Ethyl diazopyruvate

Many of the early workers who studied the thermal decomposition reactions of diazocarbonyl compounds found that the addition of copper metal or copper salts allowed the reaction to be achieved at a lower temperature,<63AG(E)565, 64CB2628, 73JOU431> although no detailed study of this catalytic effect was undertaken. Alonso and Jano studied the copper-salt reaction of ethyl diazopyruvate 26 with acetonitrile and benzonitrile. The... 

Section B gives some examples of metal-catalyzed cyclopropanations. In Entries 7 and 8, Cu(I) salts are used as catalysts for intermolecular cyclopropanation by ethyl diazoacetate. The exo approach to norbornene is anticipated on steric grounds. In both cases, the Cu(I) salts were used at a rather high ratio to the reactants. Entry 9 illustrates use of Rh2(02CCH3)4 as the catalyst at a much lower ratio. Entry 10 involves ethyl diazopyruvate, with copper acetylacetonate as the catalyst. The stereoselectivity of this reaction was not determined. Entry 11 shows that Pd(02CCH3) is also an active catalyst for cyclopropanation by diazomethane. 

The comparison between the cycloaddition behavior of simple diazoketones and of ethyl diazopyruvate 56 towards the same olefin underlines the crucial influence of the ethoxycarbonyl group attached to the carbonyl function. This becomes once again evident when COOEt is replaced by an acetal function, such as in l-diazo-3,3-di-methoxy-2-butanone 86 with enol ethers and acetates, cyclopropanes rather than dihydrofurans are now obtained 113). ... 

For example, reaction of ethyl diazopyruvate with cyclohexene in the presence of rhodium 126) or copper113 126 catalysts furnishes, besides the 7-exo-substituted norcarane 108, a small amount of 110, which may arise either from allylic insertion or from the 7-mfo-substituted norcarane 109 by a thermal 1,5-homo-hydrogen shift. 

Ethyl diazopyruvate, under copper catalysis, reacts with alkynes to give furane-2-carboxylates rather than cyclopropenes u3) (Scheme 30). What looks like a [3 + 2] cycloaddition product of a ketocarbenoid, may actually have arisen from a primarily formed cyclopropene by subsequent copper-catalyzed ring enlargement. Such a sequence has been established for the reaction of diazoacetic esters with acetylenes in the presence of certain copper catalysts, but metallic copper, in these cases, was not able to bring about the ring enlargement14). Conversely, no cyclopropene derivative was detected in the diazopyruvate reaction. 

The reaction, formally speaking a [3 + 2] cycloaddition between the aldehyde and a ketocarbene, resembles the dihydrofuran formation from 57 a or similar a-diazoketones and alkenes (see Sect. 2.3.1). For that reaction type, 2-diazo-l,3-dicarbonyl compounds and ethyl diazopyruvate 56 were found to be suited equally well. This similarity pertains also to the reactivity towards carbonyl functions 1,3-dioxole-4-carboxylates are also obtained by copper chelate catalyzed decomposition of 56 in the presence of aliphatic and aromatic aldehydes as well as enolizable ketones 276). No such products were reported for the catalyzed decomposition of ethyl diazoacetate in the presence of the same ketones 271,272). The reasons for the different reactivity of ethoxycarbonylcarbene and a-ketocarbenes (or the respective metal carbenes) have only been speculated upon so far 276). 

Examples are known where intermolecular carbenoid transformations between diazomalonates or certain diazoketones and appropriate olefins result in competition between formation of cyclopropane and products derived from allylic C—H insertion2-4. For example, catalytic decomposition of ethyl diazopyruvate in the presence of cyclohexene gave the 7-ejco-substituted norcarane 93 together with a small amount of the allylic C—H insertion product 94 (equation 95)142 143. In some cases, e.g. rhodium(II) decomposition of a-diazo-j8-ketoester 95, the major pathway afforded C—H insertion products 96 and 97 with only a small amount of the cyclopropane derivative 98. In contrast, however, when a copper catalyst was employed for this carbenoid transformation, cyclopropane 98 was the dominant product (equation 96)144. The choice of the rhodium(II) catalyst s ligand can also markedly influence the chemoselectivity between cyclopropanation and C—H... 

The Cope rearrangement of c/j-di vinylcyclopropanes is thermally allowed and offers an attractive stereoselective approach to cycloheptadienes. Cyclopropanation reactions can be used to prepare divi-nylcyclopropanes, as shown in Scheme 23.120 Reaction of ethyl diazopyruvate with butadiene generated... 

Under similar conditions diazo acetoacetate does not afford cyclopropanes but dihydrofurans as 62 which can be aromatized (e.g. to 63)20). A different furan derivative 64 is obtained from ethyl diazopyruvate as outlined in Eq. 19 38). Possibly cyclopropanes are intermediates in these reactions, which rearrange to the five-membered heterocycles under the conditions employed. 

An example of enantioselective 1,3-dipolar cycloaddition of ethyl diazopyruvate to 2,3-dihydrofuran, catalyzed by a chiral ruthenium-PyBox complex, to provide a tetrahydrofurofuran was reported (Equation 125). However, the adduct 240 was only obtained in 74% ee, and its absolute configuration not determined <2004SL2573, 2005HCA1010>. As shown in Equation (126), 2,3-dihydrofuran also participated in 1,3-dipolar cycloaddition with dipoles derived from aziridines under Sc(OTf)3-catalyzed conditions, forming rfr-fused furopyrrolidines <2001TL9089>. 

Furane synthesis. Copper-catalyzed deco iposition of ethyl diazopyruvate (1) in the presence of cnol ethers or of alkynes provide a useful route to ethyl a-furoates. 

Use of ethyl diazopyruvate or l-diazo-3,3-dimethoxy-2-butanone for cyclopropanation introduces additional functionality into the ring-opened products . j -Methylene y-butyrolactones result from bisalkoxycarbonyl-substituted cyclopropanes in three steps (equation 85) . ... 

Thermolysis of ethyl diazopyruvate (136) in the presence of enol ethers and bis(acetylacetonato) copper(II) catalyst did not lead to cyclopropane formation but instead a dihydrofuran (140) was generated (equation 33) . 

Dihydrofuran derivatives 319 are formed as major products in Rh2(OAc)4-catalyzed reactions of a-diazoacetophenone with 2-methoxy-propene or a-methoxystyrene (84MI1). Copper chelate or rhodium(II) acetate-catalyzed 1,3-dipolar cycloaddition of metal carbenoids, generated from ethyl formyldiazoacetate (90JOC4975), ethyl diazopyruvate... 

Oxepin 404 was prepared by the reaction of ethyl diazopyruvate with 1,3-butadiene in 26% yield. The reaction involves a carbene addition to the double bond with formation of a mixture of cis- and trans-2-oxo-2-(2-... 

Within the framework of the above methodology, 2-methylenedioxole 554 is accessible by trapping a carbene with ketene 555 (77JOM155). Ethyl diazoacetate reacts with substituted cyclohexanones in the presence of Cu(acac)2 in a similar manner to produce spirodioxoles 556 (80JHC721), while the reaction of ethyl diazopyruvate with ketone 557 furnishes the 1 2 adduct 558 [88CI(L)631],... 

Dictyopterene C (15, R = H R = Bu) and dictyopterene D [15, R = H R = (Z)-CH = CHEt], the natural pheromones of brown algae, have been synthesized from both ci.i-16 and /ran.s-divinylcyclopropanes 14 via thermal rearrangements. Extensive racemiz-ation was observed when optically pure divinylcyclopropanes were used. Cycloheptadienes 15 (R = COjEt R = H, Ph) are also available heterocyclic analogs can be prepared via cyclopropanations of dienes with ethyl diazopyruvate (see Section 2.4.5.2.). ... 

Ethyl diazopyruvate (6) cyclopropanation of butadiene yields 7, dihydrooxepin 8, which can be prepared in excellent yield by the photolysis of oxovinylcyclopropane 7, and a small amount of dihydrofuran 9. ... 

A solution of ethyl diazopyruvate (6 5.00 g, 35.0 mmol) in dry CHjCl (400 mL) was added dropwise, within 8 h, into stirred suspension of rhodium(II) acetate dimer (20 mg, 0.04 mmol) in dry CHjCl (100 mL), in which an excess of liquid buta-1,3-diene (i.e. gaseous butadiene liquefied in a dry ice/acetone condenser) had been dissolved. More butadiene was added periodically and the reaction (at rt) was monitored by TLC (silica gel, hexane/EtOAc 4 1) for the disappearance of the diazo ester. The mixture was concentrated to a 10-mL volume and column chromatographed (silica gel, hexane/EtOAc 12 1) to give colorless liquid 7 yield 2.06 g (35%). 

For example, reaction of ethyl diazopyruvate with cyclohexene in the presence of rhodium or copper catalysts furnishes, besides the 7-exo-substituted... 

Aryl- and alkylthioamides react with ethyl diazopyruvate in the presence of boron trifluoride etherate to give 2-substituted-4-carbetoxythiazoles <95JHC937>. 

Reaction of 2,3-dihydro-1,4-dioxin with ethyl diazopyruvate over (trimethylphosphino)copper(I) chloride produces dihydrofuroic ester (114) and a similar reaction with dimethyl diazomalonate, followed by acid hydrolysis, afforded the lactone ester (115) <85JOC4681>. 

Chain-extension of aldoses or dialdoses with ethyl diazopyruvate furnished sugar 2,4-diketoesters, such as compounds (29) and (30), respectively, suitable for transformation into complex carbohydrates containing heterocyclic moieties, and Pd-catalysed trimethylene cycloaddition (see Trost et ai, J. Am. Chem. Soc., 1991,113, 9007) of diacetone D-galacto-... 

---