Ketones, from diazoketones

Alkylation.—Position-specific alkylation of ketones can be achieved by a number of new methods. Vinyloxyboranes, formed by reaction of trialkyl-boranes with diazoketones or by radical addition to methyl vinyl ketone, react with alkyl-lithium reagents to give the corresponding lithium enolates, which undergo facile, site-specific alkylation this allows the formation of aa-disubstituted ketones from diazoketones and a/3-disubstituted ketones from methyl vinyl ketone (Scheme 80). 

Diiron enneacarbonyl, 50, 2J Diketones, from diazoketones and organoboranes, 53/ 82 3-DIKETONES FROM METHYL ALKYL KETONES 3-n-BUTYL-2,4-PENTANEDIONE, 51, 90 2,6-Dimethoxybenzaldehyde, by reduction of 2,6-dime thoxy-benzonitrile with Raney nickel alloy in formic acid,... 

Doering et al." extended this application to the synthesis of tricyclic ketones from monocyclic diazoketones, using as catalyst copper powder, cupric sulfate, or cuprous iodide with apparently equal success. A sketchy advance report,12 claims the synthesis of 8,9-dehydroadamantane-2-one (5, m.p. 206.5-207.5°) via the acid chlorides (3) and (4) and the derived diazoketones. 

The photoelimination of nitrogen from diazoketones and the fate of the resulting species are still subjects of major interest. A successful photochemically induced Wolff rearrangement of an acyclic /Sy-unsaturated diazo-ketone in aqueous dioxan has been reported.60 In the photodecomposition of the diazo-ketone... 

Observations from both Nierenstein and Robinson have enabled the understanding of this reaction. It is also accepted that excess diazomethane at lower temperatures leads to diazoketones because hydrogen chloride liberated gets consumed by its preferential reaction with excess diazomethane to form methyl chloride 5. This explains why hydrogen chloride gas added through an external source to a solution of diazoketone can drive the Nierenstein to completion. Further evidence to support this theory was offered by McPhee and Klingsberg in the procedure for the synthesis of benzyl chloromethyl ketone from phenylacetyl chloride, by which the diazoketone is separately treated with hydrogen chloride at 0 °C and also by Bhatt et al. in their synthesis of a-chloromethyl-3,4,5-triacetoxy acetophenone in which diazoketone is the key intermediate. ... 

Cuprous oxidelirradiation Cyclic ketones from a-diazoketones... 

A key observation by Wenkert proved vital in the subsequent popularity of rhodium as a highly effective catalyst for the generation of carbenes from diazoketones and their engagement in C-H insertion reactions (Equation 27) [15, 16, 88], In this experiment, treatment of diazoketone 153 with Rh2(OAc)4 led to a stereoselective C-H insertion reaction to generate ketone 154 in 59% yield [88], Importantly, no cyclization was observed in the presence of CuSO,. 

During 1961-2 four independent groups almost simultaneously reported the first syntheses of D-norsteroids, based on the photolysis of 16-diazo-17-ketones. In a typical procedure. Cava and Moroz ° convert the 16-oximino-17-one (93) derived from estrone methyl ether (92) to the diazoketone (94)... 

The synthesis of cycloheptatrienyl ketones 233 from benzene and a-diazoketones 232 proceeds in essentially quantitative yield the products were not isolated but directly transformed into benzyl ketones 234 through the action of trifluoroacetic acid 229 ... 

The reaction, formally speaking a [3 + 2] cycloaddition between the aldehyde and a ketocarbene, resembles the dihydrofuran formation from 57 a or similar a-diazoketones and alkenes (see Sect. 2.3.1). For that reaction type, 2-diazo-l,3-dicarbonyl compounds and ethyl diazopyruvate 56 were found to be suited equally well. This similarity pertains also to the reactivity towards carbonyl functions 1,3-dioxole-4-carboxylates are also obtained by copper chelate catalyzed decomposition of 56 in the presence of aliphatic and aromatic aldehydes as well as enolizable ketones 276). No such products were reported for the catalyzed decomposition of ethyl diazoacetate in the presence of the same ketones 271,272). The reasons for the different reactivity of ethoxycarbonylcarbene and a-ketocarbenes (or the respective metal carbenes) have only been speculated upon so far 276). 

Intramolecular oxonium ylide formation is assumed to initialize the copper-catalyzed transformation of a, (3-epoxy diazomethyl ketones 341 to olefins 342 in the presence of an alcohol 333 . The reaction may be described as an intramolecular oxygen transfer from the epoxide ring to the carbenoid carbon atom, yielding a p,y-unsaturated a-ketoaldehyde which is then acetalized. A detailed reaction mechanism has been proposed. In some cases, the oxonium-ylide pathway gives rise to additional products when the reaction is catalyzed by copper powder. If, on the other hand, diazoketones of type 341 are heated in the presence of olefins (e.g. styrene, cyclohexene, cyclopen-tene, but not isopropenyl acetate or 2,3-dimethyl-2-butene) and palladium(II) acetate, intermolecular cyclopropanation rather than oxonium ylide derived chemistry takes place 334 ). 

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). 

Where the carbon-carbon double bond is a part of an aromatic system, in general, cyclopropanation of diazoketones results in the formation of unstable cyclopropane adducts. For example, Saba140 has shown that in the intramolecular cyclopropanation of diazoketone 57 the norcaradiene ketone 58 can be detected by low-temperature NMR and can be trapped in a Diels Alder reaction with 4-phenyl-l,2,4-triazoline-3,5-dione (equation 69). In addition, Wenkert and Liu have isolated the stable norcaradiene 60 from the rhodium catalysed decomposition of diazoketone 59 (equation 70)105. Cyclopropyl ketones derived from intramolecular cyclopropanation of hetereoaromatic diazoketones are also known and two representative examples are shown in equations 71 and 72106. Rhodium(II) compounds are the most suitable catalysts for the cyclopropanation of aromatic diazoketones. 

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