Pauson-Khand reaction carbonyls

A combination of Co-mediated amino-carbonylation and a Pauson-Khand reaction was described by Pericas and colleagues [286], with the formation of five new bonds in a single operation. Reaction of l-chloro-2-phenylacetylene 6/4-34 and dicobalt octacarbonyl gave the two cobalt complexes 6/4-36 and 6/4-37 via 6/4-35, which were treated with an amine 6/4-38. The final products of this domino process are azadi- and azatriquinanes 6/4-40 with 6/4-39 as an intermediate, which can also be isolated and separately transformed into 6/4-40 (Scheme 6/4.11). 

Under the conditions of the cobalt-mediated carbonylative A-oxide-promoted cocyclization (Pauson-Khand reaction) at room temperature, compound 547 provides exocyclic 1,3-diene 548 as the major product (>98%) together with only traces of the corresponding carbonylative product 549. Owing to the relative instability of the diene, it is more efficient to perform a one-pot cobalt cyclization/Diels-Alder process after A-oxide-promoted cyclization of the cobalt complexes. Compound 550 is obtained as a single diastereomer in 39% overall yield if MTAD is used as a dienophile (Scheme 90) <2003JOC2975>. 

Abstract The transition metal mediated conversion of alkynes, alkenes, and carbon monoxide in a formal [2 + 2+1] cycloaddition process, commonly known as the Pauson-Khand reaction (PKR), is an elegant method for the construction of cyclopentenone scaffolds. During the last decade, significant improvements have been achieved in this area. For instance, catalytic PKR variants are nowadays possible with different metal sources. In addition, new asymmetric approaches were established and the reaction has been applied as a key step in various total syntheses. Recent work has also focused on the development of CO-free conditions, incorporating transfer carbonylation reactions. This review attempts to cover the most important developments in this area. 

Recent developments have impressively enlarged the scope of Pauson-Khand reactions. Besides the elaboration of strategies for the enantioselective synthesis of cyclopentenones, it is often possible to perform PKR efficiently with a catalytic amount of a late transition metal complex. In general, different transition metal sources, e.g., Co, Rh, Ir, and Ti, can be applied in these reactions. Actual achievements demonstrate the possibility of replacing external carbon monoxide by transfer carbonylations. This procedure will surely encourage synthetic chemists to use the potential of the PKR more often in organic synthesis. However, apart from academic research, industrial applications of this methodology are still awaited. 

The asymmetric reactions discussed in this chapter may be divided into three different types of reaction, as (1) hydrometallation of olefins followed by the C—C bond formation, (2) two C C bond formations on a formally divalent carbon atom, and (3) nucleophilic addition of cyanide or isocyanide anion to a carbonyl or its analogs (Scheme 4.1). For reaction type 1, here described are hydrocarbonyla-tion represented by hydroformylation and hydrocyanation. As for type 2, Pauson-Khand reaction and olefin/CO copolymerization are mentioned. Several nucleophilic additions to aldehydes and imines (or iminiums) are described as type 3. 

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. 

Other solid-phase preparations of carbonyl compounds include the hydrolysis of acetals (Table 12.4), inter- [52] and intramolecular Pauson-Khand reactions, the isomerization of allyl alcohols, and the a-alkylation and a-arylation of other ketones. Tietze reported the generation of acetoacetyl dianions on cross-linked polystyrene and their selective alkylation at C-4 (Entry 6, Table 12.4). The use of weaker bases resulted in single or twofold alkylation at C-2 [53]. 

Bicyclic cyclotrigermanes, thermolysis, 3, 793 Bicyclic imidazoles, via intramolecular C-H functionalizations, 10, 138 Bicyclic siloxanes, rational synthesis, 3, 655 Bicycloctasilane dianion, preparation, 3, 466468 Bicyclo[5.3.0]decadiene, via [5+2]-cycloadditions, 10, 613 Bicyclo[5,3,0]-decanes, via Pauson-Khand reaction, 11, 361 Bicyclononasilane anions, preparation, 3, 466-468 Bicyclo[3.3.0]-octanones, via carbonylative carbocyclization, 11, 427... 

Cyclobutenes, in Pauson-Khand reaction, 11, 352 Cyclocarbonylation reactions, alkynes, 10, 714 Cyclo-C3 complexes, with molybdenum carbonyls, 5, 440 Cyclo-C4 complexes, in molybdenum carbonyls, 5, 448 Cyclochrome P450cam, aryldiazene reactions, 6, 107 Cyclodextrins... 

Oxidative alkoxycarbonylation asymmetric carbonylation, 11, 467 catalyst development, 11, 467 mechanism, 11, 466 Oxidative amination, olefins, 10, 155 Oxidative cleavage, mechanisms, 1, 103 Oxidative promoters, in Pauson-Khand reaction with dicobalt octacarbonyl, 11, 337... 

Alkyne-alkene carbonylative coupling. Intramolecular carbonylative coupling of dialkynes catalyzed by Fe(CO)3 provides a route to cyclopentadienones (equation I). The more difficult carbonylative alkyne-alkene coupling to provide cyclopen-tenones (Pauson-Khand reaction) can also be effected with Fe(CO)s, but in modest yield. In an improved coupling, acetone is treated with Fe2(CO)9 to form Fe-... 

Ruthenium carbonyl complexes have been shown to catalyze a number of car-bonylation processes. The ruthenium-catalyzed intramolecular Pauson-Khand reaction was found to proceed in the presence of Ru3(CO)12 (Eq. 105) [165,166]. The reaction is a valuable tool for selective organic synthesis. 

The Pauson-Khand reaction starts with the replacement of two CO molecules, one from each Co atom, with the alkyne to form a double a complex with two C-Co a bonds, again one to each Co atom. One CO molecule is then replaced by the alkene and this n complex in its turn gives a a complex with one C-Co a bond and one new C-C a bond, and a C-Co bond is sacrificed in a ligand coupling reaction. Then a carbonyl insertion follows and reductive elimination gives the product, initially as a cobalt complex. 

Although a whole series of carbonyl complexes of other transition metals (Fe, Mo, W, Ni) could only be used in stoichiometric Pauson-Khand reactions [11], two Japanese laboratories have since independently reported efficient ruthenium-catalyzed (intramolecular) reactions. The desired cy-clopentenones are formed in good to excellent yields in dimethylacetamide [12] or dioxane [13] in the presence of 2 mol% of [Ru3(CO),2] at 140-160 °C and 10-13 atm CO pressure. 

Considerable efforts have been made to develop asymmetrical variants of the classical Pauson-Khand reaction. Initial investigations have shown that compounds derived from cobalt complexes of type 1, in which a carbonyl ligand is replaced by a chiral phosphane (glyphos), react with high enantioselectivity [22], However, the procedure is too complex to be of preparative value. The concept of Kerr et al., who achieved significant enantioselectivities (max. 44 % ee) in intermolecular Pauson-Khand reactions by... 

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. 

Co2(CO)g has been used in numerous reactions in addition to the plethora of substitution reactions that it undergoes with phosphines, nitrosyls, alkynes, and so forth. Many of these substituted carbonyl complexes and their reactions have been discussed elsewhere in this report. One area in which Co2(CO)g has received much attention is catalysis two classes of catalytic reactions of which Co2(CO)g plays a major role are hydroformylation (see Hydroformylation) and Pauson Khand cycloaddition (see Pauson-Khand Reaction). 

Prior to the development of enyne bicyclization reactions promoted by Zr and other Group IV metals, the Co-catalyzed enyne bicyclization-carbonylation reaction (the Pauson-Khand reaction ) was known. This reaction is discussed in Volume 5, Chapter 9.1. In the Pauson-Khand reaction, the overall transformation is the conversion of enynes into bicyclic enones, and the organometallic bicyclic intermediates are usually neither readily available nor isolated. The use of Co2(CO)s, an 18-electron species, necessitates relatively high reaction temperatures. These and other limitations suggested the desirability of developing alternative enyne bicyclization reactions. 

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