Diazoacetate, synthesis with

Diazocarbonyl compounds are especially useful in these reactions because of their ease of formation, relative stability, and controlled reactivity in catalytic reactions [ 1,11 ]. As outlined in Scheme 1, a wide diversity of methodologies are available for this synthesis, with access dependent on the nature of Z. Vinyl- and aryldiazoacetates are accessible by other pathways [2]. The order of reactivity toward diazo decomposition has diazoketones and diazoacetates much more reactive than diazoacetoacetates or diazomalonates. However, the influence of electronic effects on reactivities is more pronounced with phenyl- and vinyl-diazoacetates than with diazoacetoacetates and, especially, diazoacetates [12]. 

Asymmetric synthesis of 2,5-dimethyl-2,4-hexadiene (28) and /-menthyl diazoacetate (29) with chiral copper complexes (30) was successfully conducted by Aratani et al. [13] to afford the (1 A)-chrysanthem ic acid /-menthyl ester (31) in high optical and chemical yield. Since this finding, a lot of chiral copper complexes have been reported and applied to the asymmetric synthesis of (IR)-chrysanthemate. However, these copper complexes required more than 1 mol% of the catalyst and the cis/trans ratio still remains unsatisfactory. Moreover, /-menthyl ester was crucial for the high enantioselectivity. Given an industrial production of... 

Reviews (a) V. Dave and E. W. Wamhoff, The Reactions of Diazoacetic Esters with Alkenes, Alkynes, Heterocyclic and Aromatic Compounds, in W. G. Dauben, ed., Organic Reactions, Vol. 18, Chap. 3, John Wiley Sons, New York, 1970. (b) G. Maas, Top. Curr. Chem., 137, 75 (1987). (c) J. Salaun, Chem. Rev., 89, 1247 (1989). (d) A. Demonceau, A. J. Hubert, and A. F. Noels, Basic Principles in Carbene Chemistry and Applications to Organic Synthesis, in A. F. Noels, M. Graziani, and A. J. Hubert, eds., Metal Promoted Selectivity in Organic Synthesis, p. 237, Kluwer Academic, Dordrecht, 1991. 

A. J. Hubert, A. F. Noels, A. J. Anciaux, and Ph. Teyssie (1976) Rhodium(II) carboxylates novel highly efficient catalysts for the cyclopropanation of alkenes with alkyl diazoacetates, Synthesis 9 600-602... 

The idea of matching individual diazoacetate enantiomers with a particular chiral dirhodium (II) has been very successfully exploited by Doyle s group to optimize diastereocontrol and regiocontrol in product formation. The behavior of the individual enantiomers of ds-2-methylcyclohexyl diazoacetate, Eq. (47) provides an illustrative example of the power of this approach in regioselective synthesis. Whereas the (lS,lR)-enantiomer of (41) forms the all ds-bicyclic lac-... 

In 1998, Hossain et al. reported the catalytic synthesis of aziridines, using an achiral iron Lewis acid-THF adduct, [CpFe(CO)2(THF)]+[BF4] (108). The reaction was generally ds-aziridine selective. With this approach, cis selectivity is now known to be typical, since most catalytic reactions mainly yield ds-aziridine. In 2001, they continuously reported the reason for the apparent cis-aziridine selectivity in the reaction of ethyl diazoacetate (10) with JV-benzylidene aniline (109a), catalyzed by (108) [36]. The catalytic reaction produces both cis- and trans-aziridines. Once... 

Maas and coworkers have also reported preparation of q -[(2-alkynyloxylsilyl-a-diazoacetates (80-83) for screening copper-and rhodium-mediated carbenoid reactions (eq 20). Treatment of diazoacetate 80 with catalytic amounts of copper(I) triflate gave a mixture of compounds from which the nitrogen-free oxasilaheterocycles 85 and 86 were isolated in low yields (eq 21). Maas and coworkers have prepared novel diazoacetates bearing an aminosilyl substituent that show remarkable thermal stability. In yet another communication, the authors report synthesis of (diazomethyl)-silyl functionalized Fisher-type carbene conplexes (eq 22)P... 

Steinkopf and Augestad-Jensen in 1922 reported the reaction of diazoacetic ester with thiophene and the hydrolysis of the adduct (10) to an acid, m.p. 107°, of unknown identity. Pettit has used this adduct in the synthesis of the thiapyrylium cation (10->11 12). The same adduct (10) was obtained by photolysis of diazoacetic ester... 

The history of 1,3-dipoles began in the nineteenth century, when Curtius reported on the diazoacetic ester. A few years later, Buchner et al successfully performed the first 1,3-dipolar cycloaddition of the diazoacetic ester with a,j8-unsaturated esters. Despite the fact that, over the subsequent years, different 1,3-dipoles have been discovered, only a few have been generally effective in organic synthesis, e.g. the well-known Diels-Alder reaction. ... 

The potent dopamine reuptake inhibitor (-l-)-indatraline 7 was prepared in a few steps after the reaction of methyl (3,4-dichlorophenyl)diazoacetate 9 with an excess of 1,4-cyclohexadiene, which was used as a synthetic equivalent of a phenyl group, in the presence of a catalytic amount of Rh2(5 -DOSP)4. The product 11 was isolated in a good yield and a high enantiomeric excess. Finally, 7 was obtained in 99% ee after recrystallization. The synthesis of (+)-cetiedil 8, an effective K channel blocker, was carried out in a similar approach. The enantioselective C—H insertion of... 

Synthesis of aziridines by treatment of carbenes with imines was reported by Jacobsen [56]. A metallocarbene 104 derived from ethyl diazoacetate and copper fluorophosphate was treated with N-arylaldimines to form aziridines with reasonable diastereoselectivities (>10 1 in favor of cis) but with low enantioselectivities (about 44% ee). This was shown to result from a competitive achiral reaction path-... 

Probably the most widely applicable asymmetric imine aziridination reaction reported to date is that of Wulff et al. These workers approached the reaction from a different perspective, utilizing the so-called vaulted , axially chiral boron Lewis acids VANOL and VAPOL [35] to mediate reactions between ethyl diazoacetate and N-benzhydrylimines (Scheme 4.29) [36]. The reactions proceed with impressive enantiocontrol, but there is a requirement that the benzhydryl substituent be present since this group is not an aziridine activator there is, therefore, a need for deprotection and attachment of a suitable activating group. Nonetheless, this method is a powerful one, with great potential for synthesis, as shown by the rapid synthesis of chloroamphenicol by the methodology [37]. 

With nonracemic chiral diazoacetates the insertion process occurs with evident match/mismatch characteristics. This has been demonstrated in reactions of optically pure 2-methylcyclohexyl diazoacetates (Eq. 9) [85] and in carbon-hydrogen insertion reactions of steroidal diazoacetates (Eq. 10) [86], as well as with the synthesis of pyrrolizidines 36 and 37 [84]. The mechanistic preference for formation of a /J-lactone in Eq. 10 over insertion into the 4-position is not clear,but there are other examples of /J-lactone formation [87]. In these and related examples, selectivities in match/mismatch examples are high, and future investigations are anticipated to show even greater applicability. 

Carbenoid N-H insertion of amines with diazoacetates provides a useful means for the synthesis of ot-amino esters. Fe(III) porphyrins [64] and Fe(III/IV) corroles [65] are efficient catalysts for N-H carbenoid insertion of various aromatic and aliphatic amines using EDA as a carbene source (Scheme 16). The insertion reactions occur at room temperature and can be completed in short reaction times and with high product yields. It is performed in a one-pot fashion without the need for slow... 

Rearrangement of an intermediary S-ylide is the key step of a synthesis of 142 from the 6-phenylthiomethyl-2-pyrone 140 and ethyl diazoacetate in the presence of a catalytic amount of Cu(acac)2 158>. The primary rearrangement product 141 is smoothly isomerized to 142 by treatment with silica gel. 

Methyl diazoacetate is also decomposed on Raney nickel to give quantitatively a mixture of dimethyl fumarate and maleate 369) N2 evolution is observed even at room temperature. Most remarkably, dimethyl maleate is formed with high stereoselectivity (at 70 °C 92% of dimethyl maleate, 7% of dimethyl fumarate 370)). This represents one of the few cases of stereoselective synthesis on metal surfaces which have been found so far. 

This sequence illustrates a very general method for the synthesis of methyl y-oxoalkanoates which are valuable intermediates in organic synthesis.3 6 The scope of the cyclopropanation reaction is very broad only functional groups interacting with the carbenoid generated from melhyl diazoacetate are not compatible. Use of Rh2(OAc)4 instead of Cu(acac)2 as catalyst did not afford better yields.3 The cyclopropanation reaction has been performed with similar efficiency on scales from 4 mmol up to 500 mmol. 

Perhaps the earliest reported method for the synthesis of the 1,2,3-thiadiazole ring system was the one described by Pechmann and Nold in which diazomethane was reacted with phenyl isothiocyanate. Of the four possible isomers that could be obtained from the reaction, 5-anilino-l,2,3-thiadiazole 62 (R1 Ph, R2 = H) was the only product formed (Equation 16) <1896CB2588>. This method continues to be used as a route to 5-amino substituted 1,2,3-thiadiazoles. 4,5-Disubstituted 1,2,3-thiadiazoles have been produced in excellent yield by reaction of l,l -thiocar-bonyl diimidazole with ethyl diazoacetate <1988SUL155>. 

The synthesis of 1,2,3-selenadiazole derivatives has been reported. The reaction of aroyl chlorides such as 102 with potassium isoselenocyanate and ethyl diazoacetate yielded 5-(aroylimino)-2,5-dihydro-l, 2,3-selenadiazole-4-carboxylate esters such as 104. A reaction mechanism via the initial formation of the corresponding aroyl isoselenocyanate 103 followed by a 1,3-dipolar cycloaddition of the diazo compound with the C=Se bond is proposed <00HCA539>. 

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