Carbonyl compounds with diazomethane

B. CYCLOPROPANATION OF a,j8-UNSATURATED CARBONYL COMPOUNDS WITH DIAZOMETHANE... 

TABLE 1. Cyclopropanation of a,/3-unsaturated carbonyl compounds with diazomethane... 

Attempts to carry out carbene transfer reactions with chiral palladium catalysts were unsuccessful so far. Demnark et al. conducted a detailed study in which cyclopropana-tions of a,/3-unsaturated carbonyl compounds with diazomethane catalyzed by bis-(oxazoline)palladium(n) complexes were investigated. Virtual no asymmetric induction was obtained in these reactions which led to the conclusion—especially in light of the excellent asymmetric enviromnent bis(oxazolines) metal complexes offer in general—-that partial or complete ligand dissociation must have been occurred during the course of the reaction. 

Partially and perfluorinated thioketones and thioaldehyde were stabilized as anthracene adducts (70). The adducts (70) were prepared in moderate yield from the corresponding carbonyl compounds with P4S10 or Lawesson s reagent in the presence of anthracene under toluene reflux. The generated thiocarbonyl compounds are not accessible in bulk due to their tendency towards polymerization. By thermolysis of the anthracene adducts (70) in the presence of C,N-bis(triisopropylsilyl)nitrilimine (NI), 1,3,4-thiadiazole derivatives (71) were obtained. Also, 1,3-dipolar cycloaddition with bis(trimethylstannyl)diazomethane (BTSD) to give consecutive products (72) from a 1,2-metallotropic migration of primary adducts was discussed. [95LA95]... 

Apart from routine applications to cyclopropane synthesis,the application of new catalysts to the decomposition of diazo-compounds has received considerable attention. The use of palladium acetate, originally reported in 1972 by Paulissen et o/., has been extended and applied to diazomethane and ethyl diazoacetate in the presence of aP-unsaturated carbonyl compounds. With a- and a-substituted aP-unsaturated ketones, stereospecific cis-addition occurs in excellent yields, but the catalyst proves to be ineffective with analogous trisubstituted olefins, as illustrated for the formation of (110) with diazomethane. The use of palladium chloride with the... 

These compounds generally exist in carbonyl forms. The oxygen function can be converted into halogen by phosphorus halides. Reactions with electrophiles are quite complex. Thus urazole (511) reacts with diazomethane quickly to yield (512), which is more slowly converted into (513). 1-Phenylurazole gives (514) however, 4-phenylurazole yields (515). Oxadiazolinones of type (516) can be alkylated at both O- and N-atoms. 

In general, reaction of diazomethane with a, -unsaturated carbonyl compounds affords pyrazolines in which the nucleophilic methylene group is attached to the carbon atom of the carbonyl compound. According to Huisgen, the reactions belong to the general class of 1,3-dipolar cycloadditions. 

Palladium(II) acetate was found to be a good catalyst for such cyclopropanations with ethyl diazoacetate (Scheme 19) by analogy with the same transformation using diazomethane (see Sect. 2.1). The best yields were obtained with monosubstituted alkenes such as acrylic esters and methyl vinyl ketone (64-85 %), whereas they dropped to 10-30% for a,p-unsaturated carbonyl compounds bearing alkyl groups in a- or p-position such as ethyl crotonate, isophorone and methyl methacrylate 141). In none of these reactions was formation of carbene dimers observed. 7>ms-benzalaceto-phenone was cyclopropanated stereospecifically in about 50% yield PdCl2 and palladium(II) acetylacetonate were less efficient catalysts 34 >. Diazoketones may be used instead of diazoesters, as the cyclopropanation of acrylonitrile by diazoacenaph-thenone/Pd(OAc)2 (75 % yield) shows142). 

It was important to determine whether the fluorine atom must be attached directly to the phosphorus atom in order to produce phosphorofluoridate-like activity. For this purpose we treated the toxic di-sec.-butyl phosphorofluoridate1 with diazomethane and obtained a compound which was undoubtedly di- ec.-butyl fluoromethylphosphonate (XIX). Unlike the parent phosphorofluoridate, the fluoromethylphosphonate was only slightly toxic and produced negligible myosis. (It may be mentioned here that thionyl chloride and carbonyl chloride were converted by means of diazomethane into bis-(chloromethyl)-sulphoxide and S-dichloroacetone respectively.)... 

The chemical behavior of heteroatom-substituted vinylcarbene complexes is similar to that of a,(3-unsaturated carbonyl compounds (Figure 2.17) [206]. It is possible to perform Michael additions [217,230], 1,4-addition of cuprates [151], additions of nucleophilic radicals [231], 1,3-dipolar cycloadditions [232,233], inter-[234-241] or intramolecular [220,242] Diels-Alder reactions, as well as Simmons-Smith- [243], sulfur ylide- [244] or diazomethane-mediated [151] cyclopropanati-ons of the vinylcarbene C-C double bond. The treatment of arylcarbene complexes with organolithium reagents ean lead via conjugate addition to substituted 1,4-cyclohexadien-6-ylidene complexes [245]. 

Bis-acceptor-substituted diazomethanes are most conveniently prepared by diazo group transfer to CH acidic compounds either with sulfonyl azides under basic conditions [949,950] or with l-alkyl-2-azidopyridinium salts [951] under neutral or acidic conditions [952-954]. Diazo group transfer with both types of reagents usually proceeds in high yield with malonic acid derivatives, 3-keto esters and amides, 1,3-diketones, or p, y-unsaturated carbonyl compounds [955,956]. Cyano-, sulfonyl, or nitrodiazomethanes, which can be unstable or sensitive to bases, can often only be prepared with 2-azidopyridinium salts, which accomplish diazo group transfer under neutral or slightly acidic reaction conditions. Other problematic substrates include amides of the type Z-CHj-CONHR and P-imino esters or the tautomeric 3-amino-2-propenoic esters, which upon diazo group transfer cyclize to 1,2,3-triazoles [957-959]. 

Tropone itself gives with diazomethane a 3 1 mixture of 1- and 2-methylcycloheptapyrazol-4-ones (143a,b), along with cyclooctatrienone and 2,3-homotropone (72TL1925). Here the regiochemistry of cycloaddition is the reverse of that of diazomethane with simple a,/3-unsaturated carbonyl compounds (80MI1, p.282). The different behavior of tropone and, e.g.. 

The elucidation of the hydroxypyrazine-pyrazinone tautomerism has been made using spectral methods. An IR spectral analysis focuses on the carbonyl absorption of the amide group in the keto tautomer. A more useful method is UV spectroscopy, that is, the objective structure in solution is easily estimated by comparison with the UV spectra of bond-fixed compounds related to the two tautomers, namely O-methylated and N-methylated derivatives 9 and 10, which are prepared by methylation of the hydroxypyrazines or pyrazinones with diazomethane (Scheme 1). The above two investigations were achieved by this methodology. 

Electron-withdrawing substituents generally increase diazo compounds stability toward decomposition. Dicarbonyl diazomethane, which bears two carbonyl groups flanking the diazomethane carbon, are more stable than diazo compounds with only one carbonyl substituent. In general, metal catalysed decomposition of dicarbonyl diazomethane requires higher temperature than does monocarbonyl substituted diazomethane. As indicated before, rhodium(II) carboxylates are the most active catalysts for diazo decomposition. With dicarbonyl diazomethane, the rhodium(II) carboxylate-promoted cyclopropanation process can also be carried out under ambient conditions to afford a high yield of products. 

When phenyl(trimethylsilyl)diazomethane (20) is pyrolyzed in the gas phase, typical reactions of carbene 21 can be observed (see Section III.E.4). However, copyrolysis with alcohols or carbonyl compounds generates again products which are derived from silene 2239,40 (equation 6). Thus, alkoxysilanes 23 are obtained in the presence of alcohols and alkenes 24 in the presence of an aldehyde or a ketone. 2,3-Dimethylbuta-l,3-diene traps both the carbene (see Section ni.E.4) and the silene. 

The intermediacy of such oxaspiropentanes has been proposed in the addition of diazomethane to ketonesi0) and in the reaction of dimethyloxosulfonium methylide with a-haloketones55). In contrast to phosphorous ylides, sulfur ylides usually condense with carbonyl compounds to yield epoxides, thus reaction of the N,N-dimethylaminophenyloxosulfonium cyclopropylide 99 with cyclohexanone produced the dispiroepoxide 100 which rearranged to the spiro [3.5] nonan-l-one 101 upon isolation by gas chromatography, Eq. (29) S6). 

Fluorinated cz/kunsaturated carbonyl compounds acting as dipolarophiles react with diazomethane, giving 1,3-dipolar cycloaddition products with high regioselectivity (76T1995, 00IZV1770). 

Azomethines (Schiff bases) have been prepared in order to block the amino group, using different carbonyl compounds as reagents. Aqueous formaldehyde condenses with amino acids in the presence of palladised charcoal in a hydrogen atmosphere with the production of a dimethylamino group (the reduction time is 3—12 h at 20°C). The free carboxyl group is esterified with diazomethane [260]. The general application of this procedure is limited, however, and the N,N-dimethylaminomethyl esters produced are very volatile so that mere evaporation of the ethereal solution of diazomethane at room temperature results in losses and low yields of the derivatives of Ala, Gly, Val and Leu. 

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