Intermediates diazo ketones

More definitive evidence for the formation of an oxirene intermediate or transition state was presented recently by Cormier 80TL2021), in an extension of his earlier work on diazo ketones 77TL2231). This approach was based on the realization that, in principle, the oxirene (87) could be generated from the diazo ketones (88) or (89) via the oxocarbenes 90 or 91) or from the alkyne (92 Scheme 91). If the carbenes (90) (from 88) and (91) (from 89) equilibrate through the oxirene (87), and if (87) is also the initial product of epoxidation of (92), then essentially the same mixture of products (hexenones and ketene-derived products) should be formed on decomposition of the diazo ketones and on oxidation of the alkyne this was the case. 

There are several reactions that are conceptually related to carbene reactions but do not involve carbene, or even carbenoid, intermediates. Usually, these are reactions in which the generation of a carbene is circumvented by a concerted rearrangement process. Important examples of this type are the thermal and photochemical reactions of a-diazo ketones. When a-diazo ketones are decomposed thermally or photochemically, they usually rearrange to ketenes, in a reaction known as the Wolff rearrangement.232... 

The use of copper as a catalyst in carbenoid transfer has its roots in the Amdt-Eistert reaction, Eq. 1 (3). Although the original 1935 paper describes the Wolff rearrangement of a-diazo ketones to homologous carboxylic acids using silver, the authors mention that copper may be substituted in this reaction. In 1952, Yates (4) demonstrated that copper bronze induces insertion of diazo compounds into the X-H bond of alcohols, amines, and phenols without rearrangement, Eq. 2. Yates proposal of a distinct metal carbenoid intermediate formed the basis of the currently accepted mechanistic construct for the cyclopropanation reaction using diazo compounds. 

A simple synthesis of a-amino ketones and esters 231 (R1 = EtO or Ph R2 = H or CO2EE R3 = Me or CH2C02Et R4 = PhCH2 or CH2C02Et) proceeds from diazo ketones and esters, respectively, tertiary amines and copper powder. The intermediate... 

The diazo ketones that are synthesized as intermediates are not only useful for the preparation of p-amino acids but may serve as versatile starting materials in different reactions, e.g. preparation of 3-azetidinones or 2-aminocyclopentanones. ... 

A regio- and stereospecific synthesis of modhephene has also been achieved beginning with the Weiss-Cook reaction As illustrated in Scheme XCVII, cyclo-pentai -l,2-dione can be readily crait l into a-diazo ketone 8(M), copper-catalyz l decomposition of which delivers tricyclic ketone 801. Following the dimethylation of this intermediate, carbomethoxylation was accomplished to give 802 and provide... 

In an approach to the stereocontrolled creation of the acyclic side-chain of tetracyclic triterpenoids and other natural products, Trost and his colleagues have converted the acyclic starting compound (29) into the cyclopropanoid intermediate (31) via the diazo-ketone (30). The key step in the scheme is the cleavage of the cyclopropane with lithium dimethylcuprate to give (32). The stereochemistry at C-7 is determined by the configuration of the double bond in (29). The c.d. and u.v. spectra of a series of triterpenoid olefins have been measured. The Scott-Wrixon rules can be used to correlate the sign of the c.d. curves with molecular structure. A... 

While the detailed mechanism of these rhodium-catalyzed cyclizations is not known, a working hypothesis that accommodates all of the observations to date is as follows. The diazo ketone can be considered to be a stabilized ylide, 14. Association of the Lewis acidic LUMO of the rhodium(II) carboxylate with the locally electron-rich ylide yields 15. Loss of nitrogen would then give the highly electrophilic intermediate 16. In nondonating solvents, the richest source of electron density available to this reactive species is the remote C—H bond. Complexation with the electron density in this bond gives 17, which collapses to the cyclopentanone product. 

When the Wolff rearrangement is carried out photochemically, the mechanism is basically the same,162 but another pathway can intervene. Some of the ketocarbene originally formed can undergo a carbene-carbene rearrangement, through an oxirene intermediate.168 This was shown by l4C labeling experiments, where diazo ketones labeled in the carbonyl group... 

Cyclopropanation. Molybdenum carbonyl catalyses cyclopropanation of a,[l-unsuturaied esters and nitriles by diazo ketones and esters, even at 25°. Molybdenum carhenes may be intermediates, and indeed carbene dimers are obtained in the absence of excess substnne. 

Although C—H insertion reactions rarely occur in intermolecular reactions with diazoacetates, these are common side reactions with diazomalonates3132 (equation 10) and diazo ketones (with a-allyl vinyl ethers).33 Several mechanistic pathways are available to generate the products of an apparent direct C—H insertion reaction and these include dipolar intermediates, ir-allyl complexes and ring opening of cyclopropanes.1 Oxidative problems due to the presence of oxygen are common with copper catalysts, but these are rarely encountered with rhodium catalysts except in systems where the carbenoid is ineffectively captured.34... 

Treatment of the diazo ketone 927 with a rhodium(n)-catalyst furnishes the 6-substituted 2,4-dihydropyran-3-one 929 arising from a proton transfer (1,4-shift) within the carbonyl ylide intermediate 928 (Scheme 251) <2002AGE1524>. 

Substituted furans 30 can be obtained in moderate yields by irradiation, in DCM with a high-pressure Hg lamp, of pyridazine-1-oxides (28 R2 = H) opportunely substituted with a group able to stabilize a carbene intermediate. The mechanism involves the open-chain diazo-ketone 29, which undergoes a photoinduced loss of molecular nitrogen leading to a carbene, which is a precursor of the final furans 30 (Scheme 12.9) [26]. 

Thiiranes are assumed to be intermediates in the formation of l-oxa-6,6aA4-dithiapen-talenes from l,2-dithiole-3-thiones reacting either with diazo ketones or with a-halogeno ketones with subsequent desulfuration in basic medium (71AHC(13)161, pp. 177-179). 

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