Mechanism of the Pauson-Khand reaction

The mechanism of the Pauson-Khand reaction has not been fully elucidated. However, based on the regio- and stereochemical outcome in a large number of examples, a reasonable hypothesis has been inferred. 

The currently accepted mechanism of the Pauson-Khand reaction mediated by cobalt carbonyl systems was proposed by Magnus. This mechanism is summarized in Scheme 17.39. The reaction is initiated by irreversible replacement of CO from the starting... 

Werz DB, Schulte JH, Rausch BJ, Gleiter R, Rominger F (2004) Structural properties of bis (hexacarbonyidicobalt) complexes with heteroatoms next to the former triple bonds - a contribution to the mechanism of the Pauson-Khand reaction. Eur J Inorg Chem 2585... 

Reaction and will be reviewed below. The second mechanism is the first stage of the Doetz reaction, while the third (operating with alkynes) is the first stage of the Vollhardt reaction and of the Pauson-Khand Reaction ... 

Enantioselectivities up to 44 % were reached in intermolecular PKRs when chiral aminoxides R 3N—>0 were used [19]. Although the mechanism is not known, it seems likely that the chiral A-oxide discriminates between the prochiral carbonyl cobalt units, either oxidizing one carbon monoxide selectively to produce a vacant site for the alkene insertion, or stabilizing a vacant site on one of the cobalts preferentially. This approach was modified by application of chiral precursor substrates [20]. Albeit the synthesis of the latter is cumbersome, the concept was successfully applied in several total syntheses, for example of hirsutene [21], brefeldine A [22], /9-cuparenone [23], and (+)-15-norpentalenene [24] (eq. (10)). Stoichiometric amounts of the mediator compound Co2(CO)8 are still necessary in this useful version of the Pauson-Khand reaction. 

Pericas, M. A., Balsells, J., Castro, J., Marchueta, I., Moyano, A., Riera, A., Vazquez, J., Verdaguer, X. Toward the understanding of the mechanism and enantioselectivity of the Pauson-Khand reaction. Theoretical and experimental studies. PureAppl. Chem. 2002, 74, 167-174. 

Conversion of a Co2(CO)6-alkyne complex into a cyclopentenone is the Pauson-Khand reaction. It proceeds by loss of CO from one Co to make a 16-electron complex, coordination and insertion of the C6=C7 K bond into the C2-Co bond to make the C2-C6 bond and a C7-Co bond, migratory insertion of CO into the C7-Co bond to make the C7-C8 bond, reductive elimination of the C1-C8 bond from Co, and decomplexation of the other Co from the C1=C2 k bond. The mechanism is discussed in the text (Section B.l.f). 

Transition-metal-promoted cycloaddition is of much interest as a powerful tool for synthesis of carbocyclic stmcture in a single step. Utilization of carbon monoxide as a component of the cycloaddition reaction is now widely known as the Pauson-Khand reaction, which results in cyclopentenone formation starting from an alkyne, an alkene, and carbon monoxide mediated by cobalt catalyst. Although mechanistic understanding is limited, a commonly accepted mechanism is shown in Scheme 4.16. Formation of dicobalt-alkyne complex followed by alkene... 

Several reports have appeared on the effect of additives on the Pauson-Khand reaction employing an alkyne-Co2(CO)6 complex. For example, addition of phosphine oxide improves the yields of cyclopentenones 119], while addition of dimethyl sulfoxide accelerates the reaction considerably [20]. Furthermore, it has been reported that the Pauson-Khand reaction proceeds even at room temperature when a tertiary amine M-oxide, such as trimethylamine M-oxide or N-methylmorpholine M-oxide, is added to the alkyne-Co2(CO)6 complex in the presence of alkenes [21]. These results suggest that in the Pauson-Khand reaction generation of coordinatively unsaturated cobalt species by the attack of oxides on the carbonyl ligand of the alkyne-Co2(CO)6 complex [22] is the key step. With this knowledge in mind, we examined further the effect of various other additives on the reaction to obtain information on the mechanism of this rearrangement. 

Formation of the tricyclo[3.3.0.0.]decane 209 by the reaction of [3.2.0]bicyclo-heptadiene 205 with propyne complex (206) is an example [81], The Pauson Khand reaction is explained by the following simplified mechanism. At first the oxidative cyclization of 205 and 206 generates the cobaltacyclopentene 207, to which insertion of CO gives 208. Finally, reductive elimination of208 affords the cyclopentenone 209. 

Metallacycles have been claimed to play pivotal roles in many transition metal-mediated multi-component coupling reactions [1]. For example, [2 -i- 2 -i- 2] alkyne cyclo-trimerization leading to benzenes - the Reppe reaction - has been considered to proceed via metallacyclopentadiene and elusive metallacycloheptatriene intermediates ("common mechanism ), while metallacyclopentenes have been proposed as intermediates for the [2 -i- 2 -i- 1] cyclo-coupling reactions of an alkyne, an alkene, and CO leading to a cyclopentenone (the Pauson-Khand reaction). A metallacyclic compound - which is defined here as a carbocyclic system with one atom replaced by a transition metal element - can be generally formed by oxidative cyclization of two unsaturated molecules with a low-valent transition metal fragment [2-4]. Alter-... 

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). 

Some very widely used organic reactions are catalyzed or mediated by transition metals. For example, catalytic hydrogenation of alkenes, dihydroxylation of alkenes, and the Pauson-Khand reaction require Pd, Os, and Co complexes, respectively. The d orbitals of the transition metals allow the metals to undergo all sorts of reactions that have no equivalents among main-group elements. This doesn t mean that the mechanisms of transition-metal-mediated reactions are difficult to understand. In fact, in some ways they are easier to understand than standard organic reactions. A transition-metal-catalyzed or -mediated reaction is identified by the presence of a transition metal in the reaction mixture. 

The Pauson-Khand reaction gives the same product as the group 4 metal-mediated reductive coupling and carbonylation, and both reactions proceed by essentially the same mechanism formation of an alkyne-metal tt complex, insertion of an alkene, insertion of CO, and reductive elimination. Some details differ, however. When an alkyne is added to Co2(CO)g, CO evolves, and an isolable, chromatographable alkyne-Co2(CO)6 complex is obtained. This butterfly complex contains four Co(II)-C bonds, and the Co-Co bond is retained. The formation of the alky n e-C o2 (C O) 6 complex involves the formation of an ordinary tt complex of the alkyne with one Co(0) center, with displacement of CO. The tt complex can be written in its Co(II) cobaltacyclopropene resonance structure. The tt bond of the cobaltacyclopropene is then used to form a tt complex to the other Co center with displacement of another equivalent of CO. This second tt complex can also be written in its cobaltacyclopropene resonance structure. The alkyne-Co2(CO)6 complex has two 18-electron Co(II) centers. 

To date, the most commonly used transition metal-promoted cycloaddition in organic synthesis is the Pauson-Khand reaction. First reported by Pauson and Khandin 1973 [9],this transformation is the cobalt-mediated [2+2+1] cycloaddition of an alkyne, an alkene and carbon monoxide to form a cyclopentenone, Eq. (1). Although mechanistic understanding is Hmited, the accepted mechanism for the transformation is depicted in Fig. 2. Loss of two equivalents of CO followed by complexation of an alkyne produces 1. Subsequent loss of CO from... 

An interesting cyclization reaction was reported that involved the reaction of dienes, diynes, or ene-ynes with transition metals to form cyclopentenone derivatives in the presence of carbon monoxide.363 in a simple example, ene-yne 444 was heated with dicobalt octacarbonyl and CO to give a 68% yield of 445.364 jjjj transformation has become an important synthetic tool known as the Pauson-Khand reaction.365 jhe mechanism probably involves insertion of the alkene (or alkyne) into the transition metal bond, which is why it is presented in this section. Formally, it is a [2+2+l]-cycloaddition, but the accepted mechanism is the one proposed by Magnus,364 and shown in Figure 13.8.366 n has been stated that further study is required to... 

Zhang has proposed a mechanism for the rhodium-catalyzed Alder-ene reaction based on rhodium-catalyzed [4-1-2], [5-i-2], and Pauson-Khand reactions, which invoke the initial formation of a metallacyclopentene as the key intermediate (Scheme 8.1) [21]. Initially, the rhodium(I) species coordinates to the alkyne and olefin moieties forming intermediate I. This intermediate then undergoes an oxidative cycHzation forming the metallacyclopentene II, followed by a y9-hydride elimination to give the appending olefin shown in intermediate III. Finally, intermediate III undergoes reductive elimination to afford the 1,4-diene IV. 

The metal mediated synthesis of cyclopentenones via a [2 + 2+1] cycloaddition between an alkyne, an alkene and carbon monoxide has become commonly known as the Pauson-Khand (PK) reaction. This report will briefly summarise some of the major developments since its initial discovery including an intramolecular variant of the reaction, the progress made towards making the process catalytic and examples of how the reaction has been utilised. The proposed mechanism for the reaction and the factors that influence the product distribution will also be introduced. 

Gordon, C. M., Kiszka, M., Dunkin, I. R., Kerr, W. J., Scott, J. S., Gebicki, J. Elucidating the mechanism of the photochemical Pauson-Khand reaction matrix photochemistry of (phenylacetylene)hexacarbonyldicobalt. J. Organomet. Chem. 1998, 554,147-154. 

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. 

The proposed mechanism is shown in (Scheme 43). Based on the results of allenic Pauson-Khand type reaction (PKTR), it is known that the Rh catalyst preferentially coordinates to the distal double bond of the allene-forming metallacycle I-I and sequential CO insertion would provide [2-I-2-1-1] product. However, in the absence of CO /3-hydride elimination takes place instead leading to triene intermediate I-II, and subsequent reductive elimination affords the cross-conjugated triene 83. 

Finally, Cramer and co-workers described an alternative route to classical Pauson-Khand reaction for the synthesis of cyclopentenones. The proposed procedure involves a reductive Ni -catalyzed [3+2] cycloaddition between aryl enoates and internal alkynes. More interestingly, the use of a chiral NHC led to a highly enantioselective reaction [eqn (10.38)]. Note that with unsymmetric alkynes the reaction is also regioselective. A plausible mechanism was proposed with the hypothesis that facial-selective coordination and incorporation of the enoate are controlled by a single chiral side chain of the carbene. 

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