. The method has been extensively reviewed. ... 

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