Decomposition of a-diazo esters

The decomposition of a-diazo esters by a ruthenium porphyrin catalyst has been used by Che and co-workers in a multicomponent strategy directed toward functionalized pyrrolidines 172. The first step involves the formation of a ruthenium... 

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. ... 

Photolytic and catalytic decomposition of a-diazo esters produces )8-lactones, which are formed via intramolecular C—H insertion of a carbene or carbenoids. Tertiary alkyl esters of diazomalonic acid are decomposed by rhodium acetate with exclusive formation of the four-membered ring 211. This suggests a smooth insertion into the C—H bond activated by the adjacent oxygen atom (90TL1023). jS-Lactone 212 was obtained by photolysis of diazo malonic ester 213 (71CC577). 

A Hammett Analysis In a Multlstep Reaction Rhodium(ll)-Catalyzed Decomposition of a-Diazo Esters... 

A good example for a detailed Hammett correlation study is the rhodium(II)-catalyzed decomposition of a-diazo esters. The most likely mechanism for the a-diazo ester decomposition process involves the initial complexation of the nega-... 

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... 

The combined ether solutions are then subjected to distillation at 20° or below under the vacuum obtainable from a water pump until all the ether is removed. Prolonged distillation results in decomposition of the diazo ester and in a decreased yield. The yellow residual oil is practically pure ethyl diazoacetate and is satisfactory for most synthetic purposes (Note 3). The yield is about 98 g. (85%) (Notes 4 and 5). 

Decomposition of the diazo ester 395 in presence of dirhodium tetraacetate gives the zwitterionic intermediate 396, which undergoes a 1,3-dipolar cycloaddition with the double bond of the adjacent vinylindole. The bridged compound is isolated in good yield when the reaction is carried out at room temperature however, at 50 °C or above, compound 397 is the only compound isolated, again in good yield (Scheme 93) <2005JOC2206>. 

In 1966, Nozaki et al. reported that the decomposition of o-diazo-esters by a copper chiral Schiff base complex in the presence of olefins gave optically active cyclopropanes (Scheme 58).220 221 Following this seminal discovery, Aratani et al. commenced an extensive study of the chiral salicylaldimine ligand and developed highly enantioselective and industrially useful cyclopropanation.222-224 Since then, various complexes have been prepared and applied to asymmetric cyclo-propanation. In this section, however, only selected examples of cyclopropanations using diazo compounds are discussed. For a more detailed discussion of asymmetric cyclopropanation and related reactions, see reviews and books.17-21,225... 

A new synthesis of cr-substituted and a,a-disubstituted a-amino acid derivatives based on the ammonium ylide formation/[2,3]-sigmatropic rearrangement has been recently reported by Clark s group.Decomposition of a-diazo -keto ester 153 was studied in detail with Rh2(OAc)4, Cu(acac)2, and Cu(hfacac)2 as the catalyst. Cu(acac)2 and Cu(hfacac)2 gave similar results, but Rh2(OAc)4 turned out less effective (Equation (23)). 

In addition to copper and rhodium catalysts commonly used in the generation of metal carbene complexes, other transition metals have also been explored in the diazo decomposition and subsequent ylide generation.Che and co-workers have recently studied ruthenium porphyrin-catalyzed diazo decomposition and demonstrated a three-component coupling reaction of a-diazo ester with a series of iV-benzylidene imines and alkenes to form functionalized pyrrolidines in excellent diastereoselectivities (Scheme 20). ... 

Cyclizations can occur with heteroatoms present in the tether as long as the groups are not strongly nucleophilic. Decomposition of a-diazo- 3-arylmethanesulfonyl esters (173) resulted in the formation of 1,3-dihydrobenzo[c]thiophene 2,2-dioxides (174 equation 38),143 which are valuable precursors to o-quinodimethanes. Reaction with /V-aryldiazoamides (175) has been shown to be a useful method for preparing 2(3//)-indolinones (176 equation 39),22a while reaction of a-diazo-(3-keto esters (177) has been developed as a process to synthesize 3-acetylbenzofiiran-2(3//)-ones (178 equation 40).144... 

Summary. Intra- and intermolecular carbene or carbenoid reactions resulting from the photochemical and Cu(I)-, Rh(II)-, or Ru(I)-catalyzed decomposition of a-diazo-a-silylacetic esters are described. Among the products reported are (alkoxysilyl)ketenes, silaheterocycles, 1-trialkylsilylcyclopropane-l-carboxylates, and products derived from transient carbonyl ylides. 

Decomposition of a-diazo ketoamides 208 in the presence of substituted propiolic esters gives spirocyclic oxiranes 209. The reaction involves intramolecular addition of a rhodium carbenoid onto the oxygen atom of the amide group to yield the carbonyl ylide, which, after 1,4-H-migration, produces a cyclic ketene N,0-acetal 210. The latter further reacts with the activated triple bond of the dipolarophile to form a zwitterionic intermediate and, finally, a spirocycloadduct (Scheme 26) (90JA2037). 

Ottmann with the following results. They found that a trace of heavy metal catalyzes decomposition of the diazo ester and so heated a mixture of the ester with 20 parts of benzene in a glass insert of an autoclave at 136-140° and so obtained 7-carbo-ethoxynorcaradiene (1) in much improved yield. The ester (I) is converted into the amide (2), which on alkaline hydrolysis undergoes rearrangement to a mixture of four cycloheptatrienecarboxylic acids. Characterization of these acids led to assignment of the structures formulated. 

The subsequent fast decomposition of the diazo esters is of special interest in that it relates to the step in which nitrogen is lost in the nitrous acid deamination of aliphatic amines. The gross mode of decomposition of the diazo ester (34) is a function of the nature of the alkyl group R, and in general terms, substitution, /3-elimination or a-elimination occurs (equation 115). 

Aldehydes react with the lithio-derivatives of a-diazo-esters to give /3-hydr-oxy>a-diazo-esters, which in turn undergo rhodium(ii)-catalysed decomposition to give /3-keto-esters./3-Keto-amides are obtained in moderate to high yield from the acylation of amide enolates with mixed anhydrides. In a general reaction, orthoformates react with acidic methines to give /3-keto-aldehydes, isolated as their dialkyl acetals [equation (16)]. ... 

Ethyl 2-fluoroethoxyacetate, F [CH2]2 0 CH2 C02Et, could not be prepared by the action of ethyl diazoacetate on pure redistilled 2-fluoroethyl alcohol, and the addition of a small quantity of concentrated hydrochloric acid had no effect, which is rather surprising in view of the known catalytic action of acids on the decomposition of the diazoacetic ester. However, fluoroethyl alcohol which had not been specially dried reacted immediately with ethyl diazoacetate with a vigorous evolution of nitrogen and the simultaneous disappearance of the yellow colour of the diazo ester. 

A study of Rh2Ln4-catalyzed decomposition of 2-diazo-A-phenylmalo-namic acid ethyl ester 128 (R = C02Et) showed, that with perfluorocarbox-amides as catalyst ligands, the aromatic C—H insertion giving rise to oxindoles 129 occurs in preference to aliphatic C—H insertion, addition to C=C and C=C bonds, O—H insertion, and ylide formation, all of which are observed simply by switching to a carboxylate-based rhodium catalyst (94JOC2447). 

When a carbene center and a nitrogen are linked by a four-carbon chain, insertion into the N — H bond gives rise to piperidine derivatives. The rhodium(II) acetate-catalyzed decomposition of either diazo ketones 158 (92TL6651) or diazo ester 159 (85JOC5223) leads to insertion into the amide N — H bond to give products in moderate yields. Various solvents, temperatures, and catalyst concentrations were found to be important in determining the yield and the product distribution in the cyclization of 159. 

Intramolecular cyclopropanation of olefinic a-diazo ketones and a-diazo esters has been widely used in organic synthesis. When a carbenoid center and the double bond are separated by a chain of three atoms, one of which is oxygen, a five-membered O-containing heterocycle is formed. Intermolecular cyclopropanations of olefins are known to allow stereospecific formation of desired products. Thus, decomposition of substituted allyl diazomalonates 265 in the presence of copper salts gives rise to bicyclic... 

The first step in the decomposition of nitrosoamides 123) is formation of the diazo ester 125) which fragments to a diazonium ion pair (128)129 The ion pairs thus produced differ from those obtained in the reaction of diazoalkanes with acids. The ratio of ester to ether formed in the decomposition of rV-nitroso-fV-benzhydrylbenz-amides in alcohol is lower than that found in the reaction of diphenyldiazomethane 132) with acids, and in the solvolysis of benzhydryl benzoate (I35)135,136 This effect has been attributed to the intervention of trans-diazo ester in the decomposition of 125) which leads to a greater distance between carbocation and carbox-ylate anion. In the diazoalkane reaction attack of the acid occurs at the electron-rich carbon atom to generate the carboxylate in the immediate vicinity of the incipient carbocation. 

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%). ... 

Transition metal catalyzed decomposition of unsaturated a-diazo ketones or a-diazo esters is a powerful method for the synthesis of certain 2-oxobicyclo[n.l.0]alkanes. In contrast to the thermal (see Section 1.2.1.2.4.2.6.1.) and photochemical (see Section I.2.I.2.4.2.6.2.) methods, which have only been applied successfully in a few cases, the carbenoid version has been extensively utilized for the construction of simple or highly substituted bicyclic, tricyclic or higher systems of predictable stereochemistry (for reviews, see refs 2, 82, 320). Several of the cyclopropanes so obtained have been transformed further into natural products with diverse molecular skeletons. As examples and procedures have already been presented in Houben-Weyl, Vol. E19b, ppl088ffand 1271 ff, only some important aspects concerning the scope and limitation of the method as well as recent developments concerning its stereochemistry will be discussed here. 

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