Pauson domino

One of the best methods to synthesize cyclopentenone derivatives is the Pauson-Khand procedure. However, Shindo s group have recently developed a domino process consisting of a [2+2] cycloaddition of a ketone with anynolate, followed by a Dieckmann condensation to give a 3-lactone as 4-190 which is decarboxylated under reflux in toluene in the presence of silica gel to afford cyclopentenones [64a]. Thus, the reaction of 4-188 and 4-189 led to 4-190, which on heating furnished the linear cucumin 4-191 (Scheme 4.41). This natural product has been isolated from the mycelial cultures of the agaric Macrocystidia cucumis [65, 66]. The domino procedure described was also used to synthesize dihydrojasmone and a-cuparenone. Moreover, the [2+2] cycloaddition can be combined with a Michael reaction [64b]. 

Scheme 6/3.25. Domino metathesis/Pauson-Khand reaction.

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... 

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]. 

Scheme 6/4.6. Domino Pauson-Khand/Diels-Alder reaction.

A combination of Co-mediated amino-carbonylation and a Pauson-Khand reaction was described by Pericas and colleagues [286], with the formation of five new bonds in a single operation. Reaction of l-chloro-2-phenylacetylene 6/4-34 and dicobalt octacarbonyl gave the two cobalt complexes 6/4-36 and 6/4-37 via 6/4-35, which were treated with an amine 6/4-38. The final products of this domino process are azadi- and azatriquinanes 6/4-40 with 6/4-39 as an intermediate, which can also be isolated and separately transformed into 6/4-40 (Scheme 6/4.11). 

In recent years, many novel MCRs - including Michael addition-initiated three-component domino sequences [10], Knoevenagel/hetero-Diels-Alder-based MCRs [11], radical chain MCRs [12], transition metal-catalyzed Pauson-Khand MCRs [13], as well as Petasis MCRs [14], have been added to the chemisf s armamentarium and successfully applied to all fields of organic synthesis. 

A domino Pauson-Khand-Reaction was developed by Keese et al. starting from enediyne 155 leading to the shortest synthesis of a fenestrane 157 (scheme 31).1791... 

Another interesting domino Pauson-Khand reaction was presented by Cook et al. generating six carbon-carbon bonds in a one-pot process in the synthesis of dicydopenta[a,elpentalene derivatives.1801... 

Scheme 31. Synthesis of fenestranes by domino Pauson-Khand reaction...

Finally, sequential Pauson-Khand reactions (domino reactions) are possible [36, 37]. A particular fascinating application of this concept is the synthesis of a fenestrane by Keese and coworkers (Scheme 13) [36],... 

Scheme 13. Synthesis of a fenestrane by domino Pauson-Khand reaction according to Keese.

One pot synthesis of tricyclic enone 158 is possible via domino Pd-catalyzed allylation and Co-catalyzed Pauson-Khand reaction. Allylation of the propargylic malonate 156 with 3-acetoxycyclopentene under CO pressure afforded the fused tricyelic compovmd 158 via 157 in 73 % yield. Bimetallic catalyst PCNS (Pd and Co nanoparticles immobilized on silica) was used as a catalyst [55]. 

Domino reactions have attracted significant attention given that this methodology enables multistep synthesis to be completed in one pot. The early work done by Jeong et al. used a dual-catalyst system for the preparation of bicyclopentenone 339. A palladium complex was used to catalyze the allylic substitution of 556 to form the enyne intermediate 338. Subsequent Rh-catalyzed Pauson-Khand reaction furnished the desired product 339 in high yield (Scheme 2-91). ... 

Scheme 2-91. Reductive domino allylic substitution and Pauson-Khand reaction.

---