Cobalt carbonyl cycloaddition

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. 

Pauson-Khand Cycloaddition. Pauson Khand cycloaddition (see Pauson-Khand Reaction) is a cobalt-mediated method to prepare cyclopentenone from the cyclization of an alkyne with an alkene and CO (equation 14). This method is widely used to produce cychc ketones. Originally, stoichiometric amounts of Co2(CO)g were used in these reactions with the cobalt carbonyl being the CO source. However, it was shown that a strict temperature profile and high-purity reagents allowed the use of catalytic amounts of Co2(CO)g for reactions with 1 atm of CO. Currently, there is intense interest in developing catalytic cobalt starting materials for use in Pauson-Khand reactions. 

An additional advantage of the intramolecular protocol stems from the opportunity to prepare easily the required polyfunctional precursors via cobalt carbonyl stabilized propargyl cations. The approach based on the tandem utilization of Co-mediated alkylation and Pauson-Khand annulation was developed in Schreiber s studies to elaborate short pathways for the synthesis of polycyclic compounds. An example of the efficiency of this protocol is the two-step transformation of the acyclic precursor 409 into the tricyclic derivative 410. The cobalt-complexed acetal 409 was first transformed into the cyclooctyne derivative 411 via intramolecular reaction of the in situ generated propargyl cation 409a with the allylsilane moiety. Cyclooctyne 411 underwent smooth cycloaddition in the presence of carbon monoxide to give the target compound 410 with excellent stereoselectivity. 

The resulting heterocycles in the complex may be further reduced or desilylated (either in the complex or after demetallation). Further synthetic potential exists in the use of the primary products, obtained by cobalt-mediated cycloadditions, as synthons in organic chemistry. For example, indole derivatives have been co-cyclized at the j/ -Cp-cobalt catalyst to give 4a,9a-dihydro-9//-carbazoles or, after oxidation, precursors for strychnine [50]. Remarkably, the cycloaddition of acrolein in the presence of a small amount of methyl acetate occurs at the carbonyl, rather than at the C=C double bond, to give vinylpyran selectively (eq. (19)) [48]. 

Apart from cobalt carbonyl catylyzed hydroformylation, Pauson-Khand (PK) reaction is another type of reaction catalyzed with bimetallic carbonyl complex. Formally Pauson-Khand (PK) is a [2 -i- 2 -i- 1] cycloaddition of an alkyne, an alkene, and a CO group into cyclopentenone [128-130]. This process was initially discovered in 1973 [131], and early studies focused on using dicobalt octacarbonyl as both reaction mediator and the source of the carbonyl functional group. Since several variants of the original thermal protocol were introduced, PK reaction has received more and more fundamental and organic synthesis interests [132, 133]. 

Chapter 17 closes with a brief presentation of the Pauson-Khand reaction. The Pauson-Khand reaction (PKR) is a formal [2+2+1] cycloaddition reaction involving an alkyne, an alkene, and carbon monoxide to form a cyclopentanone shown generically in Equation 17.71. The Pauson-Khand reaction was initially reported as a stoichiometric reaction mediated by cobalt carbonyl, but it has been translated into a catalytic process in recent years. Most recently, it has developed into an enantioselective catalytic process. Complexes of Ti, Mo, W, Fe, Co, Ni, Ru, Rh, Ir, and Pd have all been shown to catalyze this reaction. 

Chiral salen chromium and cobalt complexes have been shown by Jacobsen et al. to catalyze an enantioselective cycloaddition reaction of carbonyl compounds with dienes [22]. The cycloaddition reaction of different aldehydes 1 containing aromatic, aliphatic, and conjugated substituents with Danishefsky s diene 2a catalyzed by the chiral salen-chromium(III) complexes 14a,b proceeds in up to 98% yield and with moderate to high ee (Scheme 4.14). It was found that the presence of oven-dried powdered 4 A molecular sieves led to increased yield and enantioselectivity. The lowest ee (62% ee, catalyst 14b) was obtained for hexanal and the highest (93% ee, catalyst 14a) was obtained for cyclohexyl aldehyde. The mechanism of the cycloaddition reaction was investigated in terms of a traditional cycloaddition, or formation of the cycloaddition product via a Mukaiyama aldol-reaction path. In the presence of the chiral salen-chromium(III) catalyst system NMR spectroscopy of the crude reaction mixture of the reaction of benzaldehyde with Danishefsky s diene revealed the exclusive presence of the cycloaddition-pathway product. The Mukaiyama aldol condensation product was prepared independently and subjected to the conditions of the chiral salen-chromium(III)-catalyzed reactions. No detectable cycloaddition product could be observed. These results point towards a [2-i-4]-cydoaddition mechanism. 

Alkynols complexed to cobalt can be oxidized to alkynals without decomplexation. Propargyl aldehydes are protected from polymerization upon complexation with Co2(CO)6. These aldehydes smoothly undergo Wittig-type reactions. Carbonyl-ene reactions have been demonstrated (Scheme 194). Complexation to cobalt protected the enyne in complex (132) from Michael-type reactions (Scheme 195). Alkenyl-substituted complexes undergo [3 + 2]cycloadditions with nitrile A-oxides (Scheme 196). 

Stable, isolable metallacycles are also obtained from reaction of complexes that serve as sources of the CpCo fragment (e.g. CpCo(PPh3)2) and alkynes. Upon carbonylation diese typically give high yields of cobalt-complexed cyclopentadienones. Direct reaction of CpCo(CO)2 with alkynes is similarly useful. The cycloaddition of di(t-butoxy)acetylene upon photolysis with CpCo(CO)2 is an example (Scheme 5). In all these systems the final complexes lack coordinated CO, and therefore amine oxides are not suitable reagents for liberating the stable cyclopentadienones. Tetra(t-butoxy)cyclopentadienone is accessible on a preparative scale via controlled electrochemical oxidation. Other oxidants such as Cr have been used as well in other systems. 

The catalytic [2 + 2 + 1]-cycloaddition reaction of two carbon—carbon multiple bonds with carbon monoxide has become a general synthetic method for five-membered cyclic carbonyl compounds. In particular, the Pauson-Khand reaction has been widely investigated and established as a powerful tool to synthesize cyclopentenone derivatives.110 Various kinds of transition metals, such as cobalt, titanium, ruthenium, rhodium, and iridium, are used as a catalyst for the Pauson-Khand reaction. The intramolecular Pauson-Khand reaction of the allyl propargyl ether and amine 91 produces the bicyclic ketones 93, which bear a heterocyclic ring as shown in Scheme 31. The reaction proceeds through formation of the bicyclic metallacyclopentene intermediate 92, which subsequently undergoes insertion of CO to give 93. 

---