Methylene from diazoalkanes

In contrast to the wealth of chemistry reported for catalyzed reactions of diazocarbonyl compounds, there are fewer applications of diazomethane as a carbenoid precursor. Catalytic decomposition of diazomethane, CH2N2, has been reported as a general method for the methylenation of chemical compounds [12]. The efficacy of rhodium catalysts for mediating carbene transfer from diazoalkanes is poor. The preparative use of diazomethane in the synthesis of cyclopropane derivatives from olefins is mostly associated with the employment of palladium cat-... 

Due to their tendency to undergo side reactions and the lack of stereospecificity, free methylene or alkylcarbenes, as generated from diazoalkanes by photolysis or thermal nitrogen extrusion, are of minor synthetic importance for [2 4- 1] cycloadditions. However, transition metal catalysis, most commonly with copper or palladium compounds, offers a convenient solution to this problem (Vol. E19b. p 278)s. Probably the most active catalyst is copper(I) trifluoromcthanesulfonate9. The simple diastereoselectivity of these reactions is often negligible, as demonstrated by the copper(I) chloride or palladium(II) bis(benzonitrilo)dichloride promoted cyclopropanation of phenylethene with diazoethane10. 

Herzberg and collaborators provided the first experimental evidence that a meta-stable, bent singlet was initially produced from diazoalkane and decayed to a ground-state triplet. - The hquid-phase chemistry of methylene, for example, is simple in comparison with its gas-phase chemistry. However, hot molecules produced by extremely exothermic reactions of methylene play a minor role in the gas phase. Carbenes have been used on countless occasions to make three-membered rings via [1+2]-cycloaddition. 

Numerous methods to prepare individual classes of aliphatic diazo compounds have been extensively developed. The major strategies for their synthesis involve the alkaline cleavage of N-alkyl-N-nitroso-ureas, -carboxamides and -sulfonamides, dehydrogenation of hydrazones, as well as diazo group transfer from sulfonyl and related azides to active methylene compounds, and electrophilic diazoalkane substitution reactions. These synthetic methods have been comprehensively reviewed (15,16). Useful information on the preparation of selected diazo compounds can be found elsewhere (6,17). 

In the light-induced reactions with diazoalkanes, methylene, the photolytic fragment from diazomethane, may be interposed between the halogen atom in the organic halide and the carbon atom to which it is attached,289 290 or may add to the double bonds in the aromatic ring.58 69... 

Finally, mention should be made of the synthesis of the trinuclear ju.-methylene anion of composition [ /z-C(H)C02C2H5 Fe3(CO)i0(/x-H) ]. Once again, the diazoalkane has been used to add the carbene to the corresponding metalcarbonyl framework of the [HFe3(CO)nJ precursor. The structure of the product was inferred from spectroscopic data (323). 

Cycloaddition of diazoalkanes to 6-6 bonds was among the first reactions tested on the carbon cages41 and affords isolable fullerene-fused pyrazolines as primary adducts. Photochemically induced extrusion of N2 from the latter yields 6-6-closed methanofullerenes having the functionalized bond embedded in a cyclopropane substructure, whereas the thermal process affords 6-5 open homofullerenes in which a methylene group is bridging the open junction between a six- and a five-membered ring.15-17... 

The formation of desaurins from ketones, carbon disulfide, and base 1275,1281,1282,1285-1290 believed to involve nucleophilic attack on a thioketene by the dianion of a 1,1-dimercaptoalkene, as shown for the synthesis of 572. Related syntheses involve the use of thiophosgene instead of carbon disulfide and the use of diazoalkanes or phosphonium and sulfonium ylides instead of a ketone and base. Treatment of perfluoroiso-butylene with fluoride ion and elemental sulfur in a dipolar, aprotic solvent ° °° or with sources of anionic sulfur (potassium sulfide, sodium hydrosulfide,potassium thiocyanate,sodium thiosulfate, dithiocarbamate salts, dithiophosphate salts ) give the dimer (573) of bis(trifIuoromethyl)-thioketene. Similarly, other 2,4-bis(methylene)-l,4-dithietanes are obtained by treating 2,2-dichlorovinyl ketones with anionic sulfur re-... 

Although the addition of carbene to a double bond to make a cyclopropane is well known, it is not particularly useful synthetically because of the tendency for extensive side reactions and lack of selectivity for thermally or photochemically generated carbenes. Similar processes involving carbenoids (species that are not free carbenes) are much more useful from the preparative standpoint [91,92]. For example, metal catalyzed decomposition of diazoalkanes usually results in addition to double bonds without the interference of side reactions such as C-H insertions. Consider the possible retrosynthetic approaches to a 1,2-disubstituted cyclopropane shown in Figure 6.8. Disconnection a entails the addition of a methylene across a double bond, a conversion that is often stereospecific e.g., the Simmons-Smith reaction [93]). Disconnections b and c are more problematic, since the issue of cis/trans product isomers (simple diastereoselection) arises. 

An example for the introduction of a diazoalkane ligand into a cluster complex built from three osmium atoms with nine CO molecules and one diphenylacetylene (10.77) was described by Shapley s group (Clauss et al., 1981). The reaction yields almost equal amounts of a thermally stable //-diazomethane adduct (10.78) and a //-methylene complex (10.79 10-35). This dediazoniation product can also be obtained from the//-diazomethane adduct 10.78 by irradiation. An X-ray structure of a related Os complex was published more recently by Day et al. (1992). 

The metallocarbene intermediates are most often formed from thermal, photolytic, or metal-catalyzed deconposition of diazocarbonyl compounds, with concomitant loss of dinitrogen. Under transition metal catalysis, the initially formed species is a metallocarbene rather than a free carbene, and this is usually desirable due to the moderated reactivity (and, hence, fewer undesired side reactions) of the metal-complexed carbene. The two most common methods for introduction of the diazo group are acylation of diazoalkanes with suitably activated carboxylic acid derivatives and diazo transfer reactions in the case of more acidic active methylene substrates fScheme 16.12T... 

Examples of selective heteronuclear NOEs used in structure determination and signal assignment are shown in Fig. 2.36 (2, 339, 383). The correct assignments of the carbonyl carbon resonances of citraconic anhydride, (30), were made from the observed NOEs upon irradiation of the vinyl proton and the vinylic methyl group (383). In pentalenolactone G, (31), thought to be a biosynthetic precursor of pentalenolactone, the location of the gem-dimethyl at the C-2 and the methylene carbon at C-3, rather than the gem-dimethyl at C-3 and the methylene at C-2, was shown by enhancement of the ketonic carbonyl upon irradiation of both the methyl and methylene protons (339). A final example shows the use of heteronuclear NOEs to establish the structure of a quinone-diazoalkane adduct (32) (2). Enhancements of the carbon signals at d = 90.0, 90.5, and 195.0, upon irradiation of the one-proton singlet at 2.37, H-3a, supported the structure of the adduct as 32. 

While the alkylation of compound 207 with diazoalkanes clearly indicates its enol character, some other reactions reveal that it can also behave as a typical (3-ketoester. For example, reduction with sodium borohydride in aqueous methanol yielded the saturated alcohol (208) which after chromatography was isolated as a crystalline substance in 30% yield. Acetylation with acetic anhydride in pyridine gave 3-acetox-ycepham (209) from which the acetic acid was eliminated upon treatment with triethylamine in methylene chloride, affording the 3-H cephalosporin (210). 

Obviously, the first example of poly(substituted methylene) synthesis (PSMS) is polymerization of diazoalkanes and aryldiazomethanes, which was extensively studied in 1950-1970 [9-11] and whose importance as an alternative method for polyolefin synthesis was well recognized. In that period, in spite of the high explosiveness of the diazo compounds, many researchers were engaged in the polymerization and some unique and important characteristics for the process were revealed. Although some reviews of the polymerization were published [9-11], it is worthwhile to mention briefly some of the representative results, which are closely related to the contents of the later sections of this review. In addition, the unique character of surface-catalyzed polymerization of diazomethane has been utilized for surface modification recently, which is also described in this section. The efficient synthesis of nanometer-scale polymethylene thin films from diazomethane is quite remarkable, compared to the difficulty of polyethylene thin film formation because of the low solubility of the polymer. 

Adamantanethione was converted into a thiiran by addition of a methylene group, derived from methylenetriphenylphosphorane, across the carbon-sulphur double bond. The action of Grignard and other organometallic reagents on thiones gives thiirans together with other products, and thiirans also are obtained by treatment of 3-piperidino-2-phenylindene-l-thione with several diazoalkanes. ... 

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