Regioselectivity Pauson-Khand reaction

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. 

An important advance was reported by Schore and Croudace [13], who showed for the first time that carbon-tethered enyne precursors undergo an intramolecular Pauson-Khand reaction (PKR) in good yields with complete control of regioselectivity. In this connection, it was not essential to use strained olefins as starting materials. 

The authors stated that the steric effect of the substituent of the inner triple bond inhibits the reaction path leading to the fenestrane framework. Indeed, intermediate 40, obtained after the first Pauson-Khand reaction, displays a congested carbon-carbon double bond on the cyclopentadienone framework. This leads to a regioselective second Pauson-Khand reaction on the less hindered position (Scheme 20). 

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... 

Dihydrofiirans have seen considerable use as substrates in the Pauson-Khand reaction. The parent compound reacts in excellent yield with acetylene, terminal and internal alkynes. Yields in this system respond very well to the use of catalytic reaction conditions (equation 4). Another unusual experimental modification has also been found by Pauson to be useful in this system addition of tri-n-butylphosphine oxide nearly doubles the product yield in certain cases (equation 37). The role of the added substance is unclear. Addition of phosphine oxide does not always improve reaction efficiency at this time there are no guidelines to indicate when its use might be beneficial. Substituted dihydrofurans give somewhat lower but still acceptable yields the poor regioselectivity in unsymmetrical cases is the more significant difficulty with these substrates (equation 38). 

Derdau, V., Laschat, S., Jones, P. G. Evaluation of the regioselectivity in Pauson-Khand reactions of substituted norbornenes and diazabicyclo[2.2.1]heptanes with terminal alkynes. Eur. J. Org. Chem. 2000, 681-689. 

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. 

Intramolecular Pauson-Khand reactions are often regioselective because it is physically impossible for the molecule to cyclise any other way. Pauson-Khand disconnection of bicyclic 111 reveals an allyl ether 112 of the alcohol 113, easy to make from acetylene and cyclohexanone. In the cobalt-catalysed cyclisation, only one regioisomer is possible and this, the TM111, is formed in an excellent 80% yield.28... 

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]. 

Allenamides are functionalized at the a-position by virtue of the regioselective lithiation. Thus, on introduction of an alkynyl chain, valuable precursors of the Pauson-Khand reaction can be prepared. Lithiation of the silyl ethers of propargyl or allenyl alcohols engenders O —>C transsilylation. ... 

Continuous, selective hydroformylation in supercritical CO2 using (acac)Rh(CO)2 immobilized on silica as catalyst shows certain advantages. A version of asymmetric hydroformylation in this medium has also been reported,. (Subcritical CO2 gas accelerates solventless synthesis involving solid reactants, including hydrogenation and hydroformylation.) The regioselective and enantioselective nickel-catalyzed hydrovinylation of styrenes in supercritical CO2 make 3-arylpropenes available in an optically active form. " Improvement in the performance of the Pauson-Khand reaction in supercritical media... 

Abstract Recent density functional theory computations of cobalt-catalyzed hydroformylation of propene, A -vinyl acetamide, 1,3-butadiene, acetylene, propyne, and allene and the urea formation from methyl amine as well as Pauson-Khand reaction have been reviewed. The detailed catalytic mechanism and regioselectivity have been discussed and compared with the available experimental data. It shows that modem computational chemistry provides not only qualitative but also quantitative aspects of catalytic reactions. 

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). 

---