Acetylenes Pauson-Khand reaction

In situ generation of Coi(CO)m V synthesis are related to its complexaiion by reduction of CoBr2 with Zn dust un acetylene. Pauson-Khand reactions can... 

The Pauson-Khand reaction was originally developed using strained cyclic alkenes, and gives good yields with such substrates. Alkenes with sterically demanding substituents and acyclic as well as unstrained cyclic alkenes often are less suitable substrates. An exception to this is ethylene, which reacts well. Acetylene as well as simple terminal alkynes and aryl acetylenes can be used as triple-bond component. 

An enantioselective intramolecular Pauson-Khand reaction based on chiral auxiliary-directed 7t-face discrimination in acetylenic 0-alkyl enol ether-dicobalt hexacarbonyl complexes, which proceeds with good yields and high facial diastereoselectivity, has recently been developed by M.A. Pericas, A. Moyano, A.E. Greene and their associates. The method has been applied to an enantioselective formal synthesis of hirsutene. Moreover, the process is stereodivergent and the chiral auxiliary -rran5-2-phenylcyclohexanol- is recovered in a yield as high as 92% [18]. 

In sharp contrast to the unique pattern for the incorporation of carbon monoxide into the 1,6-diyne 63, aldehyde 77 was obtained as the sole product in the rhodium-catalyzed reaction of 1,6-enyne 76 with a molar equivalent of Me2PhSiH under CO (Scheme 6.15, mode 1) [22]. This result can be explained by the stepwise insertion of the acetylenic and vinylic moieties into the Rh-Si bond, the formyl group being generated by the reductive elimination to afford 77. The fact that a formyl group can be introduced to the ole-finic moiety of 76 under mild conditions should be stressed, since enoxysilanes are isolated in the rhodium-catalyzed silylformylation of simple alkenes under forcing conditions. The 1,6-enyne 76 is used as a typical model for Pauson-Khand reactions (Scheme 6.15, mode 2) [23], whereas formation of the corresponding product was completely suppressed in the presence of a hydrosilane. The selective formation of 79 in the absence of CO (Scheme 6.15, mode 3) supports the stepwise insertion of the acetylenic and olefmic moieties in the same molecules into the Rh-Si bond. 

When this reaction is carried out under 1 atm of nitrogen or GO atmosphere, a cyclopentane 276 is formed selectively in a minute at 25 °G (Scheme 13, mode 2). Although the Pauson-Khand reaction of 1,6-enyne 273 (Scheme 13, mode 3) gives 21H, this transformation is completely suppressed under the conditions of mode 1. Even simple alkyne silylformylation product 277 is not detected at all. This contrasts sharply to the silylformylation of l-penten-4-yne 48 carried out under similar conditions (Equation (12)). These results can be explained by a pathway similar to the reaction of 1,6-diynes (i) stepwise insertion of the acetylenic and olefmic moieties into the Rh-Si bond in this order, and (ii) subsequent interaction of GO and Mc2PhSiH with the resultant intermediate to give 275. The... 

An application of the Pauson-Khand reaction for the synthesis of a carbaprostacyclin analogue (Scheme 11) [44] illustrates the power of organometallic methods for the activation of olefins and acetylenes. 

Ethynylcyclopropanes, like normal acetylenes, react with dicobalt octacarbonyl in ether to form stable dinuclear cluster-like hexacarbonyl complexes (equation 170)236. The complex with l-chIoro-2,2,3,3-tetramethylethynylcyclopropane reacts stereo- and regioselec-tively with norbomene in a typical Pauson-Khand reaction to give the exn-2-cyclopropyl substituted cyclopentenone (equation 171). Similarly, the reaction of 2-ethoxycyclo-propylacetylene with cyclopentene in the presence of Co2(CO)8 under CO gave 3-(2-ethoxycyclopropyl)-cw-bicyclo[3.3.0]oct-3-en-2-one (equation 172)242. 

Electron-deficient acetylenes, silylformylation, 11, 483 Electron-deficient substrates, Pauson—Khand reaction, 11,353 Electron-deficient unsaturated bonds boron conjugate additions, 9, 214 cycloadditions to, 9, 314... 

To explain this observation, it was suggested that electron density differences at the acetylenic carbons can combine with steric effects to determine the regiochemical outcome of the reaction. Krafft concludes electronic effects seem to play a contributing role in determining the regiochemical outcome of the Pauson-Khand reaction, but, steric influences over the transition state apparently exert a more powerful directing effect. ... 

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). 

Considerable effort has been devoted to achieving the intermolecular catalytic Pauson-Khand reaction. The mthenium complex-catalyzed reaction of an alkyne with an alkene such as ethylene or 2-norbornene under CO gave hydroquinone derivatives [79], with CO (2 mol) being introduced into the products (Eq. 11.36). This reaction is the first example of the preparation of hydroquinone derivatives by the reaction of alkynes and alkenes with CO, while hydroquinone is synthesized by the ruthenium-catalyzed reaction of 2 mol acetylene with 2 mol CO (Eq. 11.37) [80]. 

Further, replacement of the acetylenic part in the Pauson-Khand reaction by a carbonyl or imine group has been successfully achieved. a,/3-Unsaturated imines react with CO in the presence of Ru3(CO)i2 catalyst to give carbonylative [4 -i- 1] cycloadducts, y-lactams, in high yields [86], A possible mechanism is shown in Scheme 11.4. Coordination of a,/3-unsaturated imine to "Ru(CO)4 gives 9, which is converted into 10 via oxidative cyclization. Subsequent carbonylation of 10 gives 11, the reductive elimination of which gives 12 (Eq. 11.42). 

The third compound was made by a Pauson-Khand reaction using the same starting material = the first. The only difference between these two target molecules is the position of the double bor. In the Nazarov reaction, it goes into the thermodynamically most favourable position but in 1-Pauson-Khand reaction it goes where the alkyne was. So we simply react the cyclic ether wci acetylene cobalt carbonyl complex. The cis stereochemistry is inevitable. 

Castro, J., Moyano, A., Pericas, M. A., Riera, A., Alvarez-Larena, A., Piniella, J. F. Acetylene-Dicobaltcarbonyl Complexes with Chiral Phosphinooxazoline Ligands Synthesis, Structural Characterization, and Application to Enantioselective Intermolecular Pauson-Khand Reactions. J. Am. Chem. Soc. 2000,122, 7944-7952. 

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... 

Ester-based chiral auxiliaries have also beat used in other settings. P-Alk-oxyesters 1.27 of (R)-1 -phenylethanol 1.1 (R = Me, Ar = Ph) or (5)-1-naphthyl-ethanol 1.1 (R = Me, Ar = 1-Np) are transformed into dural synthons by reactions with a lithiated carbanion a to phosphorous followed by hydrogenolysis [194], Ethers 1.28 of chiral alcohols 1.1 undergo selective alkylations or hydroxyalkyla-tions [169]. The auxiliaries can be removed by hydrogenolysis. Enol or dienol ethers 1.29 and 1 JO suffer [2+2] [195, 196] or [4+2] cycloadditions [49, 197,198, 199], The best stereoselectivities are obtained when the chiral auxiliary is 1.1 (R = r-Pr, Ar=Ph), 1.4 (R=Ph), 1.5 (R = Ph), 1.10 or 1.13. These auxiliaries are cleaved either by acid treatment [199] or by other means in subsequent steps. Acetylene ethers G OC=CR derived from 1.5 (R=Ph) [199a] can undergo stereoselective Pauson-Khand reactions [200, 201], The auxiliaries are removed by treatment of the products with Sml2 in THF-MeOH. 

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]. 

The alkyne-Co2(CO)6 complexes 1 are the binuclear cluster complexes of the acetylenic derivatives with the hexacarbonyldicobalt moiety. These complexes can be readily prepared by treatment of alkynes with commercially available octacarbonyldicobalt [Co2(CO)g] and can regenerate the parent triple bond functionality under some mild oxidation conditions. Two synthetically very useful reactions have so far been developed by taking advantage of the characteristic properties of the alkyne-Co2(CO)6 complexes 1 one is so-called Nicholas reaction" and the other is so-called Pauson-Khand reaction (Scheme 1). The alkyne-Co2(CO)6 complexes 1 possessing a hydroxyl group or its equivalent at carbon p- to alkyne moiety (propargyl alcohol derivatives) could easily... 

The Pauson-Khand Reaction Cycloadditions of Olefins, Acetylenes, and CO... 

Virtually any acetylene may be successfully employed in an intermolecular Pauson-Khand reaction, although special solvents or promoters are sometimes necessary (e. g., cycloadditions of conjugated alkynones must be carried out in CH3CN [95]). 

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