Diazoesters

The photolysis or pyrolysis of diazoesters is the only source of carboalkoxy-carbenes and although numerous examples can be found in the literature concerning the reactivity of these carbenes, very little information is available on the kinetics of the decomposition. The photolysis of methyldiazoacetate yields carbo-methoxycarbene which adds stereospecifically to 2-butene. The quantum yield of the photolysis of ethyldiazoacetate has been determined in various solvents at different wavelengths (Table 12) . Thermal decomposition occurs above 150 °C although the presence of catalysts greatly accelerate the decomposition . Carboalkoxycarbenes are very selective with respect to insertion reactions, due to 

In alcoholic solution, in addition to the carbene-forming C-N cleavage reaction a concurrent heterolytic dissociation has recently been proposed which gives rise to a ketene-diazonium ion pair, viz. 

This is somewhat reminiscent of the mechanism postulated by Day and Whiting for the heterolytic dissociation of the intermediate vinyldiazoalkane in the photolysis of 3-(r-acyloxyalkyl)-5,5-dimethylpyrazolines. 

In alcoholic solution carboalkoxycarbenes also readily undergo a Wolff-type 

Thus the gas phase photolysis of ethyldiazoacetate yields equal amounts of Nj 

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Depending on the fluonnating agent, diazoalkanes, diazoketones, and diazoesters can undergo hydrofluorination, halofluonnation, and geminal difluonnation reactions... 

Chloroximes and enamines have provided aminoisoxazolines which could readily be converted to isoxazoles with acid (610-612). Pyrrazoles were usually obtained from addition of chlorohydrazones to enamines (610,613). The intermediate aminopyrazolines could only be isolated from the reaction of the cyclopentenyl enamine system. Pyrazoles were also obtained from the reactions of enamines with a-diazoketones and a-diazoesters (614). 

The transformation of diazoester 74c to benzenoic diester 189, catalyzed with Pd(C3H5)2Cl2, proceeded as a spontaneous selenium extrusion from unstable seleniepine 188 (90AG450). 

This area of research has only recently attracted the attention of synthetic organic chemists, but there has been a flurry of impressive activity in the area. Simple (i. e., unstabilized) carbenes suffer from many of the problems of nitrenes (vide infra) and most reported synthetically useful procedures use carbenoids the majority of recent reports have focussed upon reactions between a-diazoesters and imines in the presence of a range of catalysts. In one of the earliest reports of enantioselective carbene-imine reactions, for instance, Jacobsen and Finney reported that ethyl diazoacetate reacts with N-arylaldimines in the presence of cop-per(i) hexafluorophosphate with mediocre stereoselectivity to give N-arylaziridine carboxylates. Though the diastereoselectivities of the reaction were often acceptable (usually >10 1, in favor of the cis isomers) the observed enantioselectivity was low (no more than 44% ee Scheme 4.27) [33],... 

Williams and Johnston have reported the first use of proton catalysis in the aziridination of imines by diazoesters (Scheme 4.30) [38]. A range of aryl and ali-... 

Diazoester aziridinations may be carried out in ionic liquids [39]. Other carbene equivalents have been investigated in aziridination reactions, though not to the same extent as diazocarbonyl compounds. Dibromo(tert-butyldimethylsilyl)me-thyllithium, for example, aziridinates N-arylimines to give l-bromo-2-aryl-3-silyla-ziridines these compounds function as useful synthetic intermediates, reacting... 

Helquist s work on the use of diazomalonate in the synthesis of oxazoles has been extended to other diazocarbonyl compounds in our own laboratory.<92TL7769, 94T3761> Thus it was found that sulfonyl-, phosphonyl- and cyano-substituted diazoesters gave the corresponding 4-functionalised oxazoles 30 in acceptable yield (Scheme 20). In many cases the yield of oxazole was significantly improved by the use of rhodium(II) trifluoroacetamide as catalyst. The 4-cyano-oxazole 30 (R = Me, Z = CN) proved interesting in that it allowed the formation of a bis-oxazole 31 by a second rhodium catalysed reaction (Scheme 20). 

Dirhodhun (II) carboxylate catalyzed cyclization of a series of y-alkoxy-a-diazoesters has been shown to proceed with substantial diastereoselectrvity, producing the 2,3,5-trisubstituted tetrahydrofiirans. Hie diastereo selectivity of the cyclization improved as the electron-withdrawing ability of the substituent R increased (Scheme 22, <96JOC6706>). 

Transition metal catalyzed decomposition of diazoester 64b, which is available from 64a with TsNj/base, results in the formation of furo[3,4-b]indole 65. This intermediate is trapped intramolecularly in situ to give 66. Furo[3,4-b]indoles of type 67 can be prepared similarly... 

The most significant and widely studied reactivity of the ruthenium and osmium porphyrin carbene complexes is their role in catalyzing both the decomposition of diazoesters to produce alkenes and the cyclopropanation of alkenes by diazoesters. Ethyl diazoacetate is used to prepare the carbene complex 0s(TTP)(=CHC02Et)... 

Iron porphyrins display pronounced substrate preferences for alkene cyclopro-panation with EDA. In general, electron-rich terminal alkenes in conjunction with aromatic moiety or heteroatoms can efficiently undergo cyclopropanation with high catalyst turnover and selectivity. In contrast, 1,2-disubstituted alkenes cannot undergo cyclopropanation with diazoesters. Alkyl alkenes are poor substrates, giving cyclopropanated products in low yields. In both cases, the dimerization product diethyl maleate was obtained in high yield [53]. 

In 2004, ruthenium-catalysed asymmetric cyclopropanations of styrene derivatives with diazoesters were also performed by Masson et al., using chiral 2,6-bis(thiazolines)pyridines. These ligands were prepared from dithioesters and commercially available enantiopure 2-aminoalcohols. When the cyclopropanation of styrene with diazoethylacetate was performed with these ligands in the presence of ruthenium, enantioselectivities of up to 85% ee were obtained (Scheme 6.6). The scope of this methodology was extended to various styrene derivatives and to isopropyl diazomethylphosphonate with good yields and enantioselectivities. The comparative evaluation of enantiocontrol for cyclopropanation of styrene with chiral ruthenium-bis(oxazolines), Ru-Pybox, and chiral ruthenium-bis(thiazolines), Ru-thia-Pybox, have shown many similarities with, in some cases, good enantiomeric excesses. The modification... 

Another Rhn-catalyzed decomposition of a a-diazoester as described by Sabe and coworkers [198] was used for the synthesis of indolizidine alkaloids (Scheme 6/2.8). It can be assumed that, first, an ammonium ylide is formed which then undergoes a 1,2-shift with ring-expansion. Thus, reaction of 6/2-40 with Rh2(OAc)4 led to a 72 28 mixture of 6/2-41 and 6/2-42 in 85 % yield. Cu(acac)2 can also be used with even better yields, but lower selectivity (65 35). 

Scheme 6/2.7. Three-component reaction of a a-diazoester, an imine and an alkene.

A variety of silicon-functionalized diazoacetic esters are available by reacting (trifloxysilyl)- or (chlorosilyl)diazoacetic esters with appropriate nucleophiles [1]. Thermally, photochemically, or transition metal induced intramolecular carbene reactions of these novel diazoesters lead to four-, five-, and six-membered silaheterocycles. 

Reaction of ot-diazoester 413 with several copper carboxylate catalysts afforded azocyclooctene 414 along with perhydropyrido[2,l-r ][l,4]oxazin-l-one 415 (Equation 77) <1996TL2165>. 

Diazoesters 422 were subjected to the action of Rh2(OAc)4 to give optically active methyl (4.Y,11 a.S )-1 -oxo-l,3,4,6,ll,lla-hexahydro[l,4]oxazino[4,3-A isoquinoline-4-carboxylates 423 (Equation 79) <1995SL237>. 

Pd(OAc)2 works well with strained double bonds as well as with styrene and its ring-substituted derivatives. Basic substituents cannot be tolerated, however, as the failures with 4-(dimethylamino)styrene, 4-vinylpyridine and 1 -vinylimidazole show. In contrast to Rh2(OAc)4, Pd(OAe)2 causes preferential cyclopropanation of the terminal or less hindered double bond in intermolecular competition experiments. These facts are in agreement with a mechanism in which olefin coordination to the metal is a determining factor but the reluctance or complete failure of Pd(II)-diene complexes to react with diazoesters sheds some doubt on the hypothesis of Pd-olefin-carbene complexes (see Sect. 11). 

Cu(OTf)2 generally gives yields intermediate between those of the other two catalysts, but with a closer resemblance to rhodium. In competition experiments, the better coordinating norbomene is preferred over styrene, just as in the case with Pd(OAc)2. Cu(acac)2, however, parallels Rh2(OAc)4 in its preference for styrene. These findings illustrate the variability of copper-promoted cyclopropanations, and it was suggested that in the Cu(OTf)2-catalyzed reactions of diazoesters, basic by-products, which are formed as the reaction proceeds, may gradually suppress... 

Whereas control of the rate of addition of the diazoester generally meets with increased yields when Rh OAc), Rh6(CO)16 and CuCl P(OR)3 are used, it has no effect on cyclopropane yields in the case of PdCl2 2 PhCN 59). 

With the rhodium and copper catalysts, even the combination of equimolar amounts of olefin and diazoester will allow high yields of cyclopropanes if the addition rate is controlled meticulously (see Table 6 for examples). This circumstance is particularly useful for cyclopropanation of olefins which are in short supply. In combination with Rhg(CO)16, the easy recovery of the unchanged catalyst (by diluting the mixture with hexane and separating the precipitated catalyst from the liquid65 may render such a procedure particularly attractive from an economical point of view. 

Cyclopropanation of C=C bonds by carbenoids derived from diazoesters usually occurs stereospeciflcally with respect to the configuration of the olefin. This has been confirmed for cyclopropanation with copper 2S,S7,60 85), palladium 86), and rhodium catalysts S9,87>. However, cyclopropanation of c -D2-styrene with ethyl diazoacetate in the presence of a (l,2-dioximato)cobalt(II) complex occurs with considerable geometrical isomerization88). Furthermore, CuCl-catalyzed cyclopropanation of cis-2-butene with co-diazoacetophenone gives a mixture of the cis- and trans-1,2-dimethylcyclopropanes 89). 

As it is known from experience that the metal carbenes operating in most catalyzed reactions of diazo compounds are electrophilic species, it comes as no surprise that only a few examples of efficient catalyzed cyclopropanation of electron-poor alkeiies exist. One of those examples is the copper-catalyzed cyclopropanation of methyl vinyl ketone with ethyl diazoacetate 140), contrasting with the 2-pyrazoline formation in the purely thermal reaction (for failures to obtain cyclopropanes by copper-catalyzed decomposition of diazoesters, see Table VIII in Ref. 6). 

Palladium(II) acetate was found to be a good catalyst for such cyclopropanations with ethyl diazoacetate (Scheme 19) by analogy with the same transformation using diazomethane (see Sect. 2.1). The best yields were obtained with monosubstituted alkenes such as acrylic esters and methyl vinyl ketone (64-85 %), whereas they dropped to 10-30% for a,p-unsaturated carbonyl compounds bearing alkyl groups in a- or p-position such as ethyl crotonate, isophorone and methyl methacrylate 141). In none of these reactions was formation of carbene dimers observed. 7>ms-benzalaceto-phenone was cyclopropanated stereospecifically in about 50% yield PdCl2 and palladium(II) acetylacetonate were less efficient catalysts 34 >. Diazoketones may be used instead of diazoesters, as the cyclopropanation of acrylonitrile by diazoacenaph-thenone/Pd(OAc)2 (75 % yield) shows142). 

EvenPd(OAc)2 is not effective in catalyzing the cyclopropanation of a,P-unsaturated nitriles by ethyl diazoacetate. Instead, vinyloxazoles 92 are formed from acrylonitrile or methacrylonitrile by carbenoid addition to the CsN bond 143 Diethyl maleate and diethyl fumarate as well as polyketocarbenes are by-products in these reactions the 2-pyrazoline which would result from initial [3 + 2] cycloaddition at the C=C bond and which is the sole product of the uncatalyzed reaction at room temperature, can be avoided completely by very slow addition of the diazoester... 

As has already been mentioned for cyclopropanation of olefins, the diazoester should be added slowly to the mixture of alkyne and Rh2(OAc)4, in order to minimize formation of carbene dimers. The reaction works well with mono- and... 

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