Pauson-Khand reaction alkene regioselectivity

The Pauson-Khand reaction (PKR) [96] consists of the synthesis of cyclopen-tenones by reaction of an alkene with a dicobalthexacarbonyl complexed alkyne (Scheme 57) and has recently emerged as one of the methods of choice for the obtainment of five-membered carbocyclic rings [97]. Its unique atom connectivity, which involves the two unsaturated carbons of the reagents and the carbon atom of a carbon monoxide ligand of cobalt usually in a regioselective manner (Scheme 57), has brought to refer to PKR as a [2 -I- 2 + 1] cycloaddition. 

Sufficient information about the reaction has been gathered to allow fairly accurate predictions of yield as well as of stereo- and regioselectivity.176177 The reaction proceeds via the formation of hexacarbonylalkyne-dicobalt complexes and is remarkably tolerant of functional groups in both the alkyne and the alkene. The intramolecular Pauson-Khand reaction is an effective way of preparing bi- and polycyclic systems, and the cyclization of 1,6-heptenyne derivatives to give bicyclo[3.3.0]oct-l-en-3-ones has been the most popular application of the Pauson-Khand reaction in natural product synthesis [Eq. (17)]. 

Cycloaddition of 7-oxanorbomadiene derivatives has been reported (Scheme 247). 5-Bromo-7-azanorbomenes undergo regioselective Pauson-Khand reaction to give (168). The bromine is lost during the reaction (Scheme 248). A-Protected alkynylamides undergo intramolecular reactions with alkenes to give 2-amidocyclopentenones (Scheme 249). 

Electronic effects on alkene regioselectivity in the Pauson-Khand reaction have also been observed. The regioselectivity observed in cycloadditions of norbomen-2-ones has been interpreted as arising from an electronic preference for attachment of the 5 C-S of the alkene to an alkyne carbon rather than cobalt in the bond-forming insertion step (equation 13). In these systems electronic and steric effects have been separated by carrying out identical reactions with the corresponding norbomen-2-ols, in which the... 

The Pauson-Khand reaction is especially useful for the intramolecular cycliza-tion of 1,6-enynes to give bicyclo[3.3.0]octenones. The intermolecular reaction has problems of regioselectivity when unsymmetrical alkynes or alkenes are used, although some substrates give especially good selectivity for various reasons. 

Acetylenes can undergo a number of thermal and transition metal promoted cycloaddition reactions. Besides the [2 + 2 + 2] cycloaddition (see Sect. 5) the reaction of acetylenes with late transition metal (so-called Fischer ) carbenes is noteworthy for the synthesis of highly and regioselectively functionalized naphthalene derivatives (Dotz reaction), while the co-cycloaddition of acetylenes with alkenes and carbon monoxide gives cyclopentenones (Pauson-Khand reaction) [159,160]. 

Schore introduced the first examples of intramolecular Pauson-Khand reaction (Scheme 2-13), resolving the regioselectivity issue observed in the intermolecular Pauson-Khand reaction. The intramolecular version employs a carbon tether, linking the alkene and alkyne moieties, leading to the formation of a bicyclic product. Since the debut of this reaction, it has been extensively used as the key step in natural product synthesis. ... 

Most Pauson-Khand reactions have been conducted with an alkene, an alk5me, and CO. However, PKRs have been developed with aUenynes (Scheme 17.36). Narasaka reported the first example of an intramolecular allenyne PKR catalyzed by an iron complex, and Brum-mond has extensively studied the allenic Pauson-Khand reaction. These reactions have been catalyzed by the combination of Mo(CO) and DMSO or by [Rh(CO)2Cl]2, and several examples are shown in Equations 17.77 and 17.78. - The reactions in Equations 17.77 and 17.78 illustrate the different regiochemistry of the products from reactions catalyzed by molybde num and rhodium. Computational studies indicate that different geometries of octahedral Mo(0), and square-planar Rh(I) species account for the different regioselectivities. ... 

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). 

Another cobalt-mediated cyclization reaction is the Pauson Khand reaction (PKR). In a [2 -H 2 - - 1] fashion, the reaction of TMSA with alkenes delivers regioselectively silylated cyclopen-tenones. Following the trend typically observed in the PKR, the bulky TMS-group is always positioned a to the carbonyl group (eqs 37 and 38)7 ... 

Pauson-Khand cyclopentenone synthesisThe cycloaddition of an alkene with an alkyne complexed with Co2(CO) usually furnishes a mixture of two cy-clopentenones when the alkene is unsymmetrical. The regioselectivity can be improved markedly if the alkene bears a heteroatom that can coordinate with the cobalt complex. Both sulfur and nitrogen ligands can improve the yield and regio-control of this reaction. 

Simple acyclic olefins are rather poor Pauson-Khand substrates under thermal conditions. Ethylene reacts moderately well with terminal but less well with internal acetylenes [98,107]. Usable reaction rates require forcing conditions which, fortunately, can be optimized for catalytic use of the metal [Eq. (46)] [108]. Substituted olefins give very variable results, but reveal interesting regiochemical aspects of the process. Cycloaddition of vinylcyclohexane with phenylacetylene proceeds to a mixture of 4- and 5-cyclohexyl-2-phenyl-2-cyclopentenones in 45% overall yield. Regioselectivity is total with respect to the acetylene, as expected. However, insertion of the alkene proceeds with little regiochemical preference. Evidently, in going from... 

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