Azides, vinyl synthesis

Harvey and Ratts have discovered an interesting vinyl azide synthesis from allenic esters.40 Treatment of allenes (83a and b) with... 

The base-catalyzed condensation of a-azido esters and ketones with aromatic aldehydes has recently been developed as a new vinyl azide synthesis.42,43 The yields range from moderate to excellent in some cases. The thermal decomposition of ethyl a-azidocinnamate (87) in xylene gives only 2-ethoxycarbonylindole (88).44 The unstable 2-ethoxycarbonyl-3-phenyl-l-azirine could be detected if the thermolysis was carried out at a lower temperature. This fact indicates that the 1-azirine is probably an intermediate leading to the indole, although the intermediacy of the vinyl nitrene could not be established. This result is similar to that observed by Isomura et al. on the pyrolysis of terminal vinyl azides.27,28... 

The most obvious route to vinyl azide synthesis lies in the addition of hydrazoic acid to an alkyne. Unfortunately, this reaction has been found to be successful with only one group of compounds, the esters of acetylene dicarboxylic acid (equation 1). Acetylene mono-... 

A mechanism for this reaction involving nucleophilic attack of the ylide on the cyanide group and formation of the P=N linkage via a four-centred intermediate was formulated. The structure of this phosphazene was confirmed by its synthesis from the vinyl azide, Ph(N3)C=CHPh, and triphenylphosphine. Phosphoranes stabilized by electron-withdrawing... 

Synthesis of Acyclic Iodo Azides and Vinyl Azides... 

Smolinsky developed the first general synthesis of 1-azirines by the vapor phase pyrolysis of vinyl azides (41).20,21 In addition to 50-60%... 

The free radical addition of bromine azide has been complementary to iodine azide for the synthesis of some vinyl azides. Using bromine azide /5-azidostyrene (57) has been prepared from styrene (76) through bromoazide (77).37... 

The displacement of activated vinyl halides and sulfinates has also been used for the synthesis of some vinyl azides (82).24, 30,38,39... 

Related to the above method is the addition of hydrazoic acid to conjugated acetylenes (85) which has been applied to the synthesis of the vinyl azide (86).41... 

One of the best known reactions of 1-azirines is the acid/catalyzed hydrolysis to aminoketones. Since the Neber reaction also accomplishes this same synthetic end, this reaction may appear to have little practical value. This is not the situation because with the Neber reaction there is no control over the aminoketone that will be obtained from a given ketone. For example, when oxime (127) derived from benzyl methyl ketone (126) is subjected to the Neber reaction aminoketone 128 is obtained.59 The amino function is substituted for the most acidic a-hydrogen. The isomeric aminoketone (132) that could not be prepared by the Neber reaction can be formed by the hydrolysis of 1-azirine (131). The synthesis of this 1-azirine has been accomplished from allyl benzene (129) through vinyl azide (130) using iodine azide.22... 

D. Lloyd and H. McNab, Angew. Chem., Int. Ed. Engl. 15,459-468 (1976). Synthesis of heterocycles, from vinyl azides ... 

Replacement in vinylic derivatives is, however, facilitated by electron-withdrawing groups to the site of substitution and addition-elimination reactions of this type have been reviewed by Rappoport and by Patai and Rappoport Such reactions have been applied in the direct synthesis of vinyl azides. For example the synthesis in 81 % yield of the )5-azidovinyl ketone (25), of unspecified stereochemistry, from the chloro derivative and azide ion in dimethylformamide at 40° has been described by Maiorana . 

In the synthesis of the terminal vinyl azide (36) by reaction of 9-bromomethylenefluorene with azide ion in dimethylformamide the halogen atom is activated by the pan-activating hydrocarbon nucleus. Similar treatment of the dichloromethylene derivative (37) results in a more complex reaction. 9-Azido-9-fluorenecarbonitrile (38) is produced and Smolinsky and Pryde have rationalized the formation of this product by the sequence shown in equation (28). 

The synthesis of vinyl azides by regiospecific elimination of hydrogen iodide from vicinal iodoazides has been developed by Hassner and co-workers and constitutes the only noteworthy example of the directing effect of the azido group on elimination reactions. 

The development of newer methods for synthesis of vinyl azides enabled the preparation of series of azirines, including fused ones such as 138 . 

The same general method was applied to the synthesis of amino-ketones directly from vinyl azides (39) the presence of 0 5%... 

The absolute configuration of the structurally unique fungal metabolite mycosporins was determined in the laboratory of J.D. White by means of enantioselective total synthesis." In the endgame of the synthetic effort, the Staudinger reaction was used to elaborate the side chain. The cyclic vinyl azide was first converted to a stable vinyl iminophosphorane, which was subsequently reacted with benzyl glyoxylate to afford the corresponding Schiff base. Reduction of the imine was achieved with sodium cyanoborohydride. 

Moody, C.J., and Warrellow, G.J., Vinyl azides in heterocyclic synthesis. Part 10. Synthesis of the isoindolobenzazepine alkaloid lennoxamine, J. Chem. Soc., Perkin Trans. 1, 2929, 1990. 

A new synthesis of 2,5-di- and 2,4,5-trisbustituted oxazoles begins with -(acyloxy)vinyl azides... 

Nitrene insertion. A nitrene insertion reaction is central to many syntheses of pyridoacridine alkaloids and their analogues. For example, Labarca et al. [87JCS(P1)927] have reported a three-step synthesis of a pyridoacridine 169 starting from 2-methoxyacridine-9-carboxaldehyde 165 (Scheme 26). Cyclization of the vinyl azide 166 by thermolysis is believed to involve a nitrene insertion reaction, to give either 167 or 168. 

The dediazoniation of the vinyl azide proceeds via vinyl nitrene. A variant of this synthesis enables the preparation of 3-(dialkylamino)-2//-azirines starting from A,7V-disubstituted acid amides [15] ... 

Few examples of azirine synthesis via enaminones are found in the literature, as azirines tend to undergo further reactions to give more stable compounds. One important method is the vinyl azide-olefin cycloaddition where the azides can be considered as derivatives of enaminones. The chemistry of this unique reaction has been reviewed (75AGE775). A recent example is included in Scheme 17, in which intramolecular cycloadditions of vinyl azides 53 furnish azirines 54 (87CB2003). In a similar reaction, the aziridinoindoies 56 are synthesized from 55 by insertion of the azide-derived nitrene into the olefinic bond (89H2029). 

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