Carbenes, from diazocarbonyls

Table 4.4. Intramolecular 1,4-C-H insertions of electrophilic carbene complexes generated from diazocarbonyl compounds.

Table 4.19. C-O Bond insertion reactions of acceptor-substituted carbene eomplexes generated from diazocarbonyl compounds.

By 1960, there was recognition that copper salts could cause the loss of dinitrogen from diazocarbonyl compounds with addition of the resulting carbene intermediate to a carbon-carbon double bond to form a cyclopropane product. That this reaction, first reported by G. Stork in 1961 (Eq. 6), could occur in an intramolecular fashion and thus avoid the formation of isomers, ushered in the first significant synthetic... 

For a review of the intramolecular insertions of carbenes or carbenoids generated from diazocarbonyl compounds, sec Burke Grieco Org. React. 1979,26, 361-475. 

We showed you the formation of a carbene from diazomethane to illustrate how this reaction was different from the (ionic) methylation of carboxylic acids. But this is not a very practical way of generating carbenes, not least because of the explosive nature of diazoalkanes. However, diazocarbonyl compounds are a different matter. 

The most important methods for the synthesis of thiane and thiepane derivatives involve sulfonium ylide formation. The most graceful and effective of these is the intramolecular cyclization of carbenes derived from diazocarbonyl and diazodicarbonyl compounds. In some cases, the latter provide stable sulfonium ylides. Thus, ylides 455 ( = 1 R = Et, Ph) were produced on heating diazo compounds 456 ( = 1 R = Et, Ph) in 62 and... 

The ability of chiral bis(camphorquinone-a-dioximato)cobalt(Il) complexes (Section 1.2.1.2.4.2.6.3.1.) to catalyze carbene transfer from diazocarbonyl compounds (diazoacetic esters, 2-diazo-l-phenylethan-l-one) to terminal alkenes conjugated with vinyl, aryl, carbonyl, and cyano groups, has already been mentioned. The ee-values are 75-88 /o at best, often lower. The highest values are again obtained with bulky diazoacetic esters. The significance of these catalysts, however, is their ability to promote cyclopropanation of electron-deficient alkenes, such as acrylates and acrylonitriles, in contrast to the rhodium and copper catalysts discussed above. 

Miller, D. J., Moody, C. J., Synthetic Applications of the O H Insertion Reactions of Carbenes and Carbenoids Derived from Diazocarbonyl and Related Diazocompounds, Tetrahedron 1995, 51, 10811 10843. 

Carbenes from a-Diazocarbonyl Compounds The Wolff Rearrangement and the Arndt-Eistert Reaction... 

Cyclopentanones and other five-membered ring-containing compounds can be prepared readily by intramolecular C—H insertion of carbenes derived from diazocarbonyl compounds and rhodium(n) acetate. Thus, treatment of the diazoketone 99 with rhodium(II) acetate gave the C—H insertion product 100, used in a synthesis of the toxin muscarine (4.78). 

Miller DJ, Moody CJ (1995) Synthetic applications of the O-H insertion reactions of carbenes and carbenoids derived from diazocarbonyl and related diazo compounds. Tetrahedron 51 10811-10843... 

Based on a detailed investigation, it was concluded that the exceptional ability of the molybdenum compounds to promote cyclopropanation of electron-poor alkenes is not caused by intermediate nucleophilic metal carbenes, as one might assume at first glance. Rather, they seem to interfere with the reaction sequence of the uncatalyzed formation of 2-pyrazolines (Scheme 18) by preventing the 1-pyrazoline - 2-pyrazoline tautomerization from occurring. Thereby, the 1-pyrazoline has the opportunity to decompose purely thermally to cyclopropanes and formal vinylic C—H insertion products. This assumption is supported by the following facts a) Neither Mo(CO)6 nor Mo2(OAc)4 influence the rate of [3 + 2] cycloaddition of the diazocarbonyl compound to the alkene. b) Decomposition of ethyl diazoacetate is only weakly accelerated by the molybdenum compounds, c) The latter do not affect the decomposition rate of and product distribution from independently synthesized, representative 1-pyrazolines, and 2-pyrazolines are not at all decomposed in their presence at the given reaction temperature. 

Interaction of an electrophilic carbene or carbenoid with R—S—R compounds often results in the formation of sulfonium ylides. If the carbene substituents are suited to effectively stabilize a negative charge, these ylides are likely to be isolable otherwiese, their intermediary occurence may become evident from products of further transformation. Ando 152 b) has given an informative review on sulfonium ylide chemistry, including their formation by photochemical or copper-catalyzed decomposition of diazocarbonyl compounds. More recent examples, including the generation and reactions of ylides obtained by metal-catalyzed decomposition of diazo compounds in the presence of thiophenes (Sect. 4.2), allyl sulfides and allyl dithioketals (Sect. 2.3.4) have already been presented. 

A density functional study has been made of the competition between Wolff rearrangement and [1,2]-H shift in /S-oxy-a-diazocarbonyl compounds. Silver-catalysed decomposition of a-diazoketones (88 n = 0), derived from A-tosyl a-amino acids in methanol, gave rise to mixtures of products of Wolff rearrangement (89) and direct insertion of the carbene into the NH bond (90). The -amino acid derived species (88 n = 1) gave rise to products of Wolff rearrangement. 

Ethers, sulfides, amines, carbonyl compounds, and imines are among the frequently encountered Lewis bases in the ylide formation from such metal carbene complex. The metal carbene in the ylide formation can be divided into stable Fisher carbene complex and unstable reactive metal carbene intermediates. The reaction of the former is thus stoichiometric and the latter is usually a transition metal complex-catalyzed reaction of a-diazocarbonyl compounds. The decomposition of a-diazocarbonyl compounds with catalytic transition metal complex has been the most widely used approach to generate reactive metal carbenes. For compressive reviews, see Refs 1,1a. 

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-... 

The intermediacy of metal-carbene complexes in these reactions is suggested by the observation that carbene-transfer reactions exhibit a chemo- and stereoselectivity similar to those which start from the corresponding diazocarbonyl compounds. 

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