Reduction Staudinger

Phosphazo compounds (e.g., iminophosphoranes) from the reduction of organic azides using tertiary phosphine (e.g., PhsP). Hydrolysis then provides the corresponding amines. 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 260, Springer International Publishing Switzerland 2014 

Staudinger Reaction. In Name Reaction. for Functional Group Transformations, Li, J. J., Ed. Wiley Hoboken, NJ, 2007, pp 129-151. (Review). 

4-Dicaibonyl derivatives from aldehydes and a,p-unsaturated ketones and esters. The thiazolium catalyst serves as a safe surrogate for CN. Also known as the Michael-Stetter reaction. Cf. Benzoin condensation. 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 243, Springer-Verlag Berlin Heidelberg 2009 

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Scheme 7.6. Synthesis of (-)-vasicinone (7-15) by a domino Staudinger-reduction/aza-Wittig reaction.

Staudinger reduction/aza-Wittig/Ugi three component reaction... 

NaBH(OAc)3 Staudinger reduction followed by aza-Wittig reaction, then reduction... 

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

Reduction of amides is an important preparative method for the synthesis of primary amines. Reducing agents used for this purpose include lithium aluminum hydride, sodium borohydride, triphenyl-phosphine (Staudinger reduction), and thiols. In the present case it is important to consider the compatibility of the reduction system with the carboxylic and methanesulfonic acid functions. Platinum and palladium arc often used for catalytic reduction. 

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. 

Staudinger reduction/aza-Wittig/Ugi three component reaction 2 -trimethyls ilylethoxymethoxy single-electron transfer Shell Higher Olefin Process... 

A promising new chemoselective ligation procedure has also been developed that utilizes a-azidoacyl peptides that are acylated by peptide thioesters under the Staudinger reduction conditions using 2-phosphanylbenzenethiol for transesterification of the thioester, trapping of the azido component as the phosphazene followed by intramolecular O N acyl shift (Scheme 78).t 5336,84i]... 

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. 

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

Azides react with tertiary phosphines under mild conditions to form iminophosphoranes (1), which are versatile synthetic intermediates that have found a number of applications.1- 0 Upon treatment with water, an iminophosphorane will hydrolyze to form a primary amine and phosphine oxide in what is referred to as the Staudinger reaction or Staudinger reduction. 

One of the reasons that the Staudinger reduction is such a powerful synthetic tool is the fact that azides can be introduced into a molecule fairly easily.1-2 In fact, some of the improvements to the Staudinger reduction over the years have included many one-pot protocols converting alkyl bromides, alkyl chlorides, alcohols, and acetates to azides followed by the in situ reduction to the corresponding amines using the Staudinger reaction. 

Numerous examples of the use of the Staudinger reduction in the synthesis of complex biologically active compounds appear in the literature (see Section 2.5.5) and synthetically useful variations have been developed. 

Carbamates are one of the most widely used protecting groups for amines and the development of one-pot conversions of azides to carbamates such as Boc, Cbz, and allyl further expanded the scope of utility of the Staudinger reduction. Treatment of the Staudinger reaction iminophosphorane intermediate 26 with 1.05 equivalents of 2-t-(butoxycarbonyloximino)-2-phenylacetonitrile (Boc-on) led to Boc-protected amines 28 thru 32 in 87-100% overall yield.19 This process utilizes trimethylphosphine, which is more reactive than triphenylphosphine and provides an easier work-up because trimethylphosphine oxide is water soluble. It should be noted that the use of di-f-butyldicarbonate (B0C2O) has been investigated but leads to lower yields in comparison.20... 

In another example of the use of the Staudinger reduction toward the synthesis of medicinally active compounds, Danishefsky s group treated advanced intermediate 57 with trimethylphosphine and water in THF to afford epothilone analog 58 in 79% yield. This... 

The Staudinger reduction has found its way into the synthesis of many biologically relevant molecules in both academia and industry. The following example, published in 2004 from scientists at Abbott Laboratories, comes from their work toward synthesizing new famesyltransferase inhibitors. Quinolone 62 is one example from this publication.29 In the synthesis of this particular inhibitor, bromide 59 was reacted with sodium azide to afford the corresponding azide in 70% yield. Addition of an excess of triphenylphosphine to compound 60 in refluxing THF/H2O delivered the desired amine 61 in 83% yield. Reductive animation then afforded the final target compound 62. 

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