Diazo carbonyl functionality

Exploration of the scope and limitations of the formation of both types of heterocyclic azomethine imines with an exocyclic terminal nitrogen atom and/or isomers with a ring larger by one nitrogen atom and with all azomethine imine atoms incorporated into the ring requires the extension of the carbon tether (C) between the diazene and the diazo carbonyl functionalities of the co-diazenyl a -diazo ketone 37 (01TH). 

The comparison between the cycloaddition behavior of simple diazoketones and of ethyl diazopyruvate 56 towards the same olefin underlines the crucial influence of the ethoxycarbonyl group attached to the carbonyl function. This becomes once again evident when COOEt is replaced by an acetal function, such as in l-diazo-3,3-di-methoxy-2-butanone 86 with enol ethers and acetates, cyclopropanes rather than dihydrofurans are now obtained 113). ... 

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). 

A number of functional groups, such as nitro, diazo, carbonyl, disulfide sulfoxide, alkene, and pentavalent arsenic, are susceptible to reduction, although in many cases it is difficult to tell whether the reaction proceeds enzymatically or nonenzymatically by the action of such biologic reducing agents as reduced flavins or reduced pyridine nucleotides. In some cases, such as the reduction of the double bound in cinnamic acid (C6H5CH=CHCOOH), the reaction has been attributed to the intestinal microflora. Examples of reduction reactions are shown in Figure 7.12. 

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. 

A number of functional groups, such as nitro, diazo, carbonyls, disulfides, sulfoxides, and alkenes, are susceptible to reduction. In many cases it is difficult to determine whether these reactions proceed nonenzymatically by the action of biological reducing agents such as NADPFI, NADH, and FAD or through the mediation of functional enzyme systems. As noted above, the molybdenum hydroxylases can carry out, in vitro, a number of reduction reactions, including nitro, azo, A-oxidc, and sulfoxide reduction. Although the in vivo consequences of this are not yet clear, much of the distribution of reductases described below may be, in whole or in part, the distribution of molybdenum hydroxylases. 

While most of the initial studies have involved the transition metal-catalyzed decomposition of a-carbonyl diazo compounds and have been reviewed [3-51], it appears appropriate to highlight again some milestones of these transformations, since polycyclic structures could be nicely assembled from acyclic precursors in a single step. Two main reactivities of metalo carbenoids derived from a-carbonyl diazo precursors, namely addition to a C - C insaturation (olefin or alkyne) and formation of a ylid (carbonyl or onium), have been the source of fruitful cascades. Both of these are illustrated in Scheme 27 [52]. The two diazo ketone functions present in the same substrate 57 and under the action of the same catalyst react in two distinct ways. The initially formed carbenoid adds to a pending olefin to form a bi-cyclop. 1.0] intermediate 58 that subsequently cyclizes to produce a carbonyl ylide 59, that is further trapped intramolecularly in a [3 + 2] cycloaddition. The overall process gives birth to a highly complex pentacyclic structure 60. 

Calvo-Losada, S., Sordo, T. L., Lopez-Herrera, F. J., Quirante, J. J. The influence of protecting the hydroxyl group of P-oxy-a-diazo carbonyl compounds in the competition between Wolff rearrangement and [1,2]-hydrogen shift. Density functional theory study and topological analysis of the charge density. Theoretical Chemistry Accounts 2000,103,423-430. 

The application of the Forster reaction to the synthesis of a-diazo ketones is particularly important for derivatives of indanone and steroidal ketones with a methylene group in the a-position to the carbonyl function. The reaction allows functionalization of the a-methylene group. Examples include the synthesis of 2-diazo-3,3-diphenyl-indan-l-one (2-42 Cava et al., 1958) and 16-diazo-3)ff-hydro-xy-androst-5-en-17-one (2-43, Muller et al., 1962 Wheeler and Meinwald, 1988). 

As a diazo chemist, one is surprised that no dediazoniation is involved. Cleavage of the NN bond in part A of (9-27) is, however, well documented for hydrazone groups in the a-position to a carbonyl function (Cardinali et al., 1973). It is likely that part A consists, therefore, of three two-electron transfers, forming first the hydrazone, then the imine, and finally the amine 9.53. 

The tandem cycUzation-cycloaddition reactions of an a-diazo ketone with di-carbonyl functionalities placed on a flexible framework were performed to afford multiple dioxa-bridged polycycHc system 142 [128]. Interestingly, this reaction furnished the stereochemically favorable cycloadduct with dia-stereoselectivity and chemoselectivity (Scheme 44). 

Enantioenriched aziridines are important building blocks for the synthesis of functionalized chiral amines such as amino acid derivatives and hgands. In 2(X)8, Hashimoto et al. reported an axially chiral dicarboxyUc acid (66a)-catalyzed asymmetric aziridination of IV-Boc intines 64 with diazoacetantides 65, which resulted in trans-selective aziridine products 67 with up to 99% ee (Scheme 2.19) [30a]. The use of diazoacetantide 65 instead of diazoacetate as nucleophiles could lower the acidity of the a-proton of diazo carbonyls, thus leading to the formation of aziridine other than Mannich-type products. With this success, the same group recently established the asymmetric construction of... 

Carbonyl oxides (formed by the reaction of diazo compounds with singlet oxygen) may also be used to oxidize sulphoxides74. The corresponding sulphone is formed in reasonable yields and the reaction may be carried out in the presence of the sulphide functionality. The reaction proceeds as shown in equation (21) and involves initial nucleophilic attack by the carbonyl oxide on the sulphoxide sulphur atom followed by the facile departure of the carbonyl compound yielding the required sulphone. 

Types of compounds are arranged according to the following system hydrocarbons and basic heterocycles hydroxy compounds and their ethers mercapto compounds, sulfides, disulfides, sulfoxides and sulfones, sulfenic, sulfinic and sulfonic acids and their derivatives amines, hydroxylamines, hydrazines, hydrazo and azo compounds carbonyl compounds and their functional derivatives carboxylic acids and their functional derivatives and organometallics. In each chapter, halogen, nitroso, nitro, diazo and azido compounds follow the parent compounds as their substitution derivatives. More detail is indicated in the table of contents. In polyfunctional derivatives reduction of a particular function is mentioned in the place of the highest functionality. Reduction of acrylic acid, for example, is described in the chapter on acids rather than functionalized ethylene, and reduction of ethyl acetoacetate is discussed in the chapter on esters rather than in the chapter on ketones. 

Padwa et al. (44) studied the diazo-decomposition of 119 and found that the cyclic ylide 120 could be trapped by a variety of heterodipolarophiles such as ethyl cyanoacetate (Mander s reagent) to provide aminal 121 or with benzaldehyde to generate the bicyclic acetal 122. In both cases, only a single isomer was formed, with the regiochemistry easily predicted from frontier orbital considerations. Nair et al. (45) were able to employ the highly functionalized o-quinone 125 for the trapping of carbonyl ylide 124 to provide the highly complex cycloadduct 126 in 76% yield. 

---