Cyclopropanes Diazo acetate

Interaction of furans with vinylcarbenes, derived from diazo acetates 732, presumably proceeds via cyclopropanation of the furan double bond... 

The reverse trend was found for intramolecular cyclopropanation of a-(alkenyloxysilyl)diazo-acetic esters. For the synthesis of methyl 2,2-diisopropyl-3-oxa-2-silabicyclo[4.1.0]heptane-l-carboxylate (7) from methyl diazo[(but-3-enyloxy)diisopropylsilyl]acetate, the thermal procedure gave the best result. In contrast, the lower homologs, 3-oxo-2-silabicyclo[3.1.0]hexanes, were only obtained by photochemical or catalytic decomposition of the corresponding diazo esters (see also Section 1.2.1.10.). 

Copper powder, copper bronze, Cu O, CuO, CuSO, CuCl and CuBr were the first catalysts which were used routinely for cyclopropanation of olefins as well as of aromatic and heteroaromatic compounds with diazoketones and diazoacetates. Competing insertion of a ketocarbene unit into a C—H bond of the substrate or solvent remained an excpetion in contrast to the much more frequent intramolecular C—H insertion reactions of appropriately substituted a-diazoketones or diazoacetates Reviews dealing with the cyclopropanation chemistry of diazo-acetic esters (including consideration of the efficiency of the copper catalysts mentioned above) and diazomalonic esters as well as with intramolecular cyclopropanation reactions of diazoketones have appeared. 

Similarly, significant improvements with methallyl and ( -butyl)allyl diazoacetates can be achieved by switching catalysts from Rh2(MEPY)4 to Rh2(MP-PIM)4. Allyl diazo esters other than diazo acetates have not yet been examined in detail. Encouragingly, Doyle s group [41] have found that high levels of enantio-control in intramolecular cyclopropanation can be realized with allyl diazopropionates and the Rh2(4S-MEOX)4 catalyst, Eq. (25). 

In 1978, Nakamura and coworkers studied the decomposition of the carbe-noid prepared from ethyl diazoacetate and various palladium complexes [53]. They have found that the use of several chiral hgands did not induce any appreciable enantioselectivity when the cyclopropanation was carried out with ethyl diazo acetate and styrene. From these observations, it was postulated that the chiral ligand did not seem to be tightly bound to the active catalytic species. 

Cyclopropanation reactions with these catalysts are typically carried out with 0.5-2 mol% (with respect to the diazo compound) of catalyst and a five- to tenfold excess of alkene. Under these conditions, the formation of formal carbene dimers [e.g. diethyl ( )-but-2-enedioate and (Z)-but-2-enedioate from ethyl diazo acetate], arising from the competition between alkene and the metal-carbene intermediate for the diazo compound, can be largely suppressed. It has been shown, however, that the control of the addition rate of the diazoacetic ester has no effect on the cyclopropane yield with (dibenzonitrile)palladium(II) chloride as catalyst, in contrast to tetraacetatodirhodium, Rh6(CO)16, and CuCl P(OR)3.152... 

The rhodium- or copper-catalyzed cyclopropanation of furan and its derivatives with diazo-acetic esters,300-302 or ethyl 2-diazopropanoate300 usually leads to a mixture of the 2-oxa-bicyclo[3.1.0]hex-3-ene-e co-6-carboxylate, ring-opened (4Z)-6-oxohexa-2,4-dienoates, and ring-substituted furans. Only with electron-deficient furans methyl furan-2-carboxylates, 2-[( )-2-methoxycarbonylvinyl]furan300 and with benzofuran,301,303 was the cyclopropane product obtained exclusively. Examples 37-40 are representative.300... 

Decomposition using catalytic CuOTf, however, gave products 68 and 69 resulting from intramolecular cyclopropanation in excellent yields (eq 15). Similarly, [(3-butenyl)oxysilyl]diazo-acetate 73 underwent intramolecular cyclopropanation to give silabicyclohexane system 74 under thermal conditions in 58% yield (eq 17). ... 

The majority of preparative methods which have been used for obtaining cyclopropane derivatives involve carbene addition to an olefmic bond, if acetylenes are used in the reaction, cyclopropenes are obtained. Heteroatom-substituted or vinyl cydopropanes come from alkenyl bromides or enol acetates (A. de Meijere, 1979 E. J. Corey, 1975 B E. Wenkert, 1970 A). The carbenes needed for cyclopropane syntheses can be obtained in situ by a-elimination of hydrogen halides with strong bases (R. Kdstcr, 1971 E.J. Corey, 1975 B), by copper catalyzed decomposition of diazo compounds (E. Wenkert, 1970 A S.D. Burke, 1979 N.J. Turro, 1966), or by reductive elimination of iodine from gem-diiodides (J. Nishimura, 1969 D. Wen-disch, 1971 J.M. Denis, 1972 H.E. Simmons, 1973 C. Girard, 1974),... 

The comparison between the cycloaddition behavior of simple diazoketones and of ethyl diazopyruvate 56 towards the same olefin underlines the crucial influence of the ethoxycarbonyl group attached to the carbonyl function. This becomes once again evident when COOEt is replaced by an acetal function, such as in l-diazo-3,3-di-methoxy-2-butanone 86 with enol ethers and acetates, cyclopropanes rather than dihydrofurans are now obtained 113). ... 

The catalytic activity of rhodium diacetate compounds in the decomposition of diazo compounds was discovered by Teyssie in 1973 [12] for a reaction of ethyl diazoacetate with water, alcohols, and weak acids to give the carbene inserted alcohol, ether, or ester product. This was soon followed by cyclopropanation. Rhodium(II) acetates form stable dimeric complexes containing four bridging carboxylates and a rhodium-rhodium bond (Figure 17.8). 

Rhodium-catalyzed diazo insertions, known since 1976, have been extensively reviewed39. The first report40 indicated that rhodium acetate efficiently catalyzes diazo insertion into an alkene, giving the cyclopropane. Rhodium-catalyzed intramolecular C-H insertion was first observed by workers at Beecham Pharmaceuticals, who reported that 1, on exposure to a catalytic amount of rhodium acetate, cyclizes cleanly to the /1-lactam41. This approach to thienamycin derivatives has been developed further by these workers42,43. 

Intermolecular cyclopropanation of diazoketones is an effective method in organic synthesis. Wenkert and coworkers have applied this methodology to the synthesis of a substantial number of cyclopropane adducts 2868, 2969 and 307° which are synthetic intermediates in the preparation of natural products (equations 41—43). Copper catalysts were chosen for these transformations. Another interesting application of intermolecular cyclopropanation is to be found in Daniewski s total synthesis of an aromatic steroid. Palladium(II) acetate catalysed decomposition of 4-bromo-l-diazo-2-butanone in the presence of m-methoxystyrene was used to give the cyclopropyl ketone 31 which was a key intermediate in the total synthesis (equation 44)71. 

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. 

Bicyclobutanes are also obtained from the catalytic decomposition of diazo compound 17492 (equation 51). Copper(I) iodide was the catalyst of choice, whereas rhodium(II) acetate did not show any activity in this case. When the related diazo compound 175 was decomposed, the product pattern depended in an unusually selective manner on the catalyst92. Intramolecular cyclopropanation leading to 176 is obviously less favorable than for carbene 172 and must yield to the 1,2-hydride shift not observed with the former carbene. The configuration of the resulting butadiene 177 can be completely reversed by the choice of the catalyst. 

Intramolecular cycloaddition of a diazo ketone to a cyclopropene. Rhodium) II) acetate is markedly superior to copper or copper(II) sulfate as the catalyst for cyclopropanation of l,4-diacetoxy-2-butyne with /-butyl diazoacetatc. The product (1) was converted by known steps into the diazo ketone 2. In the presence of rhodium(II) acetate, 2 undergoes intramolecular cycloaddition to the cyclopropene double bond to give the highly strained tricyclic pentanone derivative 3 in 30% yield. C oppcr catalysts are less efficient for this conversion. 

Enol ethers react with diazo ketones in the presence of Cu-catalysts to give cyclopropanes such as 24. Ring cleavage with acid and subsequent intramolecular aldol condensation constitutes a flexible route to cyclopentenones (Eq. 7) 12-13). This procedure has also been applied to a synthesis of cis-jasmone employing isopropenyl acetate as a donor olefin 14). 

The enol acetate moiety in diketene can be utilized for cyclopropane formation. Unfortunately, with most diazo compounds, yields are rather moderate 29), and therefore the synthetic value of methods developed on this basis is restricted. As exemplified by the ethyl diazoacetate adduct 44 (Scheme 4) the ring opening of this masked tricarbonyl compound can lead to different classes of acyclic or cyclic products. The outcome of these reactions depends on the conditions employed. They simultaneously transform the P-ketoester unit present in 44 29b). 

Reactions of trimethylsilyl enol ethers with diazo ketones give cyclopropanes contaminated by ring opened compounds 60,61). Use of the more stable tert-BuMe2Si-derivatives or of Rh2 (0Ac)4 as a catalyst might eventually improve the situation. O-Silylated ketene acetals and O.S-ketene acetals, respectively, did not provide products with cyclopropane structure 61 ... 

In contrast to the carbene and carbenoid chemistry of simple diazoacetic esters, that of a-silyl-a-diazoacetic esters has not yet been developed systematically [1]. Irradiation of ethyl diazo(trimethylsilyl)acetate in an alcohol affords products derived from 0-H insertion of the carbene intermediate, Wolff rearrangement, and carbene- silene rearrangement [2]. In contrast, photolysis of ethyl diazo(pentamethyldisilanyl)acetate in an inert solvent yields exclusively a ketene derived from a carbene->silene->ketene rearrangement [3], Photochemically generated ethoxycarbonyltrimethyl-silylcarbene cyclopropanates alkenes and undergoes insertion into aliphatic C-H bonds [4]. Copper-catalyzed and photochemically induced cyclopropenation of an alkyne with methyl diazo(trimethylsilyl)acetate has also been reported [5]. 

Scheme 6. Cyclopropanation of monosubstituted alkenes with methyl diazo(trialkylsiIyl)acetates...

An intramolecular carbenoid addition onto a carbon-carbon double bond provides a possible synthetic route to the pyrrolidine ring. The rho-dium(II) acetate-catalyzed reaction of diazo amide 106 leads to a mixture of diastereomers 107 and 108 (6 1) in 43% yield (88TL1181). The decomposition of AjA-diallyl-a-diazoacetamide catalyzed by Rh2(55-MEPY)4 forms product 109 from an enantioselective intramolecular cyclopropanation (50% yield, 72% e.e.) (94T1665). Spiro-fused ring systems were produced by this route from quinonediazides 110 and 111 under irradiation (83TL4773 86TL2687). 

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