Norbornenes Pauson-Khand reaction

It has also been found that the indolizinoquinoline iV-oxidc 291 can be used as a chiral promoter in enantioselective Pauson-Khand reactions in the reaction of norbornene with various alkynes, ee s of up to 33% were obtained in the presence of this promoter <1998H(48)1445>. 

An important procedure for the synthesis of cyclopentenones is the so-called Pauson-Khand reaction, which constitutes a formal [2 + 2 + 1] cycloaddition of an alkene, an alkyne, and carbon monoxide. Due to the increase in structural diversity of the available starting materials, the reaction has become an attractive target for scientific investigations [1-8]. The first successful example was reported by Pauson, Khand et al [9] in 1973 for the conversion of norbornene with the phenylacetylene-hexacarbonyldicobalt complex to give the corresponding cyclopentenone in 45% yield (Eq. 1). 

Ethynylcyclopropanes, like normal acetylenes, react with dicobalt octacarbonyl in ether to form stable dinuclear cluster-like hexacarbonyl complexes (equation 170). The complex with l-chloro-2,2,3,3-tetramethylethynylcyclopropane reacts stereo- and regioselec-tively with norbornene in a typical Pauson-Khand reaction to give the xo-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)-c/.y-bicyclo[3.3.0]oct-3-en-2-one (equation 172) ... 

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]. 

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. 

It is accepted that this reaction involves the formation of the alkynedicobalt hexacarbonyl complex from an alkyne and Co2(CO)s by the evolving of two CO ligands, followed by the alkene coordination at one of the two enantiotopic Co atoms with concomitant CO insertion, and final reductive elimination of the metal to an a,(3-unsaturated cyclopentenone. In the traditional protocol, the reaction mixture is heated in toluene at 110°C, or tertiary amine A-oxides are added to promote the reaction at ambient temperature. For the purpose of stereochemical control, many Pauson-Khand reactions are designed as intramolecular reactions P " or using cyclic alkenes, such as norbornene. It has been found that the reactivity of cyclic alkenes is in the order of cyclohexene < cyclopentene < norbornene. For the intermolecular Pauson-Khand reaction, alkene is positioned adjacent to the less bulky acetylenic substituent during coordination because of steric hindrance, and a subsequent C-C bond forms between an alkenic... 

A 1 1 mixture of PdCl2 and thiourea (5 mol%) has been reported to catalyse the Pauson-Khand reaction of norbornene with substituted alkynoates RC=CC02R. Interestingly, addition of LiCl has been found to reverse the regioselectivity. ... 

Photochemical intermolecular and intramolecular Pauson-Khand reactions of the allq ne cobalt complexes [RC=CH Co(CO)3 2] with alkenes using a flow microreactor were reported. The reaction of [PhC=CH Co(CO)3 2] with norbornene in a batch reactor led to the product in 32% yield, while the flow reactor resulted in 88% yield. " ... 

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. 

The first report of a catalytic intermolecular cyclization was made by Pauson and Khand in 1974 [22], but the scope was limited to gaseous acetylene as the alkyne partner, strained olefins such as norbornene and norbornadiene as the alkene component, and TON s (turnover numbers) were modest (8-11). Several subsequent reports detailed the production of cyclopentenones from a substoi-chiometric amount of Co2(CO)g, but none were as efficient as Pauson s initial work [23,24]. Using ethylene as the alkene component, Rautenstrauch demonstrated the first efficient catalytic Pauson-Khand cyclization with a TON of 220, Eq. (5) [25]. A more general catalyst system employing (indenyl)Co(cod) was recently reported by Chung and Jeong, Eq. (6) [26]. The reaction was quite effec-... 

There are several examples known where methylenecyclopropanes have been employed as cosubstrates in reactions of the Khand—Pauson type. Generally, this cobalt-mediated reaction is performed with hexacarbonyldicobalt complexes of alkynes, preferably strained alkenes such as norbornene or cyclobutene, and carbon monoxide to produce cyclopent-2-enones. Stoichiometric amounts of cobalt (in the form of the alkyne complexes) are normally needed. Methylenecyclopropane (1) can be employed as the strained alkene and reacts with a variety of alkynes to yield spiro-fused products. Silica gel or zeolites function as promoters of the reaction, giving rise to improved yields. ... 

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