Enantioselectivity Pauson-Khand reaction

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. 

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>. 

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. 

An enantioselective intramolecular Pauson-Khand reaction based on chiral auxiliary-directed 7t-face discrimination in acetylenic 0-alkyl enol ether-dicobalt hexacarbonyl complexes, which proceeds with good yields and high facial diastereoselectivity, has recently been developed by M.A. Pericas, A. Moyano, A.E. Greene and their associates. The method has been applied to an enantioselective formal synthesis of hirsutene. Moreover, the process is stereodivergent and the chiral auxiliary -rran5-2-phenylcyclohexanol- is recovered in a yield as high as 92% [18]. 

Table 5 The catalytic enantioselective Pauson-Khand reaction...

One of the earliest enantioselective carbon-carbon bond-forming processes catalyzed by chiral transition-metal complexes is asymmetric cyclopropanation discussed in Chapter 5, which can proceed via face-selective carbometallation of carbene-metal complexes. Some other more recently developed enantioselective carbon-carbon bond forming reactions, such as Pd-catalyzed enantioselective alkene-CO copolymerization (Chapter 7) and Pd-catalyzed enantioselective alkene cyclization (Chapter 8.7), are thought to involve face-selective carbometallation of acy 1-Pd and carbon-Pd bonds, respectively (Scheme 4.4). Similarly, the asymmetric Pauson-Khand reaction catalyzed by chiral Co complexes most likely involves face-selective cyclic carbometallation of chiral alkyne-Co complexes (Chapter 8,7). 

Transition metal complexes other than Co2(CO)8 catalyse the Pauson Khand reaction. The complex [RhCl(CO)2]2 catalyses the reaction of 224 [97], and Ru3(CO)12 [98] also catalyses these reactions at somewhat high temperatures. Highly enantioselective cyclization of 225 is catalysed by the chiral Ti(ebthi) complex to give 226 with 94% ee [99]. 

The cyclopenta[c]pyran system 6 is formed when allenyl propynyl ethers are heated in CO in the presence of Co/Rh nanoparticles a Pauson-Khand reaction is involved <07SL453>. An enantioselective Bronsted acid-catalysed Nazarov cyclisation of a dihydropyran-based divinylketone affords cyclopenta[/>]pyrans 7 <07AG(E)2097> and Sc and In triflates catalyse a similar reaction of 6-alkenoyl derivatives of both dihydropyran and thiopyran <07S1733>. 

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... 

Enantioselectivities up to 44 % were reached in intermolecular PKRs when chiral aminoxides R 3N—>0 were used [19]. Although the mechanism is not known, it seems likely that the chiral A-oxide discriminates between the prochiral carbonyl cobalt units, either oxidizing one carbon monoxide selectively to produce a vacant site for the alkene insertion, or stabilizing a vacant site on one of the cobalts preferentially. This approach was modified by application of chiral precursor substrates [20]. Albeit the synthesis of the latter is cumbersome, the concept was successfully applied in several total syntheses, for example of hirsutene [21], brefeldine A [22], /9-cuparenone [23], and (+)-15-norpentalenene [24] (eq. (10)). Stoichiometric amounts of the mediator compound Co2(CO)8 are still necessary in this useful version of the Pauson-Khand reaction. 

As a result, the majority of contributions to the present edition have had to be either updated or completely replaced by new articles. This applies to the sections mentioned above, but also to the rapidly growing area of enantioselective synthesis (Sections 3.3.1 and 3.2.6), the catalytic hydrogenation of sulfur- and nitrogen-containing compounds in raw oils (Section 3.2.13), the Pauson-Khand reaction (Section 3.3.7), and a number of industrially relevant topics covered under Applied Homogeneous Catalysis in Part 2. New aspects of organometallic catalysis have emerged from the chemistry of renewable resources (Section 3.3.9) and the chemistry around the multi-talented catalyst methyltrioxorhenium (Section 3.3.13). 

Castro, J., Green, A. E., Moyano, A., Pericas, M. A., Poch, M., Riera, A., Sola, L., Verdaguer, X. Enantioselective Pauson-Khand reactions. 

Although the cobalt-mediated Pauson-Khand reaction was discovered more than 30 years ago, few asymmetric versions of this reaction have so far been developed. Up to now, the only direct method of controlling the enantioselectivity of intermo-lecular cobalt-mediated Pauson-Khand reactions involves the use of alkaloid N-oxides [59-62]. 

Another approach to the stoichiometric enantioselective Pauson-Khand reaction involves the use of chiral auxiliaries. Extensive investigations on this subject have been carried out by Periods, Moyano, Greene, and coworkers. Initial reports detailed the use of frans-2-phenylcyclohexanol as a chiral auxiliary for the... 

Substantial progress has also been made in the chiral auxiliary-based approach to an enantioselective intermolecular Pauson-Khand reaction. Initial studies utilizing alkynes substituted with fra s-2-phenylcyclohexanol produced cyclopentenones with low drs, however, the diastereomers were easily separable... 

Recently, the enantioselective Pauson-Khand reaction has been developed using chiral ligands.111 Hicks and Buchwald reported that, in the presence of (S,S)(EBTHI)Ti(CO)2, the asymmetric Pauson-Khand reaction of the 1,6-enyne 94 gave the bicyclic heterocycle 95 in a high yield with good enantiomeric excess (Scheme 32).lllab... 

Continuous, selective hydroformylation in supercritical CO2 using (acac)Rh(CO)2 immobilized on silica as catalyst shows certain advantages. A version of asymmetric hydroformylation in this medium has also been reported,. (Subcritical CO2 gas accelerates solventless synthesis involving solid reactants, including hydrogenation and hydroformylation.) The regioselective and enantioselective nickel-catalyzed hydrovinylation of styrenes in supercritical CO2 make 3-arylpropenes available in an optically active form. " Improvement in the performance of the Pauson-Khand reaction in supercritical media... 

Access to bicyclic enones from 1,6-enynes by the Pauson-Khand method is rendered enantioselective by installing a chiral t-butylsulfinyl group at C-1. Cyclization of a-benzylidene-aroylacetamides to furnish 3-arylindanones is subject to 1,5-asymmetric induction when the amide moiety is derived from a bulky 4-substitulted oxazolidin-2-one. Chiral ligands for the Pauson-Khand reaction have also been studied. Phosphine-borane (111) derived from (-l-)-pulegone is an example. 

Enantioselective versions of the Pauson-Khand reaction have been reported.3 8 Brucine-A-oxide promotes an asymmetric Pauson-Khand reaction, for example.3 9 enantiospecific variation has been reported by... 

Pauson-Khand reaction. The intramolecular annulation of enynes promoted by a chiral titanocene derivative 52 exhibits high degrees of enantioselectivity... 

Pauson-Khand reaction, An enantioselective synthesis of cyclopentenones... 

Other C-C bond-forming reactions have been successfully developed using SCCO2 and liquid CO2 as reaction media. Examples include the synthesis of cyclopentenones via cobalt-catalyzed cocyclizations of alkynes with alkenes and carbon monoxide (Pauson-Khand reaction) (Scheme 30) , enantioselective nickel-catalyzed hydrovinylation of styrenes (Scheme 31) , and the palladium-catalyzed hydroarylation of acyclic jS-substimted-o , j8-enones with aryl iodides (formal conjugate addition) (Scheme 32). ... 

Chapter 17 closes with a brief presentation of the Pauson-Khand reaction. The Pauson-Khand reaction (PKR) is a formal [2+2+1] cycloaddition reaction involving an alkyne, an alkene, and carbon monoxide to form a cyclopentanone shown generically in Equation 17.71. The Pauson-Khand reaction was initially reported as a stoichiometric reaction mediated by cobalt carbonyl, but it has been translated into a catalytic process in recent years. Most recently, it has developed into an enantioselective catalytic process. Complexes of Ti, Mo, W, Fe, Co, Ni, Ru, Rh, Ir, and Pd have all been shown to catalyze this reaction. 

Enines derived from allylic substitution products by propargylation offer many possibilities in organic synthesis. We have pursued Au-catalyzed cycloadditions with carbonyl compounds [31], enyne metathesis reactions in combination with Diels-Alder reactions [32], and a Pauson-Khand reaction as part of a synthesis of kainic acid [33]. The latter synthesis is described in Scheme 11.16 as a ret-rosynthetic scheme. The Ir-catalyzed allylic amination under in situ conditions proceeded with excellent enantioselectivity. Overall, our synthesis required 12 steps and gave a total yield of 12%. 

Rh2(CO)4Cl2/py catalyst (Capka, 1992a), and the Pauson-Khand reaction ofenynes catalyzed by sol-gel entrapped [Rh(cod)Cl]2 (Scheme 24-13). The latter process was carried out also in an enantioselective fashion (Park, 2003). 

In their report of crotylation reactions with cobalt carbonyl complexed aldehyde not only the enantioselectivity is improved, but it is also reversed. As can be seen in Scheme 3.47 the reaction of aldehyde 223 with the crotylation reagent 224 results in moderate enantioselectivities. If in contrast, cobalt complex 227 of the parent aldehyde 223 was used the opposite enantiomer was obtained, and in the latter case an improved selectivity was achieved. The double bond introduced via this crotylation is required for the intramolecular Pauson-Khand reaction that Roush and coworkers carried out [75]. 

Finally, Cramer and co-workers described an alternative route to classical Pauson-Khand reaction for the synthesis of cyclopentenones. The proposed procedure involves a reductive Ni -catalyzed [3+2] cycloaddition between aryl enoates and internal alkynes. More interestingly, the use of a chiral NHC led to a highly enantioselective reaction [eqn (10.38)]. Note that with unsymmetric alkynes the reaction is also regioselective. A plausible mechanism was proposed with the hypothesis that facial-selective coordination and incorporation of the enoate are controlled by a single chiral side chain of the carbene. 

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