Rhodium cyclopropanation

Enantioselective Cyclopropanation. Enantioselective versions of both copper and rhodium cyclopropanation catalysts are available. The copper-imine class of catalysts is enantioselective when chiral imines are used. Some of the chiral ligands that have been utilized in conjunction with copper salts are shown in Scheme 10.10. 

Some examples of catalytic cyclopropanation reactions with diazoacetamides are given in Table 14. In reactions with a-diazo-A,7V-dimethylacetamide catalyzed by tetraacetatodi-rhodium, cyclopropane yields decrease with decreasing alkene reactivity (ethoxyethene, 82% styrene, 47% cyclohexene, 21%). - Furthermore, with A-alkyl substituents larger than methyl, intramolecular carbenoid C-H insertion is in competition with alkene addition, e.g. formation of 4.i -259... 

Whereas the utility of these methods has been amply documented, they are limited in the structures they can provide because of their dependence on the diazoacetate functionality and its unique chemical properties. Transfer of a simple, unsubstituted methylene would allow access to a more general subset of chiral cyclopropanes. However, attempts to utilize simple diazo compounds, such as diazomethane, have never approached the high selectivities observed with the related diazoacetates (Scheme 3.2) [4]. Traditional strategies involving rhodium [3a,c], copper [ 3b, 5] and palladium have yet to provide a solution to this synthetic problem. The most promising results to date involve the use of zinc carbenoids albeit with selectivities less than those obtained using the diazoacetates. 

The catalyst exerts some influence on the bonds broken in hydrogenolysis of saturated cyclopropanes (775), but in vinyl and alkylidene cyclopropanes the effect is pronounced. Platinum or palladium are used frequently. In one case, Nishimura s [124a) catalyst, rhodium-platinum oxide (7 3), worked well where platinum oxide failed (.75). An impressive example of the marked influence of catalyst is the hydrogenation of the spirooctane 42, which,... 

Much of the early work into the rhodium(II)-catalysed formation of oxazoles from diazocarbonyl compounds was pioneered by the group of Helquist. They first reported, in 1986, the rhodium(II) acetate catalysed reaction of dimethyl diazomalonate with nitriles.<86TL5559, 93T5445, 960S(74)229> A range of nitriles was screened, including aromatic, alkyl and vinyl derivatives with unsaturated nitriles, cyclopropanation was found to be a competing reaction (Table 3). 

G. Rhodium Porphyrin Carbone Complexes and the Cyclopropanation of Alkenes Catalyzed by Rhodium Porphyrins... 

Both rhodium and osmium porphyrins are active for the cyclopropanation of alkenes. The higher activity of the rhodium porphyrin catalysts can possibly be attributed to a more reactive, cationic carbene intermediate, which so far has defied isolation. The neutral osmium carbene complexes are less active as catalysts but the mono- and bis-carbene complexes can be isolated as a result. 

Rhodium complexes with chelating bis(oxazoline) ligands have been described to a lesser extent for the cyclopropanation of olefins. For example, Bergman, Tilley et al. [32] have prepared a family of bis(oxazoline) complexes of coordinatively unsaturated monomeric rhodium(II) (see 20 in Scheme 13). Interestingly, the use of complex 20 in the cyclopropanation reaction of styrene afforded mainly the cis cyclopropane cis/trans = 63137), with 74% ee and not the thermodynamically favored trans isomer. No mechanistic suggestions are proposed by the authors to explain this unusual selectivity. 

Chelucci et al. [41] synthesized further chiral terpyridines derived from (-)-yd-pinene, (-i-)-camphor, and (-l-)-2-carene and tested their ability to chelate copper or rhodium for the asymmetric cyclopropanation of styrene. The copper catalysts were poorly efficient and selective in this reaction. The corresponding rhodium complexes led to the best result (64% ee) with the ligand derived from (-l-)-2-carene (ligand 33 in Scheme 17). 

In conclusion, many chiral pyridine-based ligands have been prepared from the chiral pool and have been successfully tested as ligands for the copper- or rhodium-catalyzed cyclopropanation of olefins. Alfhough efficient systems have been described, sometimes leading interestingly to the major cis isomer, the enantioselectivities usually remained lower than those obtained with the copper-bis(oxazoline) system. 

The above described experiments over atomically clean single crystal catalysts have been extended to studies of the kinetics of various catalytic reactions over chemically modified catalysts. Examples are recent studies Into the nature of poisoning by sulfur of the catalytic activity of nickel, ruthenium, and rhodium toward methana-tlon of CO (11,12) and CO2 (15). ethane (12) and cyclopropane (20) hydrogenolysls, and ethylene hydrogenation (21). 

Cyclopropanes 13 have been prepared from a NHC-rhodium catalysed decarbonylation of cyclobutanones 11 (Scheme 5.4) [6]. The isolated complex 12... 

In addition, this methodology was extended to the cyclopropanation of a series of alkenes with phenyldiazomethane, giving rise to the corresponding cyclopropanes with high yields, diastereo- and enantioselectivities, as shown in Scheme 6.9. It was shown that the diastereoselectivity of these reactions was not greatly altered by the type of rhodium carboxylate catalyst that was used. 

In 2004, a series of other chiral thioether-phosphine ligands based on a cyclopropane backbone were evaluated in the rhodium-catalysed hydrogenation of a dehydroamino acid by Molander el al As shown in Scheme 8.2, even if these ligands were generally active, only moderate enantioselectivities of up to 47% ee were obtained. 

Metal-Catalyzed. Cyclopropanation. Carbene addition reactions can be catalyzed by several transition metal complexes. Most of the synthetic work has been done using copper or rhodium complexes and we focus on these. The copper-catalyzed decomposition of diazo compounds is a useful reaction for formation of substituted cyclopropanes.188 The reaction has been carried out with several copper salts,189 and both Cu(I) and Cu(II) triflate are useful.190 Several Cu(II)salen complexes, such as the (V-f-butyl derivative, which is called Cu(TBS)2, have become popular catalysts.191... 

Several chiral ligands have been developed for use with the rhodium catalysts, among them are pyrrolidinones and imidazolidinones.207 For example, the lactamate of pyroglutamic acid gives enantioselective cyclopropanation reactions. 

Several of the copper and rhodium catalysts were compared in an intramolecular cyclopropanation.210 For the reaction leading to formation of a 10-membered ring, shown below, the copper catalysts gave higher enantioselectivity, but there were many subtleties, depending on ring size and other structural features in related systems. 

Aziridination of alkenes can be carried out using N-(p- to I ucncsu I I o n y I i m i n o) phenyliodinane and copper triflate or other copper salts.257 These reactions are mechanistically analogous to metal-catalyzed cyclopropanation. Rhodium acetate also acts as a catalyst.258 Other arenesulfonyliminoiodinanes can be used,259 as can chloroamine T260 and bromoamine T.261 The range of substituted alkenes that react includes acrylate esters.262... 

The Davies group has described several examples of a rhodium-catalyzed decomposition of a diazo-compound followed by a [2+1] cycloaddition to give divinyl cyclopropanes, which then can undergo a Cope rearrangement. Reaction of the pyrrol derivative 6/2-51 and the diazo compound 6/2-52 led to the tropane nucleus 6/2-54 via the cyclopropane derivative 6/2-53 (Scheme 6/2.11) [201]. Using (S)-lactate and (R)-pari lolaclorie as chiral auxiliaries at the diazo compound, a diastereoselectivity of around 90 10 could be achieved in both cases. 

The dominant role of copper catalysts has been challenged by the introduction of powerful group VIII metal catalysts. From a systematic screening, palladium(II) and rhodium(II) derivatives, especially the respective carboxylates62)63)64-, have emerged as catalysts of choice. In addition, rhodium and ruthenium carbonyl clusters, Rh COJjg 65> and Ru3(CO)12 e6), seem to work well. Tables 3 and 4 present a comparison of the efficiency of different catalysts in cyclopropanation reactions with ethyl diazoacetate under standardized conditions. 

Cu(OTf)2 generally gives yields intermediate between those of the other two catalysts, but with a closer resemblance to rhodium. In competition experiments, the better coordinating norbomene is preferred over styrene, just as in the case with Pd(OAc)2. Cu(acac)2, however, parallels Rh2(OAc)4 in its preference for styrene. These findings illustrate the variability of copper-promoted cyclopropanations, and it was suggested that in the Cu(OTf)2-catalyzed reactions of diazoesters, basic by-products, which are formed as the reaction proceeds, may gradually suppress... 

With the rhodium and copper catalysts, even the combination of equimolar amounts of olefin and diazoester will allow high yields of cyclopropanes if the addition rate is controlled meticulously (see Table 6 for examples). This circumstance is particularly useful for cyclopropanation of olefins which are in short supply. In combination with Rhg(CO)16, the easy recovery of the unchanged catalyst (by diluting the mixture with hexane and separating the precipitated catalyst from the liquid65 may render such a procedure particularly attractive from an economical point of view. 

All reactions listed in Tables 5-7 were carried out under a nitrogen atmosphere, but with the rhodium or palladium catalysts no noticeable or only minor reduction in cyclopropane yields was observed when air was present. In contrast, air clearly had a yield-diminishing effect in the CuCl P(0-/-Pr)3-catalyzed reactions, especially with cyclohexene and 3,4-dihydropyran. Cyclohexene was oxidized to 2-cyclohexen-l-one, and 3,4-dihydropyran gave 5,6-dihydro-4-pyrone and 5,6-dihydro-2-pyrone, albeit in yields below 8 % 59). 

Rhodium(II) pivalate has also been recommended for the cyclopropanation of vinyl halides with ethyl diazoacetate 78). As Table 8 shows, yields with this catalyst are far higher and reaction conditions milder than with copper. Failures are noted,... 

Table 8. Cyclopropanation of vinyl halides with ethyl diazoacetate in the presence of rhodium(Il) pivalate (Rhpiv) or copper...

The catalytic cyclopropanation of 1,3-dienes leads exclusively or nearly so to mono-cyclopropanation products, as long as no excess of diazocarbonyl compound is applied. The regioselectivity has been tested for representative rhodium, copper and palladium catalysts 59 7 ,72), and the results are displayed in Table 9. 

Cycloheptatriene, as an example of a conjugated triene, is mainly cyclopro-panated at an outer double bond (Scheme 6). This is true for Rh2(OAc)4, Cu(OTf)2 and Pd(OAc)2, but the highest yield is obtained again with the rhodium catalyst72>. Twofold cyclopropanation occurs to only a minor extent, as long as an excess of olefin is applied. With equal amounts of diazo ester and cycloheptatriene, double cyclopropanation increases and even traces of the triply cyelopropanated triene are found with Rh2(OAc)4 and Cu(OTf)2. This behavior essentially parallels the earlier... 

Cyclopropanation of C=C bonds by carbenoids derived from diazoesters usually occurs stereospeciflcally with respect to the configuration of the olefin. This has been confirmed for cyclopropanation with copper 2S,S7,60 85), palladium 86), and rhodium catalysts S9,87>. However, cyclopropanation of c -D2-styrene with ethyl diazoacetate in the presence of a (l,2-dioximato)cobalt(II) complex occurs with considerable geometrical isomerization88). Furthermore, CuCl-catalyzed cyclopropanation of cis-2-butene with co-diazoacetophenone gives a mixture of the cis- and trans-1,2-dimethylcyclopropanes 89). 

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