Methyl 2-isocyanoacetate

The mechanism of the condensation in Part D probably involves thioformylation of the metallated isocyanoacetate followed by intramolecular 1,1-addition of the tautomeric enethiol to the isonitrile. This thi2izole synthesis is analogous to the formation of oxazoles from acylation of metallated isonitriles with acid chlorides or anhydrides. " Interestingly, ethyl formate does not react with isocyanoacetate under the conditions of this procedure. Ethyl and methyl isocyanoacetate have been prepared in a similar manner by dehydration of the corresponding N-formylglycine esters with phosgene and trichloromethyl chloroformate, respectively. The phosphoryl chloride method described here was provided to the submitters by Professor U. Schollkopf and is based on the procedure of Bohme and Fuchs. The preparation of O-ethyl thioformate in Part C was developed from a report by Ohno, Koi/.uma, and Tsuchihaski. " ... 

Methyl isocyanoacetate See Methyl isocyanoacetate Heavy metals See other metal oxonon-metallates, reducants... 

Methyl isocyanoacetate is known to react with such electron deficient alkenes under basic conditions to give 2-carboalkoxy pyrroles (6) via... 

The asymmetric aldol reaction of a-ketoesters (RCOCOOMe R=Me, z-Bu, Ph) with methyl isocyanoacetate or A,A-dimethyl-isocyanoacetamide in the... 

In addition, interest in combinatorial chemical applications led a team at AMGEN to the recognition of a related but different pathway which afforded tetrahydro tetrazolo[l,5-zz]pyrazine-6-ones 121 (Scheme 22) <2000TL8729>. In this procedure, three starting components, that is, the ketone, the primary amine, and trimethylsilyl azide, as in the previous method, were used, and the fourth component was methyl isocyanoacetate. This reaction also took place under relatively smooth conditions (methanolic solution at room temperature for 6h followed by reflux for 24 h) to yield the products 121 in good to high yields. The reaction obviously proceeds by the formation of intermediate 120. 

Asymmetric aldol reaction. In the presence of a gold(I) complex (1) and a chiral ferrocenylphosphine (2), various aldehydes react with methyl isocyanoacetate... 

Methyl isocyanoacetate, 1470 /V-Mcthylmorpholinc oxide, 1997 Nickel, Hydrogen, Oxygen, 4820 Nitric acid, Sulfur dioxide, 4436... 

A library of piperazine containing fused azepine-tetrazoles 183 was built by Nixey et al. via Ugi reaction in the solution phase [55]. This library comprises an example of a building block introduced piperazine (Scheme 32). The reaction of A-Boc-a-amino aldehyde 184, methyl isocyanoacetate 185, substituted piperazines 186, and trimethylsilylazide 181 in methanol, followed by acid treatment, proton scavenging, and reflux affords bicyciic azepine-tetrazoles 183. This efficient protocol with three diversity points can be used to generate arrays of biologically... 

A library of fused tetrazole-ketopiperazines 187 was obtained by Nixey et al. via Ugi four-component reaction in the solution phase [56]. The reaction of an oxo component 188, primary amine 189, methyl isocyanoacetate 190, and trimethylsi-lylazide 181 in methanol at reflux affords bicyclic tetrazole-ketopiperazines 187 in good yield (Scheme 33). The cyclization to afford the tetrazole-ketopiperazines is performed spontaneously under the reaction conditions. 

Bienayme34 reported the formation of substituted isonitriles by treatment of a dialkyl amine with imidazole diethylacetal and methyl isocyanoacetate. This forms dialky-lamino propenoates via a three-component cascade reaction mechanism (Scheme 5.18). 

Reaction of methyl isocyanoacetate with methyl 2-formylbenzoate in the presence of sodium hydride in DMF at 30-40°C gives methyl 1-oxo-l,2-dihydroisoquinoline-3-carboxylate in 42% yield. 

Metkoxycarbonyloxazoles. Condensation of carboxylic acids with methyl isocyanoacetate in the presence of K2C03 and DPPA (1 equiv.) leads to 5-substituted 4-methoxycarbonyloxazoles. Racemization is only slight when this C-acylation is applied to Boc-amino acids.1... 

Workers at Amgen further exploited this reaction in an attempt to access 6,5-fused ketopiperazine-tetrazoles 96 and 7,5-fused azepine-tetrazoles 94, respectively (Scheme 12). Thus, reaction of methyl-isocyanoacetates 92,... 

Typical Experimental Procedure (Scale Up). The following procedure was followed for the large-scale preparation of 99 Solutions of N-(tert-butoxycarbonyl)-D-prolinal (0.1 M, 10 ml in MeOH), l-(2-pyrimidyl) piperazine (0.1 M, 10 ml in MeOH), methyl isocyanoacetate (0.1 M,... 

Methylimidazole, 1495 Methyl iminioformate chloride, 0893 Methyl iodide, see Iodomethane, 0444 f Methyl isobutyrate, 1970 f Methyl isocyanate, 0758 Methyl isocyanide, 0756 Methyl isocyanoacetate, 1466... 

The neutral and cationic [Pd(II)NCN] pincer-containing dendritic assemblies 14 and 15 have been used as Lewis acid catalysts in the aldol condensation of benzaldehyde and methyl isocyanoacetate. These showed conversions, turnover frequencies and cis/trans ratios of the oxazoline products that were essentially identical to those of the monomeric model complex applied in the same reaction. 

Several 2-substituted 3,4-diarylpyrroles 3 have been prepared in a regioselective process employing the base induced addition of methyl isocyanoacetate to the a,f -unsaturated nitriles 4, and one of the pyrroles so obtained was used in a concise synthesis of the alkaloid ningalin B... 

Table 3. Diastereo- and enantioselective aldol reaction of methyl isocyanoacetate (27) with tildehydes catalyzed by chiral ferrocenylphosphine 86c gold(I) complex.

Ito and coworkers found that chiral ferrocenylphosphine-silver(I) complexes also catalyze the asymmetric aldol reaction of isocyanoacetate with aldehydes (Sch. 26) [51]. It is essential to keep the isocyanoacetate at a low concentration to obtain a product with high optical purity. They performed IR studies on the structures of gold(I) and silver(I) complexes with chiral ferrocenylphosphine 86a in the presence of methyl isocyanoacetate (27) and found significant differences between the iso-cyanoacetate-to-metal coordination numbers of these metal complexes (Sch. 27). The gold(I) complex has the tricoordinated structure 100, which results in high ee, whereas for the silver(I) complex there is an equilibrium between the tricoordinated structure 101 and the tetracoordinated structure 102, which results in low enantioselectivity. Slow addition of isocyanoacetate 27 to a solution of the silver(I) catalyst and aldehyde is effective in reducing the undesirable tetracoordinated species and results in high enantioselectivity. 

Ruthenium(ll)-catalyzed cycloaddition reactions of Y-sulfonylimines 1308 with methyl isocyanoacetate 1309 gave /ra r-2-imidazolines 1310 stereoselectively in 75-90% yields under neutral, mild conditions [R = phenyl, substituted phenyl, 2-furyl, lrans-PhCH=CH, tert-Bu R = tosyl, PI1SO2] (Scheme 333) < 1997JOG1799>. In contrast, the same reaction catalyzed by 1 mol% AuCl(( -HexNG) provides 4-methoxycarbonyl-5-alkyl-2-imidazolines 1321 with over 98% -selectivity (Scheme 333) <1996TL4969>. 

For the aldol reaction of small alkyl aldehydes such as acetaldehyde, the enantioselectivity is improved by the use of Ar,A -dialkyl-oe-isocyanoacetamides instead of isocyanoacetate esters (Scheme 2-54) [76]. For example, the reaction of acetaldehyde with AT,iV-dialkyl-a-isocyanoacetamides 64 in the presence of R)- S)-8g/gold catalyst gives the corresponding /ranj-oxazoline 65 of 99% ee, which is much higher than the enantioselectivity (85% ee) observed in the reaction with methyl isocyanoacetate under the same reaction conditions. 

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