Khand reaction

Paulson-Khand Reaction Tetrahedron 1985, 41, 5855 Organic Reactions 1991, 40,1. 

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]. 

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 ... 

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.

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... 

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. 

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 Pauson-Khand reaction is the Co-induced formation of cyclopentenones from ene-ynes and CO. One impressive example of a domino Pauson-Khand process is the synthesis of fenestrane 6/4-15, as reported by Keese and colleagues [278]. The transformation is initiated by a double Grignard reaction of 4-pentynoic acid 6/4-12, followed by protection of the formed tertiary hydroxyl group to give 6/4-13. The Co-induced polycyclization of 6/4-13 led directly to the fenestrane 6/4-15... 

It is not quite clear which step takes place first - the Co-catalyzed [2+2+1] cycloaddition of the outer alkyne moiety, or the Diels-Alder reaction of the diene with the inner alkyne to form a 1,4-cyclohexadiene, which then undergoes a Pauson-Khand reaction with the remaining alkyne. Recently, it has been shown that a domino reaction can also be performed using 1 mol of a 1,7-diphenyl-1,6-diyne 6/4-20 and a 1,3-diene 6/4-21 in the presence of Co/C at 150 °C under 30 atm CO, to give the polycyclic compounds 6/4-22 as sole product (Scheme 6/4.7) [282]. 

The Pauson-Khand reaction can be facilitated by preparing the necessary ene-yne in situ by an allylic substitution of an alkyne with allylic acetate using a Pd°- and Rh-catalyst The yield of the cydization product 6/4-24 ranges from 0 % with X = O (6/4-24a) to 92% with X=NTs, as well as X = C(C02Et)2 (6/4-24c) (Scheme 6/4.8) [283],... 

Scheme 6/4.8. Combination of a nucleophilic substitution and a Pauson-Khand reaction.

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). 

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