Copper catalysts alkenes

It has been pointed out earlier that the anti/syn ratio of ethyl bicyclo[4.1,0]heptane-7-carboxylate, which arises from cyclohexene and ethyl diazoacetate, in the presence of Cul P(OMe)3 depends on the concentration of the catalyst57). Doyle reported, however, that for most combinations of alkene and catalyst (see Tables 2 and 7) neither concentration of the catalyst (G.5-4.0 mol- %) nor the rate of addition of the diazo ester nor the molar ratio of olefin to diazo ester affected the stereoselectivity. Thus, cyclopropanation of cyclohexene in the presence of copper catalysts seems to be a particular case, and it has been stated that the most appreciable variations of the anti/syn ratio occur in the presence of air, when allylic oxidation of cyclohexene becomes a competing process S9). As the yields for cyclohexene cyclopropanation with copper catalysts [except Cu(OTf)2] are low (Table 2), such variations in stereoselectivity are not very significant in terms of absolute yields anyway. 

In order to rationalize the catalyst-dependent selectivity of cyclopropanation reaction with respect to the alkene, the ability of a transition metal for olefin coordination has been considered to be a key factor (see Sect. 2.2.1 and 2.2.2). It was proposed that palladium and certain copper catalysts promote cyclopropanation through intramolecular carbene transfer from a metal carbene to an alkene molecule coordinated to the same metal atom25,64. The preferential cyclopropanation of terminal olefins and the less hindered double bond in dienes spoke in favor of metal-olefin coordination. Furthermore, stable and metastable metal-carbene-olefin complexes are known, some of which undergo intramolecular cyclopropane formation, e.g. 426 - 427 415). 

Evans suggests that the catalyst resting state in this reaction is a 55c Cu alkene complex 58, Scheme 4 (35). Variable temperature NMR studies indicate that the catalyst complexes one equivalent of styrene which, in the presence of excess alkene, undergoes ready alkene exchange at ambient temperature but forms only a mono alkene-copper complex at -53°C. Addition of diazoester fails to provide an observable complex. These workers invoke the metallacyclobutane intermediate 60 via a formal [2 + 2] cycloaddition from copper carbenoid alkene complex 59. Formation of 60 is the stereochemistry-determining event in this reaction. The square-planar S Cu(III) intermediate 60 then undergoes a reductive elimination forming the cyclopropane product and Complex 55c-Cu, which binds another alkene molecule. 

The first catalytic, asymmetric aziridination of an alkene in good yield and high enantioselectivity was recently reported56. Thus styrene (63) was treated with [N-(p-toluenesulphonyl)imino]phenyliodinane (64) and an asymmetric copper catalyst to yield (/ )-Ar-(p-toluenesulphonyl)-2-phenylaziridine [(/ )-65] in 97% yield with an ee of 61%, the catalyst being the complex formed in situ in chloroform from the chiral bis[(5 ) 4-ferf-butyloxazoline] [(S,S)-66] and copper triflate (CuOTf)56, the reaction proceeding by way of a nitrene transfer57. 

There are no mechanistic details known from intermediates of copper, like we have seen in the studies on metathesis, where both metal alkylidene complexes and metallacyclobutanes that are active catalysts have been isolated and characterised. The copper catalyst must fulfil two roles, first it must decompose the diazo compound in the carbene and dinitrogen and secondly it must transfer the carbene fragment to an alkene. Copper carbene species, if involved, must be rather unstable, but yet in view of the enantioselective effect of the ligands on copper, clearly the carbene fragment must be coordinated to copper. It is generally believed that the copper carbene complex is rather a copper carbenoid complex, as the highly reactive species has reactivities very similar to free carbenes. It has not the character of a metal-alkylidene complex that we have encountered on the left-hand-side of the periodic table in metathesis (Chapter 16). Carbene-copper species have been observed in situ (in a neutral copper species containing an iminophosphanamide as the anion), but they are still very rare [9],... 

Bobianko and Gorokhovatskil 152) and Roiter, Golodets, and Pyatnit-skii 153) found correlations between the rates of the total oxidation of alkenes and alkanes on copper catalysts and the strength of the C—C bond, which is ruptured in the rate-determining step (series 137, six reactants series 138, seven reactants). 

Carbenoids derived from the aryldiazoacetates are excellent donor/acceptor systems for the asymmetric cyclopropanation reaction [22]. Methyl phenyldiazoacetate 3 cyclopropanation of monosubstituted alkenes catalyzed by Rh2(S-DOSP)4 is highly diaster-eo- and enantioselective (Tab. 14.5) [22]. Higher enantioselectivities can be obtained when these reactions are performed at -78°C, as the catalyst maintains high solubility and activity at this temperature. The phenyldiazoacetate system has been evaluated using many popular rhodium(II) and copper catalysts the rhodium(ll) prolinates have proven to be superior catalysts for this class of carbenoids [37, 38]. 

In contrast to the intermolecular cyclopropanation, the dirhodium tetraprolinates give modest enantioselectivities for the corresponding intramolecular reactions with the do-nor/acceptor carbenoids [68]. For example, the Rh2(S-DOSP)4-catalyzed reaction with al-lyl vinyldiazoacetate 32 gives the fused cyclopropane 33 in 72% yield with 72% enantiomeric excess (Eq. 4) [68]. The level of asymmetric induction is dependent upon the substitution pattern of the alkene cis-alkenes and internally substituted alkenes afford the highest asymmetric induction. Other rhodium and copper catalysts have been evaluated for reactions with vinyldiazoacetates, but very few have found broad utility [42]. 

Certain acyclic diazoketones react with electron-rich alkenes (such as enol ethers) to form dihydrofurans. The catalyst of choice is Rh2(OAc)4 for these and related transformations, although copper catalysts have been used as well. A variety of ot-diazoketones and ot-diazoaldehydes can be used, including PhCOCHN2, NjCHCOCOOEt, MeCOC(N2)COMe, and MeCOC(N2)COOR (345,346). Wenkert (347) and Alonso (348) studied the scope of this dihydrofuran synthesis [Scheme 8.75 e.g., 304 305 R = H (349), COOEt (350)]. 

In intramolecular cyclopropanation, Doyle s catalysts (159) show outstanding capabilities for enantiocontrol in the cyclization of allyl and homoallyl diazoesters to bicyclic y-and <5-lactones, respectively (equations 137 and 138)198 205. The data also reveal that intramolecular cyclopropanation of Z-alkenes is generally more enantioselective than that of E-alkenes in bicyclic y-lactone formation198. Both Rh(II)-MEPY enantiomers are available and, through their use, enantiomeric products are accessible. In a few selected cases, the Pfaltz catalyst 156 also results in high-level enandoselectivity in intramolecular cyclopropanation (equation 139)194. On the other hand, the Aratani catalyst is less effective than the Doyle catalyst (159) or Pfaltz catalyst (156) in asymmetric intramolecular cyclo-propanations201. In addition, the bis-oxazoline-derived copper catalyst 157b shows lower enantioselectivity in the intramolecular cyclopropanation of allyl diazomalonate (equation 140)206. 

The rhodium(II) catalysts and the chelated copper catalysts are considered to coordinate only to the carbenoid, while copper triflate and tetrafluoioborate coordinate to both the carbenoid and alkene and thus enhance cyclopropanation reactions through a template effect.14 Palladium-based catalysts, such as palladium(II) acetate and bis(benzonitrile)palladium(II) chloride,l6e are also believed to be able to coordinate with the alkene. Some chiral complexes based on cobalt have also been developed,21 but these have not been extensively used. 

Rhodium(II) acetate appears to be the most generally effective catalyst, and most of this discussion will center around the use of this catalyst with occasional reference to other catalysts when significant synthetic advantages can be gained. Cyclopropanation of a wide range of alkenes is possible with alkyl diazoacetate, as is indicated with the examples shown in Table l.l6e>37 The main limitations are that the alkene must be electron rich and not too sterically crowded. Poor results were obtained with trans-alkenes. Comparison studies have been carried out with copper and palladium catalysts and commonly the yields were lower than with rhodium catalysts. Cyclopropanation of styrenes and strained alkenes, however, proceeded extremely well with palladium(ll) acetate, while copper catalysts are still often used for cyclopropanation of vinyl ethers.38-40... 

The cyclopropanation of alkenes, alkynes, and aromatic compounds by carbenoids generated in the metal-catalyzed decomposition of diazo ketones has found widespread use as a method for carbon-carbon bond construction for many years, and intramolecular applications of these reactions have provided a useful cyclization strategy. Historically, copper metal, cuprous chloride, cupric sulfate, and other copper salts were used most commonly as catalysts for such reactions however, the superior catalytic activity of rhodium(ll) acetate dimer has recently become well-established.3 This commercially available rhodium salt exhibits high catalytic activity for the decomposition of diazo ketones even at very low catalyst substrate ratios (< 1%) and is less capricious than the old copper catalysts. We recommend the use of rhodium(ll) acetate dimer in preference to copper catalysts in all diazo ketone decomposition reactions. The present synthesis describes a typical cyclization procedure. 

TABLE 5.5. Enantioselective Cyclopropanation of Alkenes with Diazo Esters using Bis-oxazoline Copper Catalysts... 

Enantiocontrol with 21-23 is lower than that achieved with chiral copper catalysts for reactions of diazoacetates with styrene and a few other alkenes examined thus far [68], but the carboxamidates display far greater stereocontrol than do the dirhodium(II) carboxylates for the same reactions [69]. However, Hashimoto has reported the use of chiral piperidinonate 24 and found exceptional enantiocontrol in the cyclopropanation of styrene and both mono- and... 

Terminal alkenes can be selectively oxidized to aldehydes by reaction with oxygen, using a palladium-copper catalyst in tertiary butanol (equation 35)160. This reaction is contrary to the normal oxidation process which yields a ketone as the major product. The palladium(II) oxidation of terminal alkenes to give methyl ketones is known as the Wacker process. It is a very well established reaction in both laboratory and industrial synthesis161162. The Wacker oxidation of alkenes has been used in the key step in the synthesis of the male sex pheromone of Hylotrupes bajulus (equation 36)163. 

More recently, Pfaltz has reported high enantioselectivities for the cyclopropanation of monosubstituted alkenes and dienes with diazo carbonyl compounds using chiral (semicorrinato)copper complexes (P-Cu) (23-25), and Evans, Masamune, and Pfaltz subsequently discovered exceptional enantioselectivities in intermolecular cyclopropanation reactions with the analogous bis-oxazoline copper complexes (26-28). With the exception of the chiral (camphorquinone dioximato)cobalt(II) catalysts (N-Co) reported by Nakamura and coworkers (29,30), whose reactivities and selectivities differ considerably from copper catalysts, chiral complexes of metals other than copper have not exhibited similar promise for high optical yields in cyclopropanation reactions (37). 

The reaction of elemental silicon with a gaseous mixture of hydrogen chloride and unsaturated hydrocarbons such as alkenes (e.g., ethylene and propylene) and alkyne such as acetylene in the presence of copper catalyst also affords the corresponding organodichlorosilanes. 

Enantioselective Aziridination of Alkenes. Copper complexes with neutral methylenebis(oxazoline) ligands (1) and (2) have also been employed as enantioselective catalysts for the reaction of alkenes with (Al-tosylimino)phenyliodinane, leading to A-tosylaziridines. The best results have been reported for cinna-mate esters as substrates, using 5 mol % of catalyst prepared from CuOTf and the phenyl-substituted ligand (2) (eq 6). The highest enantiomeric excesses are obtained in benzene, whereas in more polar and Lewis basic solvents, such as acetonitrile, the selectiv-ities are markedly lower. The chemical yield can be substantially improved by addition of 4X molecular sieves. Both Cu - and Cu"-bisoxazoline complexes, prepared from Cu or Cu triflate, respectively, are active catalysts, giving similar results. In contrast to the Cu-catalyzed cyclopropanation reactions discussed above, in which only Cu complexes are catalytically active, here Cu complexes are postulated as the actual catalysts. ... 

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