Pauson-Khand-type cyclization

There has been significant interest in the development of a catalytic asymmetric Pauson-Khand type reaction because of its vast potential in organic synthesis. A boom in research activity in this field has focused in two areas - the development of catalytic Pauson-Khand type cyclizations and of stoichiometric syntheses of optically active cyclopentenones via the Pauson-Khand reaction, including a recent report of the first intramolecular catalytic asymmetric Pauson-Khand type cyclization. In this review, the existing catalytic systems will be briefly surveyed followed by a detailed analysis of the asymmetric variant. The stoichiometric syntheses of optically active cyclopentenones will also be discussed. 

Another important development in the area of catalytic Pauson-Khand type cy-clizations has been the discovery of other transition metal carbonyl complexes which are capable of effecting the catalytic synthesis of cyclopentenones. Two recent reports from Murai and Mitsudo detailed a Ru3(CO)i2-catalyzed enyne cyclocarbonylation, Eqs. (10) and (11) [34,35]. While this protocol allowed for the cyclization of a variety of l,6-enynes,the cyclizations of terminal alkynes as well as 1,7-enynes were problematic. The feasibility of using Cp2Ti(CO)2 as a catalyst for the intramolecular Pauson-Khand type cyclization of a variety of 1,6-and 1,7-enynes (vide infra) has also been demonstrated [36]. Based on the wide array of transition metals that are capable of effecting stoichiometric Pauson-Khand type cyclizations (vide supra), the development of more catalytic systems is to be expected this should greatly facilitate the search for catalytic asymmetric variants. 

In the course of studying the stoichiometric, carbonylative synthesis of y-buty-rolactones from enones and a titanocene complex [37], it was observed that certain aryl enones could be cyclocarbonylated in a catalytic manner, Eq. (12) [38]. This success in effecting a titanocene-catalyzed cyclocarbonylation led to an examination of the analogous reaction with enyne substrates. Indeed, it was found that under similar conditions, a titanocene-catalyzed Pauson-Khand type cyclization was possible, Eq. (13) [36]. 

Fig. 4. Asymmetric catalyst for the Pauson-Khand type cyclization...

A final conceptually unique approach to the asymmetric Pauson-Khand type cyclization involved the use of chiral amine oxide promoters. Kerr has reported... 

Pauson-Khand-type reactions of enynes are mediated by other metal complexes, such as Fe(CO)5 [100], [W(CO)5THF] and Mo(CO)6 [101]. Cyclization of the allene-yne system 227 to the a-methylenecyclopentenone 228 is promoted by Mo(CO)6. The products depend on the substituents of the allene, and the cyclization of 229 afforded 230 as the main product [102]. 

Intramolecular allene alkyne cyclizations using cobalt complexes are nonspecific and both double bonds of the allene participate in the reaction affording [4.3.0] and [3.3.0]ring systems (Scheme 260). Both inter- and intramolecnlar Pauson - Khand-type reactions have been reported using... 

Bicyclic cyclopentenones. Cyclization of the Pauson-Khand type from enynes is achievable with Ni(cod)j (12 examples, 38-85%). A bulky bis-ketimine ligand and a CO equivalent are present in the reaction medium. For the latter (i-Pr)3SiCN is adequate. The silyl cyanide is in equilibrium with the isocyanide. The primary products are the cyclopentenone imines, which undergo hydrolysis on workup. 

After the intense use of concerted reactions for natural product synthesis, the related metal-catalyzed cyclizations gained ground in the 1980s and 1990s. Several authors demonstrated the effectiveness of these reaction types for the synthesis of dendrobine (82). Takano et al. and Zard et al. used the Pauson-Khand reaction as a key step for their EPC-synthesis efforts (144,165,166). Mori et al. relied on the more stable zirkonacycle in a related key step (167-169), while Trost et al. employed a palladium-catalyzed alkylation as well as a palladium-catalyzed ene reaction as key steps (170). Takano s efforts ended with the tricyclic skeleton of dendrobine, whereas Mori and Trost finished their formal EPC-syntheses with intermediates of Kende s and Roush s racemic S3mtheses, respectively. Both completed dendrobine synthesis would have necessitated more than 20 steps. 

Methods for the synthesis of central hydroisoquinolines or pyrrolo-hydroisoquinoHnes of manzamine A can be classified into 11 types of reactions (1) intermolecular Diels-Alder reaction, (2) intramolecular Diels-Alder reaction, (3) photochemical reaction, (4) radical reaction, (5) ionic cyclization, (6) intramolecular Michael reaction, (7) intramolecular Maimich reaction, (8) intramolecular [3 + 2] cycloaddition, (9) intermolecular [3 + 2] cycloaddition, (10) Pauson-Khand reaction, and (11) eneyne metathesis. 

Another type of cyclization reaction, known as the Pauson-Khand reaction, involves the catalytic cocyclization of alkynes with alkenes and carbon monoxide... 

---