2-cyclopentenone alkene 2350 Transformation

Co-catalyzed transformations are concerned mainly with the [2+2+2] cycloadditions of three alkyne groups to give arenes. Another important reaction is the [2+2+1] cycloaddition of alkynes, alkenes and CO to give cyclopentenones, which is the well-known as Pauson-Khand reaction [272]. 

The [2+2+1] cycloaddition of an alkene, an alkyne and carbon monoxide is commonly known as the Pauson-Khand reaction. This transformation has been adopted many times in the synthesis of complex natural products and related compounds, which contain a cyclopentenone moiety, for example, prostaglandins. Two independent reports of this reaction appeared almost simultaneously in late 2002 by Iqbal and co-workers25 and Fisher and co-workers26, respectively. They not only used very similar substrate systems in their studies, but they also reached very similar conclusions Toluene was found to be the preferred solvent in this reaction, even though it is a very poor microwave absorber. A reaction time between 5 and 10 min, using dicob alto ctacar-bonyl or dicobalthexacarbonyl as the carbon monoxide source, and a temperature of 100-120°C resulted in high yields of the products. Fisher and co-workers used 20 mol% Co2(CO)8 and cyclohexylamine as an additive (Scheme 5.12), since this system had been used previously in order to allow a catalytic reaction. Iqbal and co-workers did not use cyclohexylamine, but instead used 1 equiv. of the carbon monoxide (Co2(CO)6) source. In both reports, the products were formed in 40-70% yield. 

A significant advance in the use of Friedel-Crafts acylation of alkenes to prepare divinyl ketones was the employment of vinylsilanes to control the site of electrophilic substitution. Two groups have developed this approach to cyclopentenone annulation using slightly different strategies. In the method described by Magnus the reagent vinyltrimethylsilane (80) is used primarily as an ethylene equivalent (equation 44). The construction of bicyclic systems followed readily as Nazarov cyclization proceeded under the reaction conditions. Tin(lV) chloride was found to be the most effective promoter of the overall transformation. As expected the position of the double bond is thermodynamically controlled. 

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... 

The mechanism of this transformation is unclear at the present time, but two possibilities are pictured below. In the first (Fig. 5), loss of a CO ligand and binding of the acetylene initially provides the T -alkyne complex 17. Subsequent loss of a second equivalent of CO allows for coordination of the alkene to give 17a. Insertion of the olefin into the titanium-carbon bond of the alkyne complex produces metallacyclopentene 18. The insertion of CO generates acyl complex 19 which, upon reductive elimination, yields the observed cyclopentenone product. A second plausible mechanism (Fig. 6) involves initial formation of metal-... 

In the presence of octacarbonyldicobalt, three-component cycloaddition of acetylenes occurs with alkenes and carbon monoxide, affording cyclopentenones. Although thermal activation of the organometallic was the original method of effecting this transformation, a variety of reaction additives have since been explored, resulting in procedures that permit the... 

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... 

---