Azides, Staudinger reduction

Azides may be converted to amines by hydrogenation, but another possibility is the Staudinger Reaction, which is a very mild azide reduction. As there are a variety of methods for preparing azides readily, the Staudinger Reaction makes it possible to use "N3 as an" NH2 synthon. 

Azides are converted into amines by the Staudinger reaction. It is a very mild azide reduction with triphenylphosphine. ... 

STAAB Reagent 358 STAUOINGER Azide reduction 359 STAUDINGER PFENNINQER Thsrane dnxide synthesis 360... 

Treatment of enecarbamate 344 with sodium azide and ceric ammonium nitrate (CAN) in acetone furnished azidocarbazole 345. The low yield in this oxidative cychzation reaction is due to formation of the diastereomer consisting of stereochemical inversion at the azide-substituted carbon. At this point, azide reduction employing the Staudinger conditions of triphenyl-phosphine in a mixture of water and THF led to an amine, which was subjected to trichloroacetyl chloride in a solution of dichloromethane and triethylamine to yield amide 346 (Scheme 49). 

Ashfeld and coworkers proposed that the initial phosphinylation of oxime 2 and subsequent Staudinger-like reduction of the tosyl azide forms iminophosphorane 171 (Scheme 5.42k The formation of the phosphoryl bond upon rearrangement is a likely driving force behind the regioselective migration of the trans-oxime substituent (R in 171) to afford the nitriliumion 5. The corresponding anionic phosphoramide is released and then adds to the nitrilium ion amidine 17. A subsequent 1,3-phosphoryl shift leads to the final amidine product 173. 

Ene-nitrile oxidoisoquinolinium betaine 131 was readily prepared from vinyl triflate aldehyde 79 (Scheme 1.14). Palladium-catalyzed cyanation of vinyl triflate 79 with Zn(CN)2 in DMF at 60 °C produced ene-nitrile aldehyde 129 in 85 % yield [54]. Using the previously developed Staudinger-aza-Wittig reduction sequence, aldehyde 129 was coupled with cyclic ketal azide 121 to afford a 79 % yield of amine 130. The cyclic ketal amine 130 was then treated with 9 1 mixture of CH2CI2/TFA to provide ene-nitrile oxidoisoquinolinium betaine 131 in 93 % yield. 

Figure 17.17 The Staudinger reaction involves the reduction of an azide to a primary amine with loss of N2 and the concomitant oxidation of a phosphine derivative to a phosphine oxide.

There now are available a number of alkyl azide compounds that may be used in click chemistry reactions and the Staudinger ligation processes. It is not recommended, however, to use aryl azide compounds, as these are light sensitive and photoreactive as well as highly susceptible to reduction in the presence of thiols. Unfortunately, at the time of this writing there are fewer choices in aryl phosphine compounds to participate in this reaction, as commercial sources of labeling reagents are limited. 

Ring opening of oxiranes using azide is followed by Staudinger reduction of the intermediate azido alcohol to give aziridines. 

The selective reduction of the azide of pyrrole 150 via Staudinger reaction followed by hydrolysis led to the formation of 151, which underwent reductive cyclization with zinc under basic conditions to afford pyrrole[l,2,5]-benzotriazepine 29 (Scheme 33) <1996T10751>. 

Exposure of sulfolane 261 to sodium azide and mesylation regioselectively afforded mesylate 262, which was transformed into aziridine 263 by a three-step sequence involving azide to amine Staudinger reduction, acetylation, and ring closure. The trans 1,2-diamino derivative 264 was quickly obtained from 263 by azide opening of the aziridine ring, followed by reduction. 

By far the most common method of formation of IMPs is the Staudinger reaction.1 This is the reduction of an organic azide with triphenylphosphine (Scheme 4). It has been proven that attack of the phosphorus is at the terminal nitrogen of... 

In the first step a Staudinger reduction of the azide to the amine takes place, wherein triphenylphosphine reacts with the azide and forms a phosphazide, which then loses N2 and forms the iminophosphorane. Aqueous workup then generates the amine with phosphine oxide as a side product. The amine formed then undergoes macrolactonization to 63 with loss of acetone. 

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. 

Staudinger reduction Reduction of azides with triphenylphosphine. 428... 

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