Pauson-Khand

Asymmetric Pauson-Khand reaction in syntheses of heterocycles fused with five-member carbocyclic fragment 980PP121. 

The reaction of an alkyne 1 and an alkene 2 in the presence of dicobaltoctacar-bonyl to yield a cyclopentenone 3 is referred to as the Pauson-Khand reaction Formally it is a [2 + 2 + 1 ]-cycloaddition reaction. The dicobaltoctacarbonyl acts as coordinating agent as well as a source of carbon monoxide. 

An example for the synthetic potential is the formation of a fenestrane skeleton 11 from the open-chain compound 10 by a cascade of two consecutive intramolecular Pauson-Khand reactions, the yield in this case is however only 9% J... 

The Pauson-Khand reaction was originally developed using strained cyclic alkenes, and gives good yields with such substrates. Alkenes with sterically demanding substituents and acyclic as well as unstrained cyclic alkenes often are less suitable substrates. An exception to this is ethylene, which reacts well. Acetylene as well as simple terminal alkynes and aryl acetylenes can be used as triple-bond component. 

RCM of 132 to the medium-sized enyne 135, for example, appears to be highly unlikely. This transformation was achieved by conversion of 132 to the cobalt complex 133, which is cyclized to the protected cycloenyne 134. Deprotection yields 135, and a subsequent Pauson-Khand reaction yields the interesting tricyclic structure 136 (Scheme 27) [125c]. 

An interesting family of polycyclic pyrroles was described in 2005 using again the synthetic sequence of a Stetter reaction for the preparation of the starting 1,4 diketones followed by a microwave-assisted Paal-Knorr condensation [35]. For example, cyclopentenone 23 (obtained in a Pauson-Khand cyclization) reacted imder Stetter reaction conditions to give the amino ketone 25 (Scheme 8). The microwave-assisted Paal-Knorr cyclization of 25 with different amines gave a small collection of tricychc pyrrole 2-carbox-amides. 

The reaction of alkenes with alkenes or alkynes does not always produce an aromatic ring. An important variation of this reaction reacts dienes, diynes, or en-ynes with transition metals to form organometallic coordination complexes. In the presence of carbon monoxide, cyclopentenone derivatives are formed in what is known as the Pauson-Khand reaction The reaction involves (1) formation of a hexacarbonyldicobalt-alkyne complex and (2) decomposition of the complex in the presence of an alkene. A typical example Rhodium and tungsten ... 

The thermally induced Pauson-Khand intramolecular cyclization of 57 leads to tricycHc enones in moderate yields and with variable diastereoselectivities <96T14021>. 

Mukai, C., Yoshida, T., Sorimachi, M., Odani, A. (2006) Co2(CO)8-Catalyzed Intramolecular Hetero-Pauson-Khand Reaction of Alkynecarbodiimide Synthesis of ( )-Physostigmine. Organic Letters, 8, 83-86. 

Scheme 10.67 Intermolecular Pauson-Khand reactions with PuPHOS and CyPHOS.

The intermolecular Pauson-Khand reaction of the resulting S/P-cobalt complexes with norbornadiene was studied under thermal and A -oxide activation conditions. Thus, heating the diastereomerically pure complex (R = Ph, R = Cy) with ten equivalents of norbornadiene at 50 °C in toluene afforded the corresponding exo-cyclopentenone in a quantitative yield and with an enantio-selectivity of 99% ee. Under similar conditions, the analogous trimethylsilyl complex (R = TMS, R = Cy) afforded the expected product in a high yield but with a lower enantioselectivity of 57% ee. In order to increase this enantio-selectivity, these authors performed this reaction at room temperature in dichloromethane as the solvent and in the presence of NMO, which allowed an enantioselectivity of 97% ee to be reached. These authors assumed that the thermal activation promoted the isomerisation of the S/P ligand leading to a nonstereoselective process. 

Scheme 10.69 Intermolecular Pauson-Khand reactions of amido-alk5mes with PuPHOS and CamPHOS-derived ligands.

TRANSITION-METAL CATALYZED CYCLOADDITIONS 4.3.1 Pauson-Khand-Type Reactions... 

The Pauson-Khand reaction (PKR) is an efficient method to synthesize cyclopentenones.105 The reaction is usually carried out in organic solvent. The first aqueous Pauson-Khand reaction was reported by... 

Later, Chung et al. successfully developed an intramolecular Pauson-Khand reaction in water without any cosolvent by using aqueous colloidal cobalt nanoparticles as catalysts. The catalyst was prepared by reducing an aqueous solution of cobalt acetate containing sodium dode-cyl sulfate (SDS) surfactant. The cobalt nanoparticle could be reused eight times without any loss of catalytic activity (Eq. 4.57).107... 

One of the best methods to synthesize cyclopentenone derivatives is the Pauson-Khand procedure. However, Shindo s group have recently developed a domino process consisting of a [2+2] cycloaddition of a ketone with anynolate, followed by a Dieckmann condensation to give a 3-lactone as 4-190 which is decarboxylated under reflux in toluene in the presence of silica gel to afford cyclopentenones [64a]. Thus, the reaction of 4-188 and 4-189 led to 4-190, which on heating furnished the linear cucumin 4-191 (Scheme 4.41). This natural product has been isolated from the mycelial cultures of the agaric Macrocystidia cucumis [65, 66]. The domino procedure described was also used to synthesize dihydrojasmone and a-cuparenone. Moreover, the [2+2] cycloaddition can be combined with a Michael reaction [64b]. 

Scheme 6/3.25. Domino metathesis/Pauson-Khand reaction.

A combination of a metathesis and a Pauson-Khand reaction, which leads to tricyclic compounds starting from diene-ynes, has been described by Perez-Castells and colleagues [262]. Treatment of the Co-complex 6/3-86, obtained from the corresponding alkyne in 75 % yield, with 5 mol% of the Ru-catalyst 6/3-13 for 18 h, followed by addition of an N-oxide as trimethylamine-N-oxide (TMANO) or NMO as copromoters, gave 6/3-87 in 81% yield. 

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