Staudinger reaction amines

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... 

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. 

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). 

The Kirsanov reaction (Scheme 5) is a valuable supplement to the Staudinger reaction starting from phosphorus pentachloride and amine or amide derivatives it opens an access to P-halogenated iminophosphorane 9 (50IZV426). 

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

Trifluoroalanine has also been prepared by reducing trifluoropyruvate imines (ethyl trifluoropyruvate is available commercially it is prepared either from per-fluoropropene oxide or by trifluoromethylation of ethyl or f-butyl oxalate). These imines are obtained by dehydration of the corresponding aminals or by Staudinger reaction. They can also be obtained by palladium-catalyzed carbonylation of trifluoroacetamidoyl iodide, an easily accessible compound (cf. Chapter 3) (Figure 5.4). Reduction of the imines affords protected trifluoroalanines. When the imine is derived from a-phenyl ethyl amine, an intramolecular hydride transfer affords the regioisomer imine, which can further be hydrolyzed into trifluoroalanine. ... 

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... 

An alternative route starting from serine 73 or threonine 68 74 makes use of diethoxy-triphenylphosphorane. Attempts to asymmetrically synthesize (25)-aziridine-2-carboxylic acid (1) by treating a, 3-dibromopropanoates with chiral amines 75 or by the Staudinger reaction from oxirane-2-carboxylic acid ester 70,76 leads to optically impure products, whereas 3-alkyl derivatives of tert-butyl aziridine-2-carboxylates can be prepared with high cis-selectivity from a-halo ester enolates and jV-trimethylsilyl imines. 77 Moreover, when optically... 

The Staudinger reaction between optically active acid chloride 161 and A-benzyl-A-[(l ,)-phenylmethylene] amine in the presence of triethylamine in dichloromethane resulted in the formation of two diastereomerically pure spiro-(3-lactams 162 (51%), 163 (20%) as single enantiomers in each case. The spiro-(3-lactams 162, 163 were further transformed to proline-derived spiro-(3-lactams 165, 167 via elimination of methanesulfonic acid using K2C03/Me0H and... 

In 2000, the group of Banik et al. reported the enantiospecific synthesis of 3-hydroxy-2-azetidinones by microwave assisted Staudinger reaction [51]. Chiral imines, derived from chiral aldehydes and achiral amines, reacted with methoxy- or acet-oxy-acetyl chloride to afford a single, optically pure c/s-p-lactam, (Scheme 7). 

Scheme 12 Resin-supported free amine and subsequent Staudinger reaction...

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. 

The role of some chiral bifunctional amines and optically active cinchona alkaloid derivatives (Figure 3) as catalysts has been explored in catalytic asymmetric Staudinger reactions. Bicarbonate salts have been used as viable alternatives to... 

Dehydrohalogenation of substituted acetyl chlorides via tertiary organic bases and the stereoselective construction of an azetidinone ring from an imine (the Staudinger reaction) has played an important part in the development of azetidinone chemistry, which has been reviewed <1993MI637>. The use of bicarbonates in the presence of a crown ether at — 10°C has been suggested as an economical alternative to tertiary amines <2003SL1937>. 

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>. 

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

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