Catalyzed decomposition of diazo ester

Functionalized cyclopropenes are viable synthetic intermediates whose applications [99.100] extend to a wide variety of carbocyclic and heterocyclic systems. However, advances in the synthesis of cyclopropenes, particularly through Rh(II) carboxylate—catalyzed decomposition of diazo esters in the presence of alkynes [100-102], has made available an array of stable 3-cyclopropenecarboxylate esters. Previously, copper catalysts provided low to moderate yields of cyclopropenes in reactions of diazo esters with disubstituted acetylenes [103], but the higher temperatures required for these carbenoid reactions often led to thermal or catalytic ring opening and products derived from vinylcarbene intermediates (104-107). 

The intramolecular insertion into the N—H bond of j8-lactams was used successfully in the synthesis of bicyclic ring systems. Photochemical, in contrast to Rh(II)-catalyzed, decomposition of diazo ester 62 was found to occur far less selectively. In the photolytic reaction, the imide 63 is the major product. It presumably arises by a photolytic Wolff rearrangement to a ketene intermediate, which is trapped intramolecularly. With Rh2(AcO)4 catalyst the Wolff rearrangement is suppressed and 62 undergoes ring closure to 64 nearly quantitatively (80TL31). 

Rhodium(II) octanoate-catalyzed decomposition of diazo esters 52, involving in the first stage a reaction of a carbenoid with the pyrrole double bond, furnishes polycyclic lactones 53 (34-79% R = H, Me R = H, Ph) (94TL5209) as shown in Scheme 18. 

The reaction of dichlorocarbene with ketones and diamines results in near quantitative formation of a mixture piperazinones 584 and 585 (80JOC754). As shown in Section III,C,2, piperazine 78 [R = H, R + R = (CH2)s], the minor product of the Rh2(OAc)4-catalyzed decomposition of diazo ester 73, is the result of the dimerization of the intermediate ylide 76 (84JOC113). Tetrahydropyrazines were synthesized through ring expansion of imidazolidines. Thermolysis or photolysis of diazo compounds... 

Rhodium(II) acetate-catalyzed decomposition of diazo ester 677 gives oxacepham 678 via the formation of oxonium ylide 679 and its subsequent fragmentation (91CC1235). 

Various cyclopropanated molecules such as chrysanthemic acid, and pyrethrins are well known as nonpolluting insecticides, and one of the synthetic routes to these biologically active compounds appeals to the copper or rhodium catalyzed decomposition of diazo esters to promote the generation of the reactive carbenoid species [103]. 

The Hammett correlation study on the Rh(II)-catalyzed decomposition of diazo esters 1 indicates that the reaction is accelerated by the presence of electron-donating groups in flie aromatic ring. The excellent correlation with ct suggest that the second step of flie reaction (formation of the Rh(II) carbene intermediate 4) is more sensitive to electronic effects than the initial pre-equilibrium. 

In this review an attempt is made to discuss all the important interactions of highly reactive divalent carbon derivatives (carbenes, methylenes) and heterocyclic compounds and the accompanying molecular rearrangements. The most widely studied reactions have been those of dihalocarbenes, particularly dichlorocarbene, and the a-ketocarbenes obtained by photolytic or copper-catalyzed decomposition of diazo compounds such as diazoacetic ester or diazoacetone. The reactions of diazomethane with heterocyclic compounds have already been reviewed in this series. ... 

The strained bicyclic carbapenem framework of thienamycin is the host of three contiguous stereocenters and several heteroatoms (Scheme 1). Removal of the cysteamine side chain affixed to C-2 furnishes /J-keto ester 2 as a possible precursor. The intermolecular attack upon the keto function in 2 by a suitable thiol nucleophile could result in the formation of the natural product after dehydration of the initial tetrahedral adduct. In a most interesting and productive retrosynthetic maneuver, intermediate 2 could be traced in one step to a-diazo keto ester 4. It is important to recognize that diazo compounds, such as 4, are viable precursors to electron-deficient carbenes. In the synthetic direction, transition metal catalyzed decomposition of diazo keto ester 4 could conceivably furnish electron-deficient carbene 3 the intermediacy of 3 is expected to be brief, for it should readily insert into the proximal N-H bond to... 

Cyclopropyl lactones. Copper-catalyzed decomposition of unsaturated esters of dia-zoacetic acid can provide eyclopropyl lactones >2, 83). The soluble copper chelate 1 is superior for this purpose to copper powder or copper oxide. In a typical example, the lactone 3 is obtained from the diazo ester 2 in 92% yield. 

The copper-catalyzed pyrolysis of diazo ketone 139 (R = O, R = H) gives pyrrolizine 140 in quantitative yield (83HCA2666). However, the decomposition of diazo ester 139 (R = H2, R = C02Et) is not preparatively useful, since a mixture of 141 and ester 142 was obtained in a yield of 35%, at best (83CJC454). 

The existing alternative preparative methods for the a diazo esters, such as diazotization of glycine esters, p3TolysIs of TYacylYVnltrosoglydne esters, hase-catalyzed cleavage of 0 dlazo ketoacetates, reactions of alkoxycarhonylmethylene phosphoranes with arenesulfonyl azides, or add catalyzed decomposition of acetic esters with aryltriazene substituents, all... 

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... 

Intermediate 37 can be transformed into ( )-thienamycin [( )-1)] through a sequence of reactions nearly identical to that presented in Scheme 3 (see 22— 1). Thus, exposure of /(-keto ester 37 to tosyl azide and triethylamine results in the facile formation of pure, crystalline diazo keto ester 4 in 65 % yield from 36 (see Scheme 5). Rhodium(n) acetate catalyzed decomposition of 4, followed by intramolecular insertion of the resultant carbene 3 into the proximal N-H bond, affords [3.2.0] bicyclic keto ester 2. Without purification, 2 is converted into enol phosphate 42 and thence into vinyl sulfide 23 (76% yield from 4).18 Finally, catalytic hydrogenation of 23 proceeds smoothly (90%) to afford ( )-thienamycin... 

Ring enlargement via an insertion of a carbene generated in the a-position to the ring is an established method and has also been applied to the synthesis of oxepins. The ()3-allylpalladium chloride catalyzed decomposition of substituted ethyl diazo(4/7-pyran-4-yl)acetates in benzene at room temperature gives ethyl oxepin-4-carboxylates 1 in excellent yield.190 The ester function can be replaced by the phosphonate group and other P = 0-functions (see Houben-Weyl,... 

Wolff rearrangement of a-diazoketones to give ketenes or subsequent products is an often used synthetic procedure the scope and limitations of which are well established 13 390), so that only a few new features of this reaction need to be considered here. Concerning its catalytic version, one knows that copper, rhodium and palladium catalysts tend to suppress the rearrangement390). A recent case to the contrary is provided by the Rh2(OAc)4-catalyzed decomposition of ethyl -2-diazo-3-oxopent-4-enoates 404 from which the p,y-unsaturated esters 405 are ultimately obtained via a Wolff rearrangement 236). The Z-5-aryl-2-diazo-3-oxopent-4-enoates undergo intramolecular insertion into an aromatic C—H bond instead (see Sect. 4.1). 

Silanes can react with acceptor-substituted carbene complexes to yield products resulting from Si-H bond insertion [695,1168-1171]. This reaction has not, however, been extensively used in organic synthesis. Transition metal-catalyzed decomposition of the 2-diazo-2-phenylacetic ester of pantolactone (3-hydroxy-4,4-dimethyltetrahydro-2-furanone) in the presence of dimethyl(phenyl)silane leads to the a-silylester with 80% de (67% yield [991]). Similarly, vinyldiazoacetic esters of pantolactone react with silanes in the presence of rhodium(II) acetate to yield a-silylesters with up to 70% de [956]. 

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. 

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. 

The intramolecular carbenoid O — H insertion accompanying decomposition of diazo keto ester 592 leads, however, to the formation of the corresponding 1,4-oxazine derivative in 90% yield (94JOC2447). Similarly, the tetrahydroindeno[l,2-h]-l,4-oxazin-3(2//)-one system was stereoselectively synthesized via BF3-Et20- or Rh2(OAc)4-catalyzed ring closure of j8-hydro-xydiazoacetamides 593 (83JOC2675). 

Eight-membered N,0,S-containing ring systems 680 have become accessible via Rh2(OAc)4-catalyzed decomposition of diazomalonic or diazo-acetoacetic esters in the presence of penicillin derivatives 681. The reaction is mediated by sulfonium ylide 682 and proceeds stereoselectively but in moderate yields. The stereochemical migration control in the ylide occurs... 

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. 

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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