Diazo-acetic ester compounds

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. 

The diazo function in compound 4 can be regarded as a latent carbene. Transition metal catalyzed decomposition of a diazo keto ester, such as 4, could conceivably lead to the formation of an electron-deficient carbene (see intermediate 3) which could then insert into the proximal N-H bond. If successful, this attractive transition metal induced ring closure would accomplish the formation of the targeted carbapenem bicyclic nucleus. Support for this idea came from a model study12 in which the Merck group found that rhodi-um(n) acetate is particularly well suited as a catalyst for the carbe-noid-mediated cyclization of a diazo azetidinone closely related to 4. Indeed, when a solution of intermediate 4 in either benzene or toluene is heated to 80 °C in the presence of a catalytic amount of rhodium(n) acetate (substrate catalyst, ca. 1000 1), the processes... 

Under the conditions of homogeneous catalysis, decomposition temperatures are normally significantly lower than with the heterogeneous catalysts mentioned above, and cyclopropane yields in general are higher. However, catalysts of type 2 must first be converted into the active form [presumably a copper(I) monochelate] by brief heating or by in situ reduction (see Table 10). Another soluble catalyst, copper(I) triflate, even decomposes diazoacetic esters and diazomalonic esters at temperatures below 0 °C and sterically more encumbered diazocarbonyl compounds (e.g. a-diazo-a-trialkylsilyl acetic esters " ) still at room temperature, and has shown its effectiveness in a number of cyclopropanation reactions. Since copper(I) triflate is... 

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... 

Thermal conversion of diazirines to linear diazo compounds was postulated occasionally and proved by indirect methods. The existence of a diazo compound isomeric to diazirine (197) was proved spectroscopically on short thermolysis in DMSO (76JA6416). An intermediate diazoalkane was trapped by reaction with acetic acid, yielding the ester (198) (77JCS(P2)1214). 

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). 

Although the present procedure illustrates the formation of the diazoacetic ester without isolation of the intermediate ester of glyoxylic acid />-toluenesulfonylhydrazone, the two geometric isomers of this hydrazone can be isolated if only one molar equivalent of triethylamine is used in the reaction of the acid chloride with the alcohol. The extremely mild conditions required for the further conversion of these hydrazones to the diazo esters should be noted. Other methods for decomposing arylsulfonyl-hydrazones to form diazocarbonyl compounds have included aqueous sodium hydroxide, sodium hydride in dimethoxyethane at 60°, and aluminum oxide in methylene chloride or ethyl acetate." Although the latter method competes in mildness and convenience with the procedure described here, it was found not to be applicable to the preparation of aliphatic diazoesters such as ethyl 2-diazopropionate. Hence the conditions used in the present procedure may offer a useful complement to the last-mentioned method when the appropriate arylsulfonylhydrazone is available. 

Carbene insertion into the O-H bond of alcohols is especially versatile for the formation of ethers. Diazomethane has been used, but other diazo compounds have also been used even those with fluorine in the carbene species. Rhodium acetate seems to be the catalyst of choice for the decomposition of a-diazo esters. Different alcohols 21 react with compound 22 to give fluorinated ethers 23 in good yield. ... 

Tricyclic compound 371 was produced from diazoacetic ester 372 by the rhodium(II) acetate-catalyzed insertion into the C—H bond at the tertiary C atom and located in the e-position with respect to the diazo group (84JA5295). [2-(Alkoxymethyl)phenyl] carbenes generated by the photolysis of diazo compounds 373 undergo intramolecular C—H insertion with the formation of benzodihydropyran derivatives 374 in 32-96% yield (89JA1465 94TL1699). 

Allyldiethylamine behaves similarly, but the yields are low since neither the starting amine nor the products are stable to the reaction conditions. For the efficiency of the cyclopropanation of the allylic systems under discussion, a comparison can be made between the triplet-sensitized photochemical reaction and the process carried out in the presence of copper or rhodium catalysts whereas with allyl halides and allyl ethers, the transition metal catalyzed reaction often produces higher yields (especially if tetraacetatodirhodium is used), the photochemical variant is the method of choice for allyl sulfides. The catalysts react with allyl sulfides (and with allyl selenides and allylamines, for that matter) exclusively via the ylide pathway (see Section 1.2.1.2.4.2.6.3.3. and Houben-Weyl, Vol. E19b, pll30). It should also be noted that the purely thermal decomposition of dimethyl diazomalonate in allyl sulfides produces no cyclopropane, but only the ylide-derived product in high yield.Very few cyclopropanes have been synthesized by photolysis of other diazocarbonyl compounds than a-diazo esters and a-diazo ketones, although this should not be impossible in several cases (e.g. a-diazo aldehydes, a-diazocarboxamides). Irradiation of a-diazo-a-(4-nitrophenyl)acetic acid in a mixture of 2-methylbut-2-ene and methanol gave mainly l-(4-nitrophenyl)-2,2,3-trimethylcyclo-propane-1-carboxylic acid (19, 71%) in addition to some O-H insertion product (10%). ... 

Diazo ester/rhodium(II) carboxylate combinations other than EDA/Rh2(OAc)4 have been tested It turned out that the solubility of the rhodium(II) carboxylate greatly influenced the efficiency of cyclopropanation. For the reaction of monoolefins with ethyl diazoacetate, markedly higher yields than with Rh(II) acetate were obtained with the better soluble rhodium(II) butanoate and rhodium(II) pivalate, the latter one being soluble even in pentane. However, only poor yields resulted from the use of rhodium(Il) trifluoroacetate, even though this compound is readily soluble, Rh CCFjCOO), in contrast to the other rhodium(II) carboxylates, is able to form 1 1 complexes with olefins particularly with electron-rich ones thus, competition of olefin and diazo compound for the only available coordination site at the metal atom could be responsible for the reduced catalytic action of Rh2(CF3COO)4 (as will be seen in Section 4.1, this complex is an excellent catalyst for cyclopropanation of aromatic substrates). The diazoester substituent also has some influence on the yields. Increasing yields were obtained in the series methyl ester, ethyl ester, n-butyl... 

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