Reactions of diazo esters

Removal of elemental nitrogen a. Reactions of diazo esters 

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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 oxonium ylide 390 is generated by the interaction of carbene with the unshared electron pair of the oxygen atom of ether 389, and subsequent sigmatropic rearrangement affords 391 [126]. The reaction was applied to the diastereoselective construction of 2,8-dioxabicyclo[3.2.1]octane, the core system 394 of zaragozic acid. The Rh-catalysed reaction of diazo ester 392 generates the bicyclic oxonium ylide 393 from the acetal, and its exocyclic 2,3-shift affords 394 [127]. 

An interesting application is the synthesis of bromofluoroacetate esters by the reaction of diazo esters with A -broraosuccinimide and hydrogen fluoride. ... 

This reaction was first reported by Buchner and Curtius in 1885 and subsequently by Schlotterbeck in 1907. It is the reaction for forming ketones from aldehydes and aliphatic diazo compounds and is thus known as the Buchner-Curtius-Schlotterbeck reaction. This reaction has been extended to synthesize jS-keto esters from the condensation between diazo esters and aldehydes." It should be pointed out that epoxides and aldehydes are also produced in this reaction, and the preparation of keto esters can also be performed in the presence of Lewis acids or via a two-step process involving an Aldol Reaction of diazo ester and aldehyde followed by the oxidative elimination of nitrogen. ... 

The catalytic production of olefins, diethyl maleate and fumarate, from ethyl diazoacetate has been reported with osmium [ 149] and ruthenium [ 128] porphyrins. Despite the periodic relationship of ruthenium to iron and osmium and the syntheses of different carbene complexes of ruthenium porphyrins, developed by Collman et al. [125-127], it is only very recently that cyclopropanation [135,171] and ethyl diazoacetate insertion into heteroatom bond reactions [172] were observed using ruthenium porphyrins as catalysts. The details of the catalytic reaction of diazo esters with simple olefins catalyzed with ruthenium porphyrins have been reported [173]. Product yields. 

Vinylketene 146 forms in 100% conversion from rhodium catalyzed reaction of diazo ester 145 as observed by NMR, and subsequent [2 + 2] cycloaddition with imine 147 gives the p-lactam 148 (Eqn (4.89)). ... 

What evidence is there for the individual reaction steps The add-base reaction (Eq, 2) has the characteristics of a Broensted equilibrium, as has been shown in the case of diazomethane-benzoic acid (in toluene). Further evidence for this is provided by the reactions of diazoacetic ester and diazo ketones. The occurrence of free, mobile diazonium cations is also supported by the fact that solutions of diazomethane in methanol show greater conductivity than solutions of pure solvent. ... 

Reaction of halo esters or diazo esters with boranes... 

A number of these alkylation reactions are illustrated in Scheme 9.2. Entries 1 and 2 are typical examples of a-halo ester reactions. Entry 3 is a modification in which the highly hindered base potassium 2,6-di-f-butylphenoxide is used. Similar reaction conditions can be used with a-halo ketones (Entries 4 and 5) and nitriles (Entry 6). Entries 7 to 9 illustrate the use of diazo esters and diazo ketones. Entry 10 shows an application of the reaction to the synthesis of an amide. 

The reaction of activated methylene groups with tosyl azide to yield the corresponding diazo derivatives proceeds in high yield [23]. The phase-transfer catalysed reaction is sensitive to the strength of base used the reaction of acetoacetic esters requires relatively mild conditions, otherwise diazoacetic esters are produced (Table 5.41). 

Carbonyl ylides possess versatile reactivities, among which the 1,3-dipolar cycloaddition is the most common and important reaction. The reaction sequence of ylide formation and then 1,3-dipolar cycloaddition can occur in either inter- or intramolecular manner. When the reaction occurs intermolecularly, the overall reaction is a one-pot three-eomponent process leading to oxygen-containing five-membered cyclic compounds, as demonstrated by the example shown in Scheme 8. A mixture of diazo ester 64, benzaldehyde, and dimethyl maleate, upon heating to reflux in CH2CI2 in the presence of 1 mol% rhodium(ii) perfluorobutyrate [Rh2(pfb)4], yields tetrahedrofuran derivative 65 in 49% yield as single diastereomer. " ... 

A recent example of this intramolecular tandem transformation is the Rh(ii)-catalyzed reaction of diazo keto ester 71. Depending on the structure of the diazo compound, a push-pull dipole intermediate derived from 71 can be trapped either by a tethered vinyl group (when n = 0) or by an indole 7r-bond (when n=l) (Equation (11)). This result clearly demonstrates a critical role of the conformation of the cycloaddition transition state. 

Dyes containing the pyridinium group linked to the diazo component via a carboxylic ester function (e.g., 40) [32017-47-3] are obtained by condensation of 4-nitrobenzoyl chloride with chloroethanol, reaction of the ester with pyridine, reduction of the nitro to an amino group, diazotization, and coupling with aromatic amines [124],... 

These two reactions of diazo compounds with carboxylic acids give gaseous nitrogen and esters as products. In both cases the rate of the reaction is proportional to [diazo compound]-[RCC H], Use the data for each reaction to suggest mechanisms and comment on the difference between them. 

The best results are obtained with trisyl azide, which again leads to high yields of the azide transfer product 2, especially if the enolate 1 is added to trisyl azide (see entries 1 and 2). Interestingly, the best chemoselectivity and, in addition, identical yields of azide (73%) result from the reaction of the lithium enolate with trisyl azide (entry 3). The reaction of the ester enolate 1 with trisyl azide is less sensitive to the nature of the enolate metal than is the corresponding imide enolate reaction (see Section 7.1.1.). Acetic acid quench, on the other hand, again proved to be useful. Unfortunately, bis-azidation to 3 and diazo transfer to 4 are also observed. 

These two reactions of diazo compounds with carboxylic acids give gaseous nitrogen and esters as products. In both cases r--... 

An interesting and potentially useful sequence is shown in equation (107). Cyclopropane esters (305) may be prepared by the addition of diazo esters (304) to double bonds under elimination of nitrogen. After saponification the acid is 0-protonated to open the cyclopropane ring, and the resulting carbenium ion (306) is trapped by lactonization. In effect a "y-lactone has been annulated to a double bond in a re-giodefined manner.Examples are given in Scheme 10. A related reaction involves the conversion of the cyclopropane ester (307) into the lactone (308 equation 108). ... 

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... 

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