Diazo-transfer reactions reagents

The diazo transfer reaction with sulfonyl azides has been extensively used for the preparation of diazo compounds with two electron-withdrawing groups (equation 1 ).28 Toluenesulfonyl azide (13a)29 is the standard reagent used, but due to problems of safety and ease of product separation, several alternative reagents have been developed recently. n-DodecylbenzenesuIfonyl azide (13b)30 is very effective for the preparation of crystalline diazo compounds, while p-acetamidobenzenesulfonyl azide (13c)31 or naph-thalenesulfonyl azide (13d)30 are particularly useful with fairly nonpolar compounds. Other useful reagents are methanesulfonyl azide (13e)32 and p-carboxybenzenesulfonyl azide (13f).33... 

The most widely used application of sulfonyl azides is in the azidation of enolates and other stabilized carbanions. The main challenge here is the avoidance of the diazo transfer reaction, which leads to diazo compounds and thus makes a diastereoselective animation impossible. Addition of the enolates to the sulfonyl azide proceeds rapidly at low temperatures (—78° or lower) to give the mesomeric ion 42 (Eq. 30).318 Reagents 41, the counter ion M+, the solvent, and the quenching reagent all influence the subsequent partition between azide and diazo compound. For enolates of esters (39) and N-acyloxazolidinoncs (40) the preferred reagent is trisyl azide (41a) 4-nitrobenzenesulfonyl azide (41c) promotes diazo transfer, and tosyl azide (41b) usually leads to mixtures of the two types of products. For ester enolates 39, either lithium or potassium as the... 

The mixture of eneaminoketones 121 is converted to the corresponding a-diazoketones 122 by alkylation with Bredereck s reagent followed by treatment with p-toluenesulfonyl azide. 7 The adenosine derivative (123) is treated with trifluoromethylsulfonyl azide to provide diazoketone 124 via deamination diazo transfer reaction in 72% yield.48... 

In diazo transfer reactions both N-atoms, i. e., the entire diazo group, are introduced into a suitable substrate from a diazo donor (2-46). In most cases this transfer reagent is a sulfonyl azide (Y=N2 = Ar-S02N=N2 or R-S02-N=N2), from which the N(yff)- and N(y)-atoms will form the diazo group in the product. There are, however, also cases in which the diazo group of an aromatic diazonium ion or of a diazoalkene is transferred. Such examples are of minor importance. 

The diazo transfer reactions, discussed in the synthesis Sections 2.6-2.8 clearly indicate that arylsulfonyl azides and other compounds with the azido group act as electrophilic reagents, that add to nucleophiles, e.g., to C-anions of so-called active methylene compounds. This result is qualitatively easy to comprehend, since the N()8) and N(y)-atoms of the azides are electronically similar to the diazonio group, as shown in the mesomeric structures 4.20b-4.20c. 

The two principal and most general synthetic routes to a-diazocarbonyl conpounds are (1) acylation of diazoalkanes and (2) diazo-transfer reactions to carbonyl conpounds with sulfonyl azide reagents. Caution Diazo conpounds and azide reagents are presumed to be toxic and potentially explosive, and appropriate safety measures should be deployed when handling these conpounds. 

Quinone diazides can also be obtained by the diazo group transfer reaction of 4-tosyl azide. For example, 9-diazo-10-anthrone (2.55) is formed from anthrone (2.54) if the reaction is carried out in an ethanol-piperidine mixture. On the other hand, if ethanol is replaced by pyridine, dimerization with loss of molecular nitrogen takes place and the azine 2.56 is isolated (Scheme 2-32 Regitz, 1964 Cauquis et al., 1965). In the preceding discussion tosyl azide was shown to be an electrophilic reagent. It therefore seems likely that it is not the anthrone 2.54 but its conjugate base which reacts with tosyl azide. 

Carbethoxy-4-diazo-l-phenylpyrazol-5-one (22a) (Scheme 88) was synthesized in 76% yield under mild conditions by direct introduction of the diazo group with the azidium salt 293 in sulfuric acid at room temperature [78H(10)199]. The easy introduction of the diazo group probably occurred because the a position of the ester was activated. On the contrary, tosyl azide failed to give the diazo derivative under the same conditions. Diazo transfer with this reagent only takes place under alkaline conditions, but in these reaction conditions, the diazo compound couples with the starting material. 

Trimethylsilyldiazomethane, as a stable and safe substitute for hazardous diazomethane, is useful both as a reagent for introducing a Cj-unit and as a C-N-N synthon for the preparation of azoles. Many methods are described in the literature for the preparation of trimethylsilyldiazomethane, including the trimethylsilylation of diazomethane (7-74S), the alkaline decomposition of N-nitroso-N-(trimethylsilylmethyl)amides (25-61%) and the diazo group transfer reaction of trimethylsilylmethyllithium with p-toluenesulfonyl azide (38%). The present modified diazo group transfer method appears to be the most practical, high-yield, and large scale procedure for the preparation of... 

The importance of a-diazo ketones as synthetic intermediates has led to the development of a number of general methods for their preparation.5 Particularly popular approaches include the acylation of diazo alkanes and the base-catalyzed "diazo group transfer" reaction of sulfonyl azides with 8-dicarbonyl compounds.6-7 While direct diazo transfer to ketone enolates is usually not a feasible process,8-9 diazo transfer to simple ketones can be achieved in two steps by employing an indirect deformylative diazo transfer strategy in which the ketone is first formylated under Claisen condensation conditions, and then treated with a sulfonyl azide reagent such as p-toluenesulfonyl azide.6a,6c,9,i0,11... 

Trifluoromethanesulfonyl azide, prepared in situ from trifluoromethanesulfonyl chloride and sodium azide in dimethylformamide, is reported to azidate phospho-noacetic esters and p-dicarbonyl compounds in the presence of triethylamine,309 whereas the same, but preformed, reagent gives the diazo compounds with a-nitro328 and a-cyano329 carbonyl compounds in the presence of pyridine. The reason for this dichotomy is not clear but because the former reaction was carried out under typical diazo transfer conditions the products may have been misidentified.330... 

The third procedure for the synthesis of phosphorylated diazoalkyl compounds is that of diazotization of the correspondingly substituted amino compounds, As a result of the ready availability of dimethyl and diethyl (aminomethyl)phosphonates, these form the most convenient starting materials for conversion into the dialkyl (diazomethyl)phospho-nate by the use of NaN02-acid . Latterly, the customary reagent combination has been that of propyl nitrite in acetic acid, and successful conversions have been described for 16 (Z = COOR CONHR and CN ). In the case of the last substrates, the diazo transfer procedure is said to be unsuitable, because of extensive side reactions which lead to phosphorylated 1,2,3-triazoles. Most reports have been concerned with the preparation of 1 -diazoalkyl compounds, and the syntheses of compounds in which the diazo group is sited elsewhere on the carbon skeleton are very rare ... 

There are several aspects of electron transfer reactions to and from diazo compounds First, the processes in an electrochemical cell, in particular those taking place at the surfaces of the cathode and the anode second, the structure of the intermediates and final products obtained in electrochemical processes third, reactions of diazo compounds carried out with inorganic and organic reduction or oxidation reagents. 

In a different approach, microwave-mediated oxazole synthesis utilizing ji-ketoesters bound to a novel polymeric resin has been described [57]. The desired polymer support was prepared by transesterification reactions between tert-butyl j5-ketoesters and hydroxybutyl functionalized Janda/el resin, and subsequent standard diazo transfer. The resulting a-diazo j5-ketoesters have been used for synthesis of an array of oxazoles (Scheme 16.34). Because of the thermal sensitivity of the Burgess reagent used, the temperature was kept rather low, but irradiation for 15 min at 100 °C furnished satisfactory results [57]. Cleavage from the solid support was achieved by diversity-introducing amidation this led to the corresponding oxazole amides in reasonable yields. 

---