Diazoketones reaction with alkenes

Whereas metal-catalyzed decomposition of simple diazoketones in the presence of ketene acetals yields dihydrofurans 121,124,134), cyclopropanes usually result from reaction with enol ethers, enol acetates and silyl enol ethers, just as with unactivated alkenes 13). l-Acyl-2-alkoxycyclopropanes were thus obtained by copper-catalyzed reactions between diazoacetone and enol ethers 79 105,135), enol acetates 79,135 and... 

Diazomethane is a valuable and useful agent in organic synthesis that can be employed as a Ci building block in many single-step chemical reactions, for example, the methylation of alcohols or phenols, esteriflcations of carbonic adds, cyclopropanation reactions with alkenes, the synthesis of heterocycles, and the synthesis of a-diazoketones from acid chlorides or anhydrides. In general, the reactions proceed with release of nitrogen. Usually, diazomethane is freshly prepared from N-methyl-nitroso compounds and aqueous KOH solution and can be stored as a cooled solution for a couple of days. However, its low boiling point... 

Some other electrophiles that convert alkenes to cyclopropanes are not free carbenes but have metals coordinated with their electrophihc site. These are called carbenoids and include the Simmons-Smith reaction and the copper-, rhodium-, or palladium-catalyzed decomposition of diazoketones and esters (Section 7.3). That the metal atom is present in the electrophile is shown by the variation of the stereoselectivity of the reaction with changes in the other ligands on metal. 

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). 

An efficient way to attach carboxylic acid derivatives directly to Cgg was found with the reaction of the corresponding diazoketones 158-162 with Cgg in toluene or methybiaphthalene at elevated temperatures [133]. The [6,6] closed cycloaddition products are formed in moderate yields although a significant amount of a side-product was produced. This side-product was found to be a dihydrofuran fused CgQ-adduct The direct reaction product of the malic acid derivative 162 without elimination of AcO H could not be isolated instead the trans-alkene 163 was formed and isolated in 18% yield. 

Silyl-substituted diazoketones 29 cycloadd with aryl isocyanates to form 1,2,3-triazoles 194 (252) (Scheme 8.44). This reaction, which resembles the formation of 5-hydroxy-l,2,3-triazoles 190 in Scheme 8.43, has no analogy with other diazocarbonyl compounds. The beneficial effect of the silyl group in 29 can be seen from the fact that related diazomethyl-ketones do not react with phenyl isocyanate at 70 °C (252). Although the exact mechanistic details are unknown, one can speculate that the 2-siloxy-1-diazo-1-alkene isomer 30 [rather than 29 (see Section 8.1)] is involved in the cycloaddition step. With acyl isocyanates, diazoketones 29 cycloadd to give 5-acylamino-l,2,3-thiadiazoles 195 by addition across the C=S bond (252), in analogy with the behavior of diazomethyl-ketones and diazoacetates (5). 

The diverse chemistry of carbenes is beyond the scope of this account, but a few typical reactions are shown here to illustrate the usefulness of the photochemical generation of these reactive species. A carbene can insert into a C—H bond, and this finds application in the reaction of an a-diazoamide to produce a P-lactam (5.29). Carbenes derived from o-diazoketones can rearrange to ketenes, and thus a route is opened up to ring-contraction for making more highly strained systems <5.301. Carbenes also react with alkenes, often by cycloaddition to yield cyclopropanes in a process that can be very efficient (5.31) and highly stereoselective (5.321. 

Rhodium(II) acetate catalyzes C—H insertion, olefin addition, heteroatom-H insertion, and ylide formation of a-diazocarbonyls via a rhodium carbenoid species (144—147). Intramolecular cyclopentane formation via C—H insertion occurs with retention of stereochemistry (143). Chiral rhodium (TT) carboxamides catalyze enantioselective cyclopropanation and intramolecular C—N insertions of CC-diazoketones (148). Other reactions catalyzed by rhodium complexes include double-bond migration (140), hydrogenation of aromatic aldehydes and ketones to hydrocarbons (150), homologation of esters (151), carbonylation of formaldehyde (152) and amines (140), reductive carbonylation of dimethyl ether or methyl acetate to 1,1-diacetoxy ethane (153), decarbonylation of aldehydes (140), water gas shift reaction (69,154), C—C skeletal rearrangements (132,140), oxidation of olefins to ketones (155) and aldehydes (156), and oxidation of substituted anthracenes to anthraquinones (157). Rhodium-catalyzed hydrosilation of olefins, alkynes, carbonyls, alcohols, and imines is facile and may also be accomplished enantioselectively (140). Rhodium complexes are moderately active alkene and alkyne polymerization catalysts (140). In some cases polymer-supported versions of homogeneous rhodium catalysts have improved activity, compared to their homogenous counterparts. This is the case for the conversion of alkenes direcdy to alcohols under oxo conditions by rhodium—amine polymer catalysts... 

Certain diazoketones, for example diazopyruvate, alkyl 2-diazo-3-oxobutyrate or 3-diazo-2,4-pentanedione, react with vinyl ethers under metal catalysis to give dihydrofurans rather than cyclopropanes l Most work on this type of transformation has been that of Wenkert and Alonsoand their respective groups. A representative example is shown in equation 107. Finally, carbenoid dimerization is also a competitive reaction in metal catalysed intermolecular cyclopropanation. However, control of the chemoselectiv-ity to favour the cyclopropanation is possible. In general, the dimeric product can be avoided by using excess of alkene or by very slow addition of the diazo compound to a mixture of alkene and catalyst... 

Polymer-supported benzenesulfonyl azides have been developed as a safe diazotransfer reagent. ° These compounds, including CH2N2 and other diazoalkanes, react with metals or metal salts (copper, paUadium, and rhodium are most commonly used) to give the carbene complexes that add CRR to double bonds. Diazoketones and diazoesters with alkenes to give the cyclopropane derivative, usually with a transition-metal catalyst, such as a copper complex. The ruthenium catalyst reaction of diazoesters with an alkyne give a cyclopropene. An X-ray structure of an osmium catalyst intermediate has been determined. Electron-rich alkenes react faster than simple alkenes. ... 

Rhodium acetate is the usual catalyst for cyclopropane formation from the reaction of a-diazoketones with alkenes though the Lewis acid (f -C5H5)Fe (CO)2(THF)BF4r has also been used". ... 

Intramolecular reactions of carbenes with alkenes have been exploited in synthesis. The sesquiterpene cycloeudesmol was prepared using, as a key step, the intramolecular cyclopropanation of the diazoketone 122 (4.97). The cyclopropana-tion reaction occurs stereoselectively to give the tricyclic product 123, which was subsequently converted into the natural product. A synthesis of sesquicarene was achieved using the copper(I)-catalysed decomposition of the diazo compound 125, itself prepared by oxidation of the hydrazone 124 (4.98). 

Rh (CO)i6 is a highly active catalyst in the reaction of ethyl diazoacetate with alkenes to give cyclopropyl esters. Yields obtained are better than those obtained using palladium and copper catalysts. Methyl ester derivatives of tricyclo[4.2.0.0 ]octane have been prepared by a photochemical Wolff rearrangement of a related diazoketone in methanol. ... 

The 4(4 -n.butyl phenylazo)phenylbutyric acid described earlier is easily converted to an acid chloride and thence to a wide variety of activated or activatable species, including acylazide, amine (by acyl azide rearrangement), diazoketone (with diazomethane), iodide (by Huns-diecker reaction) and alkene (by treatment with Wilkinson s catalyst). Alkenes are easily converted to silanes, so that this offers a direct route to a derivative of the type used by Sagiv in the work mentioned earlier. 

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