Cyclopropanation, rhodium-carbene transfer

Catalytic asymmetric cyclopropanations via carbene transfer to alkenes were reviewed by Singh and co-workers in 1997," Doyle and Protopopova in 1998," and mostly recently by Doyle in 2000." The reaction can be catalyzed by copper," rhodium," and other metals." Bis(oxazolines) are known to be among the most effective ligands for this cyclopropanation reaction (see Chapter 9). 

The q1-coordinated carbene complexes 421 (R = Ph)411 and 422412) are rather stable thermally. As metal-free product of thermal decomposition [421 (R = Ph) 110 °C, 422 PPh3, 105 °C], one finds the formal carbene dimer, tetraphenylethylene, in both cases. Carbene transfer from 422 onto 1,1-diphenylethylene does not occur, however. Among all isolated carbene complexes, 422 may be considered the only connecting link between stoichiometric diazoalkane reactions and catalytic decomposition [except for the somewhat different results with rhodium(III) porphyrins, see above] 422 is obtained from diazodiphenylmethane and [Rh(CO)2Cl]2, which is also known to be an efficient catalyst for cyclopropanation and S-ylide formation with diazoesters 66). 

Rhodium(II) carboxylate dimers and their carboxamide counterparts have been demonstrated to be exceptionally useful catalysts for carbene transfer processes involving diazocarbonyl substrates [1]. Doyle s seminal work identified Rh2(OAc)4 as the catalyst of choice for a variety of cyclopropanation, C-H insertion, and ylide rearrangement transformations using diazoketones or diazoesters [2]. Important contributions by Taber [3], Padwa [4], and Davies [5] further established the superior catalytic activity of dirho-dium catalysts and the excellent selectivity of rhodium-[Pg.417]

The ligand was then used to form a variety of transition metal carbene complexes [207] (see Figure 3.72). Interestingly, more than one method for the formation of transition metal carbene complexes was successfully employed presence of an inorganic base (IC COj) to deprotonate the imidazolium salt and the silver(I) oxide method with subsequent carbene transfer to rhodium(I), iridium(I) and copperfi), respectively. The silver(I) and copper(I) carbene complexes were used for the cyclopropanation of styrene and indene with 1,1-ethanediol diacetate (EDA) giving very poor conversion with silver (< 5%) and qnantitative yields with copper. The diastereomeric ratio (endolexo) was more favonrable with silver than with copper giving almost a pnre diastereomer for the silver catalysed reaction of indene. 

In contrast to the wealth of chemistry reported for catalyzed reactions of diazocarbonyl compounds, there are fewer applications of diazomethane as a carbenoid precursor. Catalytic decomposition of diazomethane, CH2N2, has been reported as a general method for the methylenation of chemical compounds [12]. The efficacy of rhodium catalysts for mediating carbene transfer from diazoalkanes is poor. The preparative use of diazomethane in the synthesis of cyclopropane derivatives from olefins is mostly associated with the employment of palladium cat-... 

As already mentioned for rhodium carbene complexes, proof of the existence of electrophilic metal carbenoids relies on indirect evidence, and insight into the nature of intermediates is obtained mostly through reactivity-selectivity relationships and/or comparison with stable Fischer-type metal carbene complexes. A particularly puzzling point is the relevance of metallacyclobutanes as intermediates in cyclopropane formation. The subject is still a matter of debate in the literature. Even if some metallacyclobutanes have been shown to yield cyclopropanes by reductive elimination [15], the intermediacy of metallacyclobutanes in carbene transfer reactions is in most cases borne out neither by direct observation nor by clear-cut mechanistic studies and such a reaction pathway is probably not a general one. Formation of a metallacyclobu-tane requires coordination both of the olefin and of the carbene to the metal center. In many cases, all available evidence points to direct reaction of the metal carbenes with alkenes without prior olefin coordination. Further, it has been proposed that, at least in the context of rhodium carbenoid insertions into C-H bonds, partial release of free carbenes from metal carbene complexes occurs [16]. Of course this does not exclude the possibility that metallacyclobutanes play a pivotal role in some catalyst systems, especially in copper-and palladium-catalyzed reactions. 

The catalytic activity of low-valent ruthenium species in carbene-transfer reactions is only beginning to emerge. The ruthenium(O) cluster RujCCO), catalyzed formation of ethyl 2-butyloxycyclopropane-l-carboxylate from ethyl diazoacetate and butyl vinyl ether (65 °C, excess of alkene, 0.5 mol% of catalyst yield 65%), but seems not to have been further utilized. The ruthenacarborane clusters 6 and 7 as well as the polymeric diacetatotetracarbonyl-diruthenium (8) have catalytic activity comparable to that of rhodium(II) carboxylates for the cyclopropanation of simple alkenes, cycloalkenes, 1,3-dienes, enol ethers, and styrene with diazoacetic esters. Catalyst 8 also proved exceptionally suitable for the cyclopropanation using a-diazo-a-trialkylsilylacetic esters. ... 

The ability of chiral bis(camphorquinone-a-dioximato)cobalt(Il) complexes (Section 1.2.1.2.4.2.6.3.1.) to catalyze carbene transfer from diazocarbonyl compounds (diazoacetic esters, 2-diazo-l-phenylethan-l-one) to terminal alkenes conjugated with vinyl, aryl, carbonyl, and cyano groups, has already been mentioned. The ee-values are 75-88 /o at best, often lower. The highest values are again obtained with bulky diazoacetic esters. The significance of these catalysts, however, is their ability to promote cyclopropanation of electron-deficient alkenes, such as acrylates and acrylonitriles, in contrast to the rhodium and copper catalysts discussed above. 

Photochemical decomposition of diazo(trimethylsilyl)methane (1) in the presence of alkenes has not been thoroughly investigated (see Houben-Weyl Vol. E19b, p 1415). The available experimental data [trimethylsilylcyclopropane (17% yield) and la,2a,3j8-2,3-dimethyl-l-trimethylsilylcyclopropane (23% yield)] indicate that cyclopropanation occurs only in low yield with ethene and ( )-but-2-ene. In both cases the formal carbene dimer is the main product. In reactions with other alkenes, such as 2,3-dimethylbut-2-ene, tetrafluoroethene or hexafluoro-propene, no cyclopropanes could be detected.The transition-metal-catalyzed decomposition of diazo(trimethylsilyl)methane (1) has been applied to the synthesis of many different silicon-substituted cyclopropanes (see Table 3 and Houben-Weyl Vol.E19b, p 1415) 3.20a,b,2i.25 ( iQp. per(I) chloride has been most commonly used for carbene transfer to ethyl-substituted alkenes, cycloalkenes, styrene, and related arylalkenes. For the cyclopropanation of acyl-substituted alkenes, palladium(II) chloride is the catalyst of choice, while palladium(II) acetate was less efficient, and copper(I) chloride, copper(II) sulfate and rhodium(II) acetate dimer were totally unproductive. The cyclopropanation of ( )-but-2-ene represents a unique... 

A dirhodium tetracarboxylate complex coordinated by two bromocalix[4]arene macrocycles exhibited two toluene molecules coordinated to the rhodium centers and inserted in the clefts, which are formed by the vicinal -bromophenyl rings of the two calixarene units (Figure 29). This complex has been found to be an efficient catalyst for two carbene transfer reactions, alkene cyclopropanation, and intramolecular C-H insertion, in terms of stereo- and regioselectivity. 

The cyclopropanation of alkenes via carbene transfer from diazo compounds can be achieved by a variety of transition metals. The most popular catalysts for this transformation are based on copper(I) and rhodium(II) complexes, however, paUadium(II) has been shown, as demonstrated first by Kirmse and Kapps, "- to be effective and even superior for certain substrates and reagents. " ... 

Examples involving osmium [168,169] and iron [170] porphyrins as catalysts have also been reported but the catalysts mainly provide a trans product. A mechanism for iron porphyrin-catalyzed cyclopropanation was proposed by Kodadek and coworkers [170]. A transition state for carbene transfer which is reached later than in the rhodium porphyrin catalyzed reaction is suggested. In this case, the olefin is parallel to the metallocarbene and significant bonding has occurred. This geometry explains why 1,2 disubstituted alkenes are poor substrates since there is a steric interaction between the porphyrin ring and the alkene [170]. 

Synthesis of the chiral catalysts to introduce enantioselectivity in carbene transfer reactions is a subject of great interest. Often copper and rhodium chiral catalysts are of choice for the carbene transfer reactions. In some reports, immobilized chiral dirhodium (II) catalyst were employed successfully in asymmetric cyclopropanation reactions. Ubeda and coworkers reported the immobilization of chiral Rh2(02CR)2(PC)2 (PC = ort/io-metalated phosphine) compounds on cross-linked polystyrene (PS) resin by an... 

Cyclopropanation of olefins is currently performed by direct transition metal-catalyzed carbene transfer from a diazo compound to the olefin. Dirhodium(II) carboxylates and carboxamidates have proved to be the catalysts of choice. Other rhodium compounds, such as Rh (CO),6, Rh2(BF4)4, and rhodium(III) porphyrins, have been also investigated, but did not show better reactivity, while rhodium(I) compounds have never been successful [66]. Other complexes containing copper or ruthenium have been tested in cyclopropanation reactions, but have never shown better reactivity or selectivity than rhodinm(II) compounds [67]. 

Reactions of rhodium porphyrins with diazo esters - According to Callot et al., iodorhodium(III) porphyrins are efficient catalysts for the cyclopropanation of alkenes by diazo esters [320,321], The transfer of ethoxycarbonylcarbene to a variety of olefins was found to proceed with a large syn-selectivity as compared with other catalysts. In their study to further develop this reaction to a shape-selective and asymmetric process [322], Kodadek et al. [323] have delineated the reaction sequences (29, 30) and identified as the active catalyst the iodoalkyl-rhodium(III) complex resulting from attack of a metal carbene moiety Rh(CHCOOEt) by iodide. 

Several iodonium ylides, thermally or photochemically, transferred their carbene moiety to alkenes which were converted into cyclopropane derivatives. The thermal decomposition of ylides was usually catalysed by copper or rhodium salts and was most efficient in intramolecular cyclopropanation. Reactions of PhI=C(C02Me)2 with styrenes, allylbenzene and phenylacetylene have established the intermediacy of carbenes in the presence of a chiral catalyst, intramolecular cyclopropanation resulted in the preparation of a product in 67% enantiomeric excess [12]. 

The direct transfer of carbene from diazocompounds to olefins catalyzed by transition metals is the most straightforward synthesis of cyclopropanes [3,4]. Reactions of diazoesters with olefins have been studied using complexes of several transition metals as catalysts. In most cases trans-isomers are preferably obtained, but the selectivity depends on the nature of the complex. In general the highest trans-selectivity is obtained with copper catalysts and it is reduced with palladium and rhodium complexes. Therefore, the rhodium mesotetraphenylporphyrin (RhTPPI) [5] and [(r 5-C5H5)Fe(CO)2(THF)]BF4 [6] are the only catalysts leading to a preference for the cis-isomer in the reaction of ethyl diazoacetate with styrene. 

Addition of carbenoids derived from a-diazo carbonyl compounds to prostereogenic olefins can furnish two diastereomeric cyclopropane derivatives (dsjtrans- or euefo/exo-isomers). The metal-catalyzed transfer of alkoxycarbonyl carbenes has been closely investigated it usually furnishes the mwv-substituted cyclopropanes with moderate to good preference. The rhodium(II/-catalyzed reaction of ethyl diazoacetate with various olefins typically demonstrates that the d.r. (trans/cis) increases when the substituent on the olefin becomes sterically more demanding5. 

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