2-/- , Staudinger reaction

Phosphazo compounds (e.g. iminophosphoranes) from the reaction of tertiary phosphine (e.g. Ph3P) with organic azides. 

Kovdcs, J. Pinter, I. Kajtar-Peredy, M. Sows, L. Tetrahedron 1997,53,15041. 

R = alkyl, aryl, heteroaryl, RC(0), RSO2, RP(0), R2P, RsSi, RsSn, RsGe R = H, alkyl, aryl, heteroaryl X = alkyl, aryl, O-alkyl, O-aryl, NH2, NR2, Cl, F, NCO, (also the combination of these ligands) Y = Cl, Br Z = O, S solvent THF, Et20 

The total synthesis of the antiviral marine natural product (-)-hennoxazole A was accomplished by F. Yokokawa and co-workers. The mild reduction of a secondary alkyl azide at C9 was carried out using triphenylphosphine in a THF/water mixture at slightly elevated temperature. The corresponding primary amine was obtained in good yield and was subsequently acylated and converted to one of the oxazole rings of the natural product. 

BU3P (1.7 equiv), toluene, r.t., 2h then heat to reflux, 20h 82% 

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. 

The research team of S.R. Rajski demonstrated that o-carboalkoxy triarylphosphines react with aryl azides to afford Staudinger ligation products bearing O-alkyl imidate linkages. In comparison, the reaction of alkyl azides with o-carbalkoxy triarylphosphines usually gives rise to amide linkages. The importance of this technique lies in its ability to couple abiotic reagents under biocompatible conditions. 

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The 3-[2-(acylamino)phenyl]-2-azidoprop-2-enoates 1 undergo a Staudinger reaction on treatment with triphenylphosphane at 20 C to give the stable imino-/.5-phosphanes 2 in nearly quantitative yields. The latter cyclize to 3/7-1,3-benzodiazepines 3 (40-50%) when heated in refluxing xylene for 15 hours. No further details were reported.19... 

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... 

The use of chiral auxilliaries in the Staudinger reaction has been explored extensively. Chiral imines derived from (15)-(-t-)-camphor 10-sulfonic acid <96TA2733>,... 

The Staudinger reaction [92], a [2 + 2]-cycloaddition of a ketene and a nucleophilic imine, usually proceeds by an initial imine attack on the ketene thus forming a zwitterionic enolate which subsequently cyclizes. This reaction is an expedient route to p-lactams, the core of numerous antibiotics (e.g., penicillins) and other biologically active molecules [93]. In contrast, for Lewis-base catalyzed asymmetric reactions, nonnucleophilic imines are required (to suppress a noncatalyzed background reaction), bearing, for example, an N-Ts [94] or -Boc-substituent [95]. 

Zhang YR, He L, Wu X, Shao PL, Ye S (2008) Chiral N-heterocyclic carbene catalyzed Staudinger reaction of ketenes with imines highly enantioselective synthesis of W-Boc P-lactams. Org Lett 10 277-280... 

Lee EC, Hodous BL, Bergin E, Shih C, Fu GC (2005) Catalytic asymmetric Staudinger reactions to form P-lactams an unanticipated dependence of diastereoselectivity on the choice of the nitrogen substituent. J Am Chem Soc 127 11586-11587... 

Staudinger reaction conditions obviate the need for interim protection... 

The spirophosphorane (115) has been found to react with triphenylphosphine by a conventional Staudinger reaction to produce (116) with the novel X5 P-N-X4P grouping 2L ray data are available for the latter51. ... 

Staudinger reaction lead to the preparation of unprotected sugar... 

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. 

Figure 17.24 The traceless Staudinger reaction can be used to form larger peptides from smaller peptides, if one contains an azido group at the N-terminal and the other one contains a phosphine ester at its C-terminal. The reaction gives a native peptide (amide) bond with loss of the phosphine group.

Saxon, E., and Bertozzi, C.R. (2000) Cell surface engineering by a modified Staudinger reaction. Science 287, 2007-2010. 

The two-step Staudinger reaction has been investigated in depth and 13-azadienes 56 have been isolated in some cases. The evidence suggests that the enol ether group is crucial in the stabilization of the diene and also plays an important role in promoting the conrotatory ring closure process . 

The Staudinger reaction of -substituted o-azidobenzamides 83 with triphenylphosphine yields phosphazides 84 which react with isocyanates to give, unexpectedly, the corresponding 1,23-benzotriazinone derivatives 85 <00T4079>. 

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