Ethyl 2-diazoacetate reaction with

Alkylation of acetylacctone chelates is generally unsuccessful, but carbon—methylene bonds can be formed by chloromethylation, reaction with ethyl diazoacetate,reaction with thioacetals (equations 64, 65 and 66) and by the Mannich reaction (Scheme 73). The Mannich base can be quatemized with methyl iodide and converted by cyanide ion into a cyanomethyl-substituted chelate. 

From Diazo Compounds via 1,3-Dipolar Cycloaddition. This method has been utilized widely in heterocychc chemistry. Pyrazohne (57) has been synthesized by reaction of ethyl diazoacetate (58) with a,P-unsaturated ester in the presence of pyridine (eq. 12) (42). 

The normal electron-demand principle of activation of 1,3-dipolar cycloaddition reactions of nitrones has also been tested for the 1,3-dipolar cycloaddition reaction of alkenes with diazoalkanes [71]. The reaction of ethyl diazoacetate 33 with 19b in the presence of a TiCl2-TADDOLate catalyst 23a afforded the 1,3-dipolar cycloaddition product 34 in good yield and with 30-40% ee (Scheme 6.26). 

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],... 

The reaction of ethyl diazoacetate (312) with sodium or potassium ethoxide was studied by Curtius and his coworkers (08CB3140). They isolated a compound for which they proposed structure (316), which is a metal salt of diethyl l,6-dihydro-l,2,4,5-tetrazine-3,6-dicarboxy-late complexed with one mole of the ethoxide used. 

Compared with results obtained for ethyl diazoacetate, reactions of diazomethane with allyl bromide produce a dramatic reversal in the relative reactivities of the carbenoid species towards the nucleophilic bromide and the carbon-carbon double bond. These results are in accord with a greater electrophilic selectivity of the dialkoxycarbonyl carbenoid intermediate relative to the ethoxycarbonyl carbenoid. That increasing the electrophilicity of the carbenoid intermediate can reverse its reactivity towards the nucleophilic heteroatom relative to the olefin is consistent with the nature of this... 

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],... 

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 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). 

In view of this we have tested several heterogeneous copper catalysts in the benchmark reaction of ethyl diazoacetate (1) with styrene (2). Some of them have been also used in the reactions of ethyl diazoacetate (1) with cyclohexene (4), a-methylstyrene (6), trans-anethole... 

The catalysts leading to the higher trans and cis preferences, namely Cu(II)-bentonite and Cu(II)-K10, were tested in the reactions of ethyl diazoacetate (1) with different alkenes (Scheme 2). The results obtained (Table 2) show that the yield and the selectivities with regard to both reagents increase with the electron-donor ability of the substituents of the double bond, which indicates the electrophilic character of the reaction. Therefore the cyclopropanes coming from chalcone (10) could not be obtained. 

Table 2. Results obtained in the reactions of ethyl diazoacetate (1) with several alkenes in...

Reaction with trialkyIhoranes.14 Ethyl diazoacetate reacts with trialkylboranes with loss of nitrogen to give, after hydrolysis, the homologated ethyl ester ... 

Reaction of ethyl diazoacetate with sr-allylnickel bromide (2, 291). Ethyl diazoacetate reacts with 7r-allylnickel bromide (0°, ether) with evolution of nitrogen to give ethyl tranr-/3-vinylacrylatc (69% yield), ethyl cw-/3-vinylacrylate (19% yield), and ethyl A4-pentenoate (8% yield).1 A possible mechanism is suggested based on... 

The reaction of ethyl diazoacetate (4) with 4-vinylpyridine (5) to yield ethyl 4-(2-carbethoxycyclopropyl)pyridine (6) (69) (Scheme 2) was correctly predicted by CAMEO using the Carbenoid module however, this reaction, which was reported in the literature to proceed when heated, was found to "proceed" in CAMEO only when ultraviolet light was selected to initiate the reaction. In addition, an unusual and seemingly unlikely 4-vinyldihydropyridine product (7) was also predicted (Scheme 2). 

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... 

In the reaction of Ph3P=C=C=X with tosyl azide, [3 + 2] cycloadducts are obtained. In a similar manner ethyl diazoacetate reacts with Ph3P =C=NPh to give the mesoionic... 

Ethyl 2,4,7-triaryl-l,3-oxazepine-6-carboxylates 15 are formed in modest yield by the reaction of ethyl diazoacetate with 1,3-oxazinium perchlorates 14.13... 

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-... 

Reactions between imines and a-diazo carboxylates afford aziridine-2-carboxylates [55]. An asymmetric version of this reaction using chiral nonracemic catalysts has been described [53, 56-58]. As an example, catalytic aziridination of inline 44 (Scheme 3.14) with ethyl diazoacetate in the presence of 10% catalyst generated... 

The BF3 Et20-catalyzed aziridination of compounds 47 (Scheme 3.15) with a diazo ester derived from (R)-pantolacetone gave aziridine-2-carboxylates 48 [59]. The reaction exhibited both high cis selectivity (>95 <5) and excellent diastereose-lectivity. Treatment of a-amino nitrile 49 (Scheme 3.16) with ethyl diazoacetate in the presence of 0.5 equivalent of SnCl4 afforded aziridines 50 and 51 in 39% yield in a ratio of 75 25 [60]. 

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