Azides, Staudinger reaction

A similar microwave-assisted cyclization in the presence of ammonium acetate of an a-ketoamide, obtained by acylation of an a-aminoketone, was recently described for the synthesis of the antifungal agent Nortopsedin D [46]. The problem of the instabiUty of the a-amino ketones was successfully resolved by in situ acylation of the amine derived from Staudinger reaction of the azide 50 with a phosphine (Scheme 16). This ketoamide was... 

Recently, the same procedure has been used by Williams and coworkers in their approach to the natural product (-)-stemonine (7-18) [10], an alkaloid which exhibits broad biological activity [11]. Conversion of the formyl azide 7-16 in a Staudinger reaction with ethyldiphenylphosphine first generated a phosphineimide which was used for the subsequent aza-Wittig process (Scheme 7.7). The furnished seven-... 

Hydroxymethyl phosphines are susceptible to oxidation to form the phosphine oxide derivative. Therefore, avoid excess oxygen, oxidizing agents, or azide compounds, which react with phosphines in the Staudinger reaction (Chapter 17, Section 5). In addition, metallic surfaces can be modified via the phosphine group to result in hydroxymethyl group substitutions. 

Early in the last century, the Nobel Prize winning chemist Hermann Staudinger discovered a reaction between phosphines and azides, which became known as the Staudinger reaction (Staudinger and Meyer, 1919). Triphenylphosphine reacts with azides to form an intermediate iminophosphorane with the release of nitrogen gas. This intermediate quickly breaks down in aqueous environments to yield triphenylphosphine oxide and a primary amine (Figure 17.17). 

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.

This reaction has since been used successfully to synthesize amines in countless numbers of organic compounds and still remains one of the most common organic reactions performed today. Often azides are thought of as hidden amines, because the azide is relatively inert to other reactants until it is revealed through the Staudinger reaction. 

A variety of phosphate analogs have been synthesized and evaluated as glycosyl donors. Glycosyl phosphoramidimidates 73 are readily available from glycosyl phosphoramidites via a Staudinger reaction with phenyl azide (Scheme 6.14). Bearing... 

Tab. 5.2 Comparative Staudinger reactions using 19 and polystyrene-PPhs with the listed azides.

The so-called Staudinger reaction is limited only by the availability of the organic azides and their distinct tendency to decompose explosively. 

Wilson and Pasternak reported the first asymmetric Staudinger reaction (Scheme 4) where the chiral phosphane (7) reacts with the racemic azide (8) to afford diastereomeric iminophosphoranes in different quantities, giving after hydrolysis an amine in slight enatiomeric excess. Separation of the racemate seems to be kinetically controlled, but needs optimization (90MI1). 

Alternatively organic azides can easily be transformed into primary amines via a Staudinger reaction and subsequent hydrogenolysis (19HCA635 21HCA861 81T437 910PP1). 

Methyl 6-amino-6-deoxy-a-D-glucopyranoside derivatives 2c were synthesized in our laboratory by a somewhat different procedure [31]. 6-0-Sulfonyl or 6-bromo-6-deoxy derivatives of methyl a-o-glucopyranoside were substituted at C-6 by sodium azide. The 6-azido-6-deoxy intermediate was then treated by acyl chlorides in the presence of triphenylphosphine (Staudinger reaction) to afford amido derivatives which were finally de-O-acetylated to give 2c. The same reaction pathway allowed the preparation of 6-alkylamido-6-deoxy-D-glucopy-ranose derivatives, starting from o-glucose [31]. 

Staudinger reaction),615 H2 and a catalyst, Mg or Ca in MeOH,616 N2H4-Pd,617 and tin complexes prepared from SnCl2 or Sn(SR)2.6l i This reaction, combined with RX — RN3 (0-61). is an important way of converting alkyl halides RX to primary amines RNH, in some cases the two procedures have been combined into one laboratory step.61 Sulfonyl azides RS02N, have been reduced to sulfonamides RSO NH2 by irradiation in isopropyl alcohol620 and with NaH.621... 

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>. 

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. 

Esters of N-phosphoryl phosphazenes are usually formed by the Staudinger reaction which requires the handling of the extremely toxic phosphoric acid ester azides (eq. 1). For developing new synthetic... 

Cyclization of the furanose derivative 340 was mediated by the action of sodium hydride to afford 341 (R = Ts) in 90% yield. The amine 340 had been obtained from the azide 342 and it was later found that thermolysis of this 1,3-azido alcohol under Staudinger reaction conditions (triphenylphosphine in f-xylene) gave the azetidine 341 (R = H) directly in 99% yield <2003TL5267>. 

Reaction of otfi-unsaturated acetals with silyl nucleophiles. This trityl salt is an efficient catalyst for reaction of the dimethyl acetal (2) of cinnamaldehyde with successive silyl nucleophiles to form y,5-unsaturated p-azido ketones. The azide group can be reduced to an amino group by the Staudinger reaction.1... 

Isocyanates have provided one carbon atom in transformations of the general type (296) - (290). Thus, azide (343) reacts with triphenylphosphine in a Staudinger reaction giving phosphorane (344) which is then treated with isocyanates (RNCO R = benzyl or aryl) giving naphthyridines (346) (50-59% yield) via the carbodiimide (345). The cyclization (345)->(346) occurred in toluene at 160°C (92T4601). Azide (347) undergoes a similar sequence of reactions yielding a 1 1 mixture of isomeric naphthyridines (348) and (349) (44—47% yield). 

---