Azides and Diazo-compounds

Azides have been prepared in excellent yields by the reaction of 

Vicinal azidohydrins have been prepared by treating epoxides with Et Al/NH in toluene.This mild and selective transformation of 

Azide-substituted a-diazo-amides were prepared from glycyl 481 

2-azido-2,3-dideoxy-3-fluoro-sugars, precursors of fluoro amino 

Polymeric quaternary ammonium azides permit clean nucleophilic 

As discussed above reductions of azides can provide access to both amines and amino-alcohols. The latter is particularly important in the carbohydrate area where classical methods of azide formation by displacements of halides and sulphonates plus additions to epoxides can all be readily achieved. 

It has been shown that allylic, benzylic, and tertiary alkyl halides may be substituted in good yields by using sodium azide and 

Epoxide openings performed with azidotrimethylsilane and di-ethylaluminium fluoride in dichloromethane afforded 3-azido-1,2-diols with good stereo- and regio-selectivities (C2 N2 C2-N2 83 17 

Thus optimum conditions were substrate azide Lewis acid = 1 2 4. 

In combination with methanol, azidotrimethylsilane was used to generate hydrazoic acid situ, and this in turn was responsible for ring opening of chiral epoxides derived from the tartaric 

Primary amines result from the hydrogenation of azides at room temperature and 3-4 atmospheres over platinum oxide or palladium catalysts. 2 jhe addition of acid is sometimes beneficial. Raney nickel is a less efficient catalyst for this reaction. 

Azides are hydrogenated with retention of configuration (Eqn. 19.31). This, in conjunction with the nucleophilic character of the azide ion, provides an efficient method for the stereospecific introduction of a primary amine group into a molecule. 

Aryl diazomethanes and ethyl diazoacetate lose nitrogen completely when hydrogenated over palladium in neutral medium at room temperature and atmospheric pressure. Aryl diazoketones, however, under the same conditions, give the a-amino ketones which condense directly to the dihydropyrazines. The addition of acetic acid to the solvent for this later reaction permits the isolation of the amino ketone (Eqn. 19.32). With dilute hydrochlorie acid in the reaction mixture, complete loss of the nitrogen was observed. The hydrogenation of alkyl diazoketones in neutral or acetic acid solution results in hydrazone formation (Eqn. 19.33).  

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Smith and Knowles (1973) made several 3-H-3-aryldiazirines and suggested that they had several advantages as photoaffinity labeling reagents over the aryl azides and diazo compounds that were then current. These diazirines did not become popular, however, because they are inconvenient to prepare. The situation today is unchanged. 

The stability of the reagent to the assay conditions should also be ascertained. The instability of azides and diazo compounds towards thiols was mentioned earlier, and it would be prudent to ensure that all new reagents whether they contain familiar photoactivatable groups or not are stable to the prevailing chemical and enzymatic conditions. In an attempt to label the cAMP receptor of D. discoideum, Wallace and Frazier (1979b) found that 8-N rcAMP was converted to NrAMP by the phosphodiesterase of a crude membrane preparation. The NrAMP specifically labeled actin and not the cAMP receptor. 

Three atom ring-expansion of cyclopropenyl azides and diazo-compounds provides a useful route to triazines and pyridazines respectively 278). 

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... 

Arynes are novel reaction intermediates that react with dienes or 1,3-dipoles to give the corresponding cycloadducts. Recently, many researchers have reported the reaction of benzyne prepared from 2-(trimethylsilyl)phenyl triflate or benzenedia-zonium carboxylate with imines, aminobenzoate, 2-aminobenzophenones, azides, and diazo compounds, which provides various N-containing cycloadducts, such as acridines, acridones, triazoles, and indazoles. Formally, the reaction proceeds in a [2-1-2], [3-1-2], or [4-1-2] manner. Benzyne is an extremely reactive species because of the presence of a strained triple bond and undergoes polar and pericycHc reactions. The lifetime of benzyne in the gas phase has been estimated to around 20 ns (2 X 10" s) by mass spectroscopic techniques. Some spectroscopic properties of benzyne have been determined by Orville Chapman using matrix isolation techniques (Scheme 7.20). 

In support of this mechanism is the fact that stable cobaltacyclopentadienes 11.23, with an additional PPhs ligand can be prepared (Scheme 11.12). These cobaltacycles undergo further reactions with alkynes, alkenes, azides and diazo compounds to give a variety of cyclic products. Cyclobutadiene complexes 11.26, cyclopentadienone complexes 11.27 and arenes 11.28 can also be formed (Scheme 11.13). ... 

Since the terminal nitrogen atom of electronegatively substituted azides and diazo compounds displays distinctly electrophilic properties, attack at this site by peraminoethylenes comes as no surprise. Both Wanzlick and ReimUnger have discovered that 5 reacts with diazofluorene to give the azine (61). 

Lewis Acid-Catalyzed Site-Selective Cycloadditions of 2,6-Diazasemibullva-lenes with Isocyanides, Azides and Diazo Compounds Novel Reaction Patterns Leading to Diaza- and Triaza-Brexadiene Derivatives. 

Herein, the author reports Lewis acid-catalyzed diverse cycloaddition reactions of NSBVs 6-1 with a wide variety of isocyanides, azides, and diazo compounds. These reactions afforded 5,8-diaza- and 2,5,9-triaza-brexadiene derivatives as highly fused A -containing polycyclic frameworks, which are structurally and chemically interesting cage-shaped compounds, but not readily accessible by other means. Unique and unprecedented rearrangement-cycloaddition patterns are revealed. These reaction patterns are not only different from our previously reported reaction with DMAD or RNCO, but most notably, very different from the reactions... 

Fig. 6.5 Cycloaddition patterns of 2,6-diazasemibullvalenes with isocyanides, azides, and diazo compounds catalyzed by different lewis acids...

Zhang S, Zhang WX, Xi Z (2013) Lewis acid-catalyzed site-selective cycloadditions of 2,6-diazasemibullvalenes with isocyanides, azides and diazo compounds novel reaction patterns leading to diaza- and triaza-brexadiene derivatives. Angew Chem Int Ed 52 3485-3489... 

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