Pauson-Khand reaction synthetic utility

The DOtz reaction was traditionally carried out in ethereal solvents for many years more recently solvents of low coordinating ability have been found to be superior in most situations, with yields in excess of 80<7o available from annulation of simple alkynes to arylcarbenes in hexane [13]. In fact, it has become increasingly clear that manipulation of reaction conditions, including solvent, temperature, and concentration, can be used in a synthetically useful way to drastically alter product distributions (see Sections 5.2.2 and 5.2.3). Additionally, dry-state adsorption techniques, which have expanded the utility of the Pauson-Khand reaction (see Section 5.3.3), show promise for increased reaction rates and yields in the D6tz reaction [14]. 

Pauson-Khand reaction (PKR) first reported in 1973 is formally a cobalt-mediated [2-I-2-I-1] cycloaddition involving an alkene, an alkyne, and carbon monoxide to form a cyclopentenone (145,146). The synthetic utility of the PKR was initially limited due to the poor regioselectivity observed in the intermolec-ular reaction when unsymmetrical alkynes and alkenes are used. However, the inherent regiocontrol of the intramolecular variant of the PKR has considerably expanded the synthetic utility of the reaction (147). A variety of transition metals have been shown to catalyze the PK reaction including Rh, Ti Zr, Ir, and Ru (148,149). 

Magnus was the first to develop extensive synthetic applications of the Pauson-Khand preparation of the bicyclo[3.3.0]oct-l-en-3-one system. His efforts amply demonstrate the degree to which the high level of functionality in the Pauson-Khand products can be directly utilized in building more complex structures. A formal synthesis of the antitumor sesquiterpene coriolin illustrates a very efficient sequence for construction of the third ring in the linearly fused triquinane series in the presence of considerable functionality (Schemes 10 and 18). A synthesis of the related triquinane hirsutic acid utilizes the observation that the proper stereochemical relationship between the substituents at C-7 and the ring-fusion carbon (C-5) of the bicyclo[3.3.0]oct-l-en-3-one system, while not controllable in the cycloaddition reaction itself, may be readily established by acid- or base-catalyzed equilibration (equation 54 and Scheme 19). ... 

---