P.-K. reaction

Among the carbonylative cycloaddition reactions, the Pauson-Khand (P-K) reaction, in which an alkyne, an alkene, and carbon monoxide are condensed in a formal [2+2+1] cycloaddition to form cyclopentenones, has attracted considerable attention [3]. Significant progress in this reaction has been made in this decade. In the past, a stoichiometric amount of Co2(CO)8 was used as the source of CO. Various additive promoters, such as amines, amine N-oxides, phosphanes, ethers, and sulfides, have been developed thus far for a stoichiometric P-K reaction to proceed under milder reaction conditions. Other transition-metal carbonyl complexes, such as Fe(CO)4(acetone), W(CO)5(tetrahydrofuran), W(CO)5F, Cp2Mo2(CO)4, where Cp is cyclopentadienyl, and Mo(CO)6, are also used as the source of CO in place of Co2(CO)8. There has been significant interest in developing catalytic variants of the P-K reaction. Rautenstrauch et al. [4] reported the first catalytic P-K reaction in which alkenes are limited to reactive alkenes, such as ethylene and norbornene. Since 1994 when Jeong et al. [5] reported the first catalytic intramolecular P-K reaction, most attention has been focused on the modification of the cobalt catalytic system [3]. Recently, other transition-metal complexes, such as Ti [6], Rh [7], and Ir complexes [8], have been found to be active for intramolecular P-K reactions. 

In 1997, Murai et al. [9] reported the first use of Ru3(CO)12 as a catalyst for the intramolecular P-K reaction of 1,6-enynes (Eq. 1). The scope of the reaction with respect to the alkene is limited to enynes with no substituent on the olefinic carbon. The metallacycle 1 is proposed to be involved as an intermediate. 

Pauson-Khand reaction. The intermolecular Pauson-Khand reaction of N- 2-alkenoyl)bomane-IO,2-sultams is totally stereoselective. The catalytic P-K reaction is promoted by small quantities of DME (or other hard bases including water). Reactions carried out in supercritical carbon dioxide are very efficient regardless of the substitution pattern of the alkyne unit. ... 

Note that tetracobalt dodecacarbonyl is a catalyst precursor for reaction at 150 and 10 atm CO. Only 0.01 equiv of the cobalt cluster is required. Actually catalytic amount of Co2(CO)g of high purity is sufficient to complete the intramolecular P-K reaction, also the hexacarbonyldicobalt complex of 2-methyl-3-butyn-2-ol can be decomposed with triethylsilane to generate an active cobalt carbonyl catalyst. ... 

I Khand reaction of N- 2- . catalytic P-K reaction is e-. aiding water). Reactions r a jardless of the substitution... 

T reaction at 150° and 10 ually catalytic amount of ar P-K reaction, also the be decomposed with... 

Pauson-Khandreaction. DMSO-Me S promotes intramolecular P-K reaction to form 3-thiabicyclo[3,3,0]oct-5-en-7-ones. 

The P-K reaction is regioselective for cycloaddition of substituted alkynes, yielding a cyclopentenone in which the larger alkyne substituent is usually adjacent to the keto group. Stereochemistry about 1,2-disubstituted alkenes is typically preserved upon cycloaddition however, if the substituents are different, both regioisomers will form. The reaction is quite sensitive to the nature of the alkene. Tri- and tetra-substituted olefins are unreactive, and the order of... 

For a good review of the mechanism of the P-K reaction, see S. Laschat, A. Becheanu, T. Bell, and A. Baro, Synlett, 2005, 2547. 

The first examples of the P-K reaction required high temperatures and pressures to succeed. Several improvements in yield and reaction rate have resulted from continued research efforts over the past 30 years. These include the addition of silica gel200 to the reaction mixture (adsorption of the alkyne-Co complex onto silica may restrict molecular motion, allowing the ene-yne system to interact more readily also, lack of solvent would allow bimolecular reactions to proceed faster) the use of tertiary amine A-oxidcs 201-202 the application of photochemical conditions to ease departure of CO in the rate-determining step and the inclusion of various Lewis bases, which help stabilize intermediate Co complexes.203... 

For good reviews on recent advances in improving the efficacy of intermolecular P-K reactions, see Footnote 196 and S. E. Gibson and N. Mainolfi, Angew. Chem. Int. Ed., 2005, 44, 3022. 

Two relatively recent advancements that have increased the utility of the P-K reaction include (1) allowing the reaction to run with catalytic amounts of transition metal and (2) making the transformation asymmetric. Several metals beside Co will catalyze the P-K reaction, including Rh, Ir, Fe, Ru, Group 6 metals, and Ti. Much of the work in catalyst development has focused on use of Rh(I) and Ru(II) complexes, which seem to be most effective. Many Rh precatalysts have been used, such as Rh3(CO)12, Wilkinson s catalyst, and complexes 103 and 104. AgOTf is often used in conjunction with the last three catalysts to remove Cl, which then produces more catalytically active cationic Rh(I) species. 

Equation 12.97 illustrates use of catalyst 104 in the synthesis of a bicyclic ring system.207 Note that the presence of a catalyst also allows the transformation to occur under a CO pressure of 1 bar. Equation 12.98 demonstrates a clever application of the so-called traceless tether method for running a Ru-catalyzed P-K reaction.208 Although this is an intermolecular P-K reaction, the alkene is tethered to a pyridylsilyl group (compound 105), which directs regioselective reaction of the alkene fragment with the alkyne. The presence of residual H20 in the reaction mixture removes the silyl group, which can be recycled. 

Chemists have investigated asymmetric P-K reactions, using chiral diphosphine and diphosphite ligands to induce enantioselectivity. When (,S )-BINAP was added to a catalytic amount of Co4(CO)12, (S)-bicyclic ketone 106 formed in 55% yield with an ee of 88% (equation 12.99). Experimental evidence suggested that the active catalyst was dicobalt complex 107, in which BINAP binds in bidentate... 

A Rh-catalyzed Pauson-Khand reaction is shown below. Sometimes an aldehyde (RCHO) is used as a source of CO.227 Assume that the Rh catalyst is of the form L Rh(I), and the by-product of the P-K reaction is R-H. 

The use of both LIU and HIU has been shown to increase the efficiency of the P-K reaction, which involves the formation of cyclopentenone from the annulation of a cobalt alkynyl carbonyl complex and an alkene. The use of low-power ultrasound, as for example, from a cleaning bath, although capable of producing intramolecular P-K reactions, generated relatively low cyclization yields. The motivation for the use of high intensity came from its ability, as previously described, to effectively decarbonylate metal carbonyl and substituted metal carbonyl complexes. Indeed, HIU produced by a classic horn-type sonicator has been shown to be capable of facile annulation of norbornene and norbornadiene in under 10 min in the presence of a trimethylamine or trimethylamine N-oxidc dihydrate (TMANO) promoter, with the latter promoter producing cleaner product mixtures. This methodology also proved effective in the enhancement of the P-K reaction with less strained alkenes such as 2,5-dihydrofuran and cyclopentene, as well as the less reactive alkenes -fluorostyrene and cycloheptene. The mechanism has been postulated to involve decarbo-nylation of the cobalt carbonyl alkyne, followed by coordination by the amine to the vacant coordination sites on the cobalt. 

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