Ketocarbene

Decomposition of the diazoimide (551) by heating in the presence of copper acetylaceton-ate also generated a ketocarbene (552). This undergoes an intramolecular condensation to give the anhydro-4-hydroxy-3-methyl-4-p-nitrophenyl-2-phenyloxazolium hydroxide (553), which cannot be prepared by more classical means (75CL499). 

In this review an attempt is made to discuss all the important interactions of highly reactive divalent carbon derivatives (carbenes, methylenes) and heterocyclic compounds and the accompanying molecular rearrangements. The most widely studied reactions have been those of dihalocarbenes, particularly dichlorocarbene, and the a-ketocarbenes obtained by photolytic or copper-catalyzed decomposition of diazo compounds such as diazoacetic ester or diazoacetone. The reactions of diazomethane with heterocyclic compounds have already been reviewed in this series. ... 

With a few recent exceptions the reactions in this group have been with the a-ketocarbenes, CH COOMe, CH COOEt, and CH-COCHs, derived from the corresponding diazo compounds. Sorm and coworkers have reported the ring-opening of furan and methylfurans upon reaction with diazoacetone decomposed by copper, via attack at... 

The diazo ketone 3, when treated with silver oxide as catalyst, decomposes into ketocarbene 5 and dinitrogen Na. This decomposition reaction can also be achieved by heating or by irradiation with uv-light. The ketocarbene undergoes a Wolff rearrangement to give a ketene 6 ... 

An a-diazo ketone 1 can decompose to give a ketocarbene, which further reacts by migration of a group R to yield a ketene 2. Reaction of ketene 2 with water results in formation of a carboxylic acid 3. The Woljf re arrangement is one step of the Arndt-Eistert reaction. Decomposition of diazo ketone 1 can be accomplished thermally, photochemically or catalytically as catalyst amorphous silver oxide is commonly used ... 

The ketocarbene 4 that is generated by loss of Na from the a-diazo ketone, and that has an electron-sextet, rearranges to the more stable ketene 2 by a nucleophilic 1,2-shift of substituent R. The ketene thus formed corresponds to the isocyanate product of the related Curtius reaction. The ketene can further react with nucleophilic agents, that add to the C=0-double bond. For example by reaction with water a carboxylic acid 3 is formed, while from reaction with an alcohol R -OH an ester 5 is obtained directly. The reaction with ammonia or an amine R -NHa leads to formation of a carboxylic amide 6 or 7 ... 

The intermediacy of a ketocarbene species 4 is generally accepted for the thermal or photochemical Wolff rearrangement oxirenes 8 that are in equilibrium with ketocarbenes, have been identified as intermediates ... 

The photolysis of o-quinone diazides was carefully investigated by Stis in 1944, many years before the development of photoresists. Scheme 10-102 shows the photolysis sequence for the diazoquinone 10.75 formed in the diazotization of 2-amino-1-naphthol. The product of the photolytic step is a ketocarbene (10.76), which undergoes a Wolff rearrangement to a ketene (10.77). In the presence of water in-dene-3-carboxylic acid (10.78) is formed this compound is highly soluble in water and can be removed in the development step. The mechanism given in Scheme 10-102 was not postulated as such by Stis, because in 1944 ketocarbenes were unknown (for a mechanistic discussion of such Wolff rearrangements see review by Zollinger, 1995, Sec. 8.6, and Andraos et al., 1994). 

Tsuda and Oikawa (1989) investigated the photolysis of the 1,2-isomer of 10.89 (1,2-benzoquinone diazide) by means of MINDO/3 molecular orbital calculations with configurational interaction. These authors came to the conclusion that no ketocarbene of the type of 10.90 is formed, but that the rearrangement into the cyclopentadienyl ketene 10.94 is a concerted reaction in which the elimination of nitrogen and the rearrangement take place simultaneously. In the opinion of the present author the theoretical result for 1,2-quinone diazide is not necessarily in contradiction to the experimental investigations of Sander, Yankelevich et al., and Nakamura et al., as the reagents used were not exactly the same. 

Kalvar process 284 Ketenes 284ff., 288 Ketocarbenes 284ff., 287... 

When the Wolff rearrangement is carried out photochemically, the mechanism is basically the same, but another pathway can intervene. Some of the ketocarbene orieinallv formed can undergo a carbene-carbene rearrangement, through an oxi-... 

Oxazole formation can be envisaged as proceeding by three possible pathways 1,3-dipolar cycloaddition of a free ketocarbene to the nitiile (Path A), the formation and subsequent 1,5-cyclisation of a nitrile ylide (Path B) or the formation and subsequent rearrangement of a 2-acyl-2//-azirine (Path C) (Scheme 9). 

Although non-stereospecific [3 + 2] cycloaddition of ketocarbenes is well established and despite their classification as 2n-rather than 4-ti-components, hence not belonging to those 1,3-dipoles which are expected to cycloadd stereospecifically132),... 

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). 

Insertion of a ketocarbene moiety into a C—O bond of orthoesters is normally performed with catalysis by BF3 Et20. Copper(II) trifiouromethanesulfonate was found to be a similarly efficient catalyst also, at least in some cases, whereas Rh2(OAc)4 was much less suited to promote this transformation l60). Besides the C/O insertion product 343, the alcohol insertion product 344 and, in reactions with ethyl diazoacetate, the formal carbene dimers were obtained. In agreement with BF3 EtzO, Cu(OTf)2 did not bring about insertion into a C—O bond of trimethyl... 

Ketocarbenes generated from diazoketones give two main type of reactions. The first one is the conventional carbene reaction, i.e. intramolecular insertion into a C—H or C—C bond, as applied in the synthesis of a... 

The second reaction mode is rearrangement of the ketocarbene to a ketene. In the presence of a C—C double bond this species reacts further via an intramolecular photocycloaddition (cf. chapter 4.3.3), as shown in (2.23) 238). 

The photolysis of cyclic diazo ketones in hydroxylic solvents leads to ring contracted carboxylic acid derivatives via this ketocarbene -> ketene rearrangement. Examples of such reactions are given in (2.24)239) and (2.25) 240). In this last example a photoequilibrium between the diazo ketone and its valence isomer, a diazirine, has been observed, both products then eliminating nitrogen to afford the cyclobutane carboxylic acid. 

Our interest in ketocarbenes originated from the aim to matrix-isolate oxirene (76) (Scheme 1), the oxygen-containing hetero analog of cyclobutadiene (1)... 

In the list of diazoketones studied by us95 mostly derivatives were included which have in solution no or only a small tendency for a Wolff rearrangement. Nevertheless we found not a single diazoketone 71 which enabled us to identify a ketocarbene 72, only the corresponding ketenes 73 could be detected. The same observation was made when we studied in collaboration with Yannoni et al." the photochemically induced deazotation of l-diazo-2-propanone in an organic matrix at 77 K, using 13C CPMAS NMR spectroscopy as the analytical tool. 

The linear polymerization of Scheme 7.15 represents an unusual case of diazoacetophenone oxidation. For instance, on the action of copper oxide, diazoacetophenone gives ketocarbene, which is involved in typical carbene reactions such as dimerization, addition to olefins, and insertion in the 0-H bonds of alcohols. If the amine cation-radical is used as an oxidant instead of copper oxide, only the polymer is formed. The ketocarbene was not observed despite careful searches (Jones 1981). 

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