Modified Pauson-Khand reaction

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. 

Increasing reactivity in the Pauson-Khand reaction. The PK reaction originally suffered from a lack of substrate scope and low reaction yields which prevented it from being widely employed. The discovery of new reaction conditions (additives and modified methods) led to an improvement in yields and reaction times, allowing the scope of the reaction to be expanded. 

Scheme 7. A diastereoselective Pauson-Khand reaction using a chiral-modified substrate according to M. A. Pericas.

Enantioselectivities up to 44 % were reached in intermolecular PKRs when chiral aminoxides R 3N—>0 were used [19]. Although the mechanism is not known, it seems likely that the chiral A-oxide discriminates between the prochiral carbonyl cobalt units, either oxidizing one carbon monoxide selectively to produce a vacant site for the alkene insertion, or stabilizing a vacant site on one of the cobalts preferentially. This approach was modified by application of chiral precursor substrates [20]. Albeit the synthesis of the latter is cumbersome, the concept was successfully applied in several total syntheses, for example of hirsutene [21], brefeldine A [22], /9-cuparenone [23], and (+)-15-norpentalenene [24] (eq. (10)). Stoichiometric amounts of the mediator compound Co2(CO)8 are still necessary in this useful version of the Pauson-Khand reaction. 

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. 

The hnker is stable to a great variety of reaction conditions. In the example illustrated in Scheme 46, the alkynes are loaded indirectly onto the phosphine-modified polymer as their hexacarbonyldicobalt(O) complexes, but they can also be attached to a Co-coated polymer. Instead of traceless release of the alkynes after modification, they can also be apphed to Pauson-Khand reactions to form cyclo-pentenones [119]. 

For the Pauson-Khand [2+2+1] cycloaddition175 of alkyne, alkene, and carbon monoxide, as well as being promoted by Co2(CO)8, Portnoy et al.176 synthesized a dendronized support modified with 2- and 4-(diphenylphosphino)benzoic acid groups Co2(CO)8 was then incorporated into the support. A notable increase in catalytic activity and selectivity for the intramolecular Pauson-Khand reaction was found for the Co complexes immobilized on the second-and third-generation dendron-functionalized polystyrene, when compared with the analogous nondendronized support. 

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