Cyclic reaction with diethyl malonate

The alcohol 470 was prepared from the mesylate 469 by reaction with diethyl malonate followed by reduction to give 470, whose selective acetylation was carried out by reaction with trimethyl orthoacetate followed by acid hydrolysis of the cyclic orthoester intermediate. Bromination and then coupling gave 471 [88JCS(P1)2757]. 

In a series of publications (75JOC2600, 70JOC1965, 73JOC3087), Potts and coworkers have reported that cyclic amidines (290) readily condense with trichloromethylsulfenyl chloride (329) to yield the sulfenamides (330 Scheme 119). Treatment of the latter compounds with aromatic amines in the presence of triethylamine results in cyclization, possibly via an intermediate such as (331), to produce bicyclic products of type (332). Heterocycles (290) which have been used successfully in this reaction include 2-amino-l,3,4-thiadiazoles, 3-aminopyridazines, 2-aminopyrimidines, 2-aminopyrazines, 2-aminopyridines, 3-aminoisoxazoles and 5-amino-1,2,4-thiadiazoles. The sulfenamide derivative (330) of 2-aminopyridine also was found to react with sodium sulfide and with diethyl malonate to produce (333) and (334) respectively. Attempts to hydrolyze (332) to (295) under acidic conditions failed. 

Chiral allylic cyclic carbonates such as 551 or 552 undergo excellent regioselective alkylation reactions with soft nucleophiles in the presence of palladium(O) in refluxing THF to provide ( )-allylic alcohols. The reaction of 4-0-benzyl-2,3-isopropylidene-L-threose (167) with the appropriate ylid, followed by deprotection of the isopropylidene ring with acidic resin and cyclic carbonate formation, provides a good overall yield of either 551 or 552. Ring opening with diethyl malonate in the presence of tetrakis(triphenylphosphine)palladium(0) provides in excellent yield the allylic alcohols 553 or 554, where the diastereoselectivity exceeds 99%. This reaction represents an efficient method of 1,3-chirality transfer [180] (Scheme 122). 

There are very few precedents for the reaction of cyclic a-halo ethers with carbanions. Zelinski and coworkers114 and Schudel and Rice115 reported the preparation of diethyl DL-tetrahydropyran-2-ylmalonate (137) by treatment of 2-bromo- or 2-chloro-tetrahydropyran (136) with diethyl sodiomalonate. The product was subsequently converted into the malonic and acetic acid derivatives, 138 and 139, respectively. The same sequence has also been reported by other workers.116... 

Treatment of diethyl malonate and related compounds with 1,2-dihaloethane in the presence of base constitutes a classical method of cyclopropane synthesis296"300. The reaction can be conveniently carried out under PTC conditions. An improved method utilizing solid-liquid phase transfer catalysis has been reported298. The reaction of dimethyl or diethyl malonate with 1,2-dibromoalkanes except for 1,2-dibromethane tends to give only low yields of 2-alkylcyclopropane-l, 1-dicarboxylic esters. By the use of di-tm-butyl malonate, their preparations in satisfactory yields are realized (equation 134)297. The 2-alkylcyclopropane derivatives are also obtained from the reaction of dimethyl malonate and cyclic sulfates derived from alkane-1,2-diols (equation 135)301. Asymmetric synthesis... 

In the case of 1,3-dicarbonyl compounds, the solvent frequently interferes with the coupling reaction. So with diethyl sodio malonate in ethanol [212b], methanol [212b], dimethylacetamide [212b], or HMPTA [216], besides the dimer and the trimer, the compounds LIXa-c are obtained. They are presumably formed by oxidation of the solvent to the aldehyde and its condensation with the active methylene compound. No dimer was detected in the oxidation of sodio acetoacetate in ethanol, with the major product being LX [217]. Anodic oxidation of cyclic 1,3-diketones in aqueous methanolic sodium hydroxide does not yield the dimer but product LXI, formed by condensation of the starting compound with formaldehyde [218]. 

This type of reaction is not limited to cyclic ketones. Tertiary a-bromo ketones, such as 17 and 19, react with diethyl sodiomalonate in tetrahydrofuran with formation of the cyclopropanols 18 and 20 in 42-56% yield. Surprisingly, conversion of these aliphatic compounds required reflux instead of the milder conditions employed for the cyclic analogs. On the contrary, a-halo ketones possessing a primary or secondary carbon at the a-position afforded the substitution products, e.g. l-bromo-3-methylbutan-2-one (21) yielded the substituted malonate 22 in 81% yield. ... 

Quinoxaline-2-carboxaldehyde has been converted into the 2-carboxylic acid by oxidation with potassium permanganate in acetone and reduced to the 2-hydroxymethyl compound by treatment with formalin and potassium hydroxide. It also undergoes other typical reactions of aromatic aldehydes such as benzoin formation on reaction with potassium cyanide - and condensation reactions with malonic acid and its diethyl ester and Schiff base formation. Acid-catalyzed reaction of quinoxaline-2-carboxaldehyde with ethylene glycol gives the cyclic acetal the diethylacetal has been prepared by reaction of 2-dibromomethylquinoxaline with sodium ethoxide. " An indirect preparation of the oxime 11 is achieved by treatment of 2-nitromethyl-quinoxaline (10) with diazomethane followed by thermolysis of the resulting nitronic ester. 

Blocked isocyanates permit making coatings that are stable at ambient temperature when baked, the monofunctional blocking agent is volatilized and the coreactant is cross-linked. An extensive review of blocked isocyanates, their reactions, and uses is available (127). The blocking agents most widely used are phenols, oximes, alcohols, e-caprolactam (hexahydro-2ff-azepin-2-one) [105-60-2], 3,5-dimethylpyrazole, 1,2,4-triazole, and diethyl malonate (propanedioic acid diethyl ester) [105-53-3]. A variety of catalysts are used DBTDL is most widely used but many other catalysts have also been used. Bismuth tris(2-ethyl hexanoate) has been particularly recommended (128). In electrodeposition primers, DBTDL has insufficient hydrolytic stability, and tributyltin oxide is an example of an alternate catalyst (129). Cyclic amidines, such as l,5-diazabicyclo[4.3.0]non-5-ene, are reported to be superior catalysts for use with uretdione cross-linkers in powder coatings (130). 

The reaction of cyclic oxonium derivatives of polyhedral boron hydrides with acetamido diethyl-malonate (glycine anion equivalent for amino acid synthesis), a variation of the classical Sdrensen synthesis of amino acids, followed by acidic hydrolysis and decarboxylation was proposed as a route to boron hydride-based aminoacids (Figure 24.10) [31,51]. 

As diazocarbonyl compounds bearing a substituent other than H on the diazobearing carbon, some cyclic diazoketones were applied to the Pd-mediated polymerization. The a,j3-unsaturated cyclic diazoketone 6 derived from cyclohexenone can be transformed into polymers with a unique structure, where the main chain carbon is one of carbon atoms of a six-membered ring [45] (Scheme 23). In addition, the C=C bond conjugated with C=0 would be directed outward from the main chain, which may render an attack of nucleophiles (1,4-conjugate addition) feasible. As expected, the addition of nucleophiles such as organolithium and sodium salt of diethyl malonate occurred by the reaction with the polymer. 

By comparing with the alkali metal free La-BINOL catalyst, the (/ )-LSB-catalyzed Michael reactions of malonate to cyclic enone proceeded smoothly with high enantioselectivities even at room temperature. The reaction between 2-cyclohexen-l-one and dibenzyl methylmalonate completed in 12 hours at room temperature to afford adduct in 96% yield and 90% ee. When dimethyl malonate was used, 98% yield with 83% ee of the product was obtained. Switching the dimethyl analog diethyl malonate also furnished similar product yield and enantioselectivity (97% yield and 81% ee). 

In subsequent studies, the scope of the Heck reaction/ anion-trapping cascade was further extended using soft car-banionic nucleophiles as illustrated in the asymmetric synthesis of (—)-D -capnellene 17. Treatment of prochiral vinyl triflate 15 with Pd(OAc>2, (5)-BINAP, and NaBr, as weU as the sodium enolate of diethyl (2-((rert-butyldiphe-nylsilyl)oxy)ethyl)malonate, gave the cyclic product 16 in 87% ee and 77% yield as the sole product. The use of NaBr as an additive improved the optical yields and was critical in preventing counteranion exchange between the triflate anion and the enolate anion by complexing with sodium enolate (Scheme 13.6). Compound 16 was then advanced through several steps to complete the total synthesis (—)-D -capnellene 17. 

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