Diazo functionality

The diazo function in compound 4 can be regarded as a latent carbene. Transition metal catalyzed decomposition of a diazo keto ester, such as 4, could conceivably lead to the formation of an electron-deficient carbene (see intermediate 3) which could then insert into the proximal N-H bond. If successful, this attractive transition metal induced ring closure would accomplish the formation of the targeted carbapenem bicyclic nucleus. Support for this idea came from a model study12 in which the Merck group found that rhodi-um(n) acetate is particularly well suited as a catalyst for the carbe-noid-mediated cyclization of a diazo azetidinone closely related to 4. Indeed, when a solution of intermediate 4 in either benzene or toluene is heated to 80 °C in the presence of a catalytic amount of rhodium(n) acetate (substrate catalyst, ca. 1000 1), the processes... 

In the context of 12, the diazo keto function and the thiolactam are in proximity. This circumstance would seem to favor any process leading to the union of these two groupings. It is conceivable that decomposition of the diazo function in 12 with rhodium(n) acetate would furnish a transitory electron-deficient carbene which would be rapidly intercepted by the proximal thiolactam sulfur atom (see 20, Scheme 4). After spontaneous ring contraction of the... 

Diazo function Bridging group X Reaction conditions Yield 10.48 + 10.49 % Ratio 10.48 10.49... 

The structure elucidation of the kinamycins was a formidable challenge, and the information presented below draws from the work of several research groups over a period of more than 20 years. As will be shown, the originally proposed structure of the kinamycins contained a cyanamide rather than a diazo function. Subsequent synthetic and biosynthetic studies led to replacement of the cyanamide with a diazo function. The structural elucidation was challenging, in part, because of the high degree of unsaturation of the kinamycins, which limits the utility of H and 2D NMR analysis. In addition, because these structures were unprecedented, there were no clear benchmarks for comparison at the time. The pathway from isolation to determination of the correct structure is described below. 

Gould and coworkers have extensively studied the biosyntheses of the kinamycins, and this work was recently reviewed [5a]. Feeding studies established that the carbo-cyclic skeletons of the kinamycins are constructed from 10 equivalents of 5-acetyl coenzyme A, and the pathway shown in Scheme 3.4 was proposed. The pathway begins with formation of the natural product dehydrorabelomycin (29). A novel ring contraction then occurs to form the cyclopentadienone 30. Feeding studies with /V-15-ammonium sulfate established that the diazo functional group is then installed... 

The methoxymethyl ether protecting groups of 33 were then cleaved using triphenylphosphine and carbon tetrabromide. The resulting hydroquinone function was oxidized by palladium on carbon under an atmosphere of air to afford the quinone 52 (70 %). A two-step procedure was implemented to install the diazo function. First, the ketone function of 52 was condensed with N,N -bis( tert-butyldimethylsilyl)hydrazine in the presence of scandium triflate, which formed the Af-tert-butyldimethylsilyl hydrazone 53. The hydrazone (53) was then oxidized using difluoroiodobenzene to afford kinamycin C (3) in 35 % yield. 

The isolation of diazobenzo[fr ]fluorenes as stable antitumor natural products raises several questions about their mode of action. The inability to cleave DNA by diazotization of 9-aminofluorene may imply that if the diazo functionality is involved in the mode of interaction of kinamycins with DNA, its conversion to diazonium and the ensuing reduction may seem to be of negligible importance. An additional possibility, which will be discussed later, is that 9-diazofluorene may not be the ideal model for these natural products. In exploring DNA cleavage as a possible route to the kinamycins role as a stable antitumor agent, which may supplement their speculative and as yet unconfirmed role as alkylating molecules [67], this early model seemed to suggest that the well-established activation of diazonium may not be relevant. 

This degenerate rearrangement has not been observed with 5-dia-zomethyl-l,4-diphenyl-l,2,3-triazole. The diazo function decomposes and the carbene formed reacts, when benzene is used as solvent, into a cyclo-heptatriene. The requirement to have the ester function present at C-4 apparently has to do with stabilization of the diazo function. 

The key reaction, based on a method for removing glutamate residues in peptides, involves the conversion of the sole primary amine in the molecule to a diazo function. The most expeditious method consists of reacting (18-1) with nitrosyl chloride. The resulting diazo function in the product (18-2) can be displaced formally by oxygen from the enol form of the amide at the 7 position to form the iminolactone (18-3) the reaction may involve a spontaneous loss of nitrogen followed by capture of the resulting carbocation. Hydrolysis of the imine function in the product the leads to one of the key intermediates in this series, 7-ACA (18-4) [22]. 

To date, bis(diazomethyl)silanes represent the only precursors to silylene-dicarbenes. It should be noted, however, that the extrusion of N2 from the two diazo functions can occur more or less simultaneously or successively. In the latter case, a diazocarbene is formed in the first place, which is supposed to undergo a fast carbene reaction before the generation of a carbene from the second diazo function occurs. This should be kept in mind for all transformations which are explained mechanistically with the participation of silylene-dicarbenes. There are even examples where only one of the two diazo groups enters carbene chemistry at all (see equations 35 and 36 below). 

A diazosilene is probably also involved in the photochemical or copper-catalyzed decomposition of bis(diazoacetate) 156 in benzene (equation 36). In both cases, dia-zoketene 157 was the only identified product72. Its formation was explained by the silylcarbene-to-acylsilene-to-silylketene sequence outlined in Scheme 5. Efforts to achieve the N2 extrusion from the remaining diazo function by thermolysis in boiling toluene or by prolonged photolysis resulted only in unspecific decomposition. 

As another example, photolysis in inert solvents of compound 275, where four SiMe2 groups bridged the two diazo functions, led to the bis-silene 276, which reacted by either head-to-head or head-to-tail pathways resulting in the formation of the bicyclic compounds 277 and 278, respectively. Alternatively, [2 -f 3] cycloaddition gave the intermediate 279 which led to the formation of the bicycloadduct 280 (Scheme 49). 

When H-acid is used as a double coupling component, as in 13, in which reactive groups are present in both diazo functions, the resulting dye color ranges from blue to black. 

Rearrangement of jS-thio-a-diazo carbonyl compounds (44) occurred upon decomposition of the diazo function by metals, especially Rh(II).43 1,2-Thio migration adducts (45) were obtained with moderate to high diastereoselectivities. The outcome of the decomposition of (46) by Rh(II) was shown to be highly dependent on the nature of the X substituent.44 When X = OH, (47) has been exclusively observed, whereas (48) was the only product isolated when X = NHC(0)CC13. 

In contrast with 3-diazo-37/-indoles, 2-diazo-277-indoles show C NMR spectra similar to those of the corresponding diazonium salts and do not show an appreciable upfield shift at the carbon bound to the diazo function, that is, the C-2 carbon, which resonates at S 110-115 <2001HCA2212>. These data support a structure largely zwitterionic in character in which the negative charge is mainly located on the indole nitrogen. 

After their discovery by E. O. Fischer and A. Maasbdl in 1964 [1], a large number of carbene complexes with various transition metals such as Cr, Mo, W, Mn, and Fe were prepared [2]. Their synthetic applications in organometallic and organic chemistry increased rapidly, especially with respect to annelation reactions (Ddtz reaction). Among all known Fischer carbene complexes there is no example featuring a diazo functionality. In this contribution we describe the synthesis of a new class of Fischer-type carbene complexes with a diazomethylsilyl substituent in a-position to the carbene carbon-atom. 

Copolymerization with diazo-functionalized monomers in emulsion has been employed for the preparation of highly cross-linked poly(methylmethacrylate) lattices with diazo groups covalently fixed to the core (Figure 22). Thermal decomposition of the diazo groups allowed selective grafting of a shell [254-256]. 

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