Nitrogen Staudinger reaction

In the first step, the triphenylphosphine reacts with an alkyl azide to form an iminophosphorane with loss of nitrogen Staudinger reaction). In the second step, the nucleophilic nitrogen of the iminophosphorane attacks the carbonyl group to form a four-membered intermediate (oxazaphosphetane) from which the product Schiff base and the byproduct triphenylphosphine oxide are released. 

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... 

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). 

The Staudinger reaction of imines 481 derived from 7-oxanorbornenone with arylacetic acid chlorides 482 furnished a 0-40 60-100 mixture of C-2-epimeric, spiro-condensed l,3-oxazin+-one derivatives 483 and 484, the ratio of which proved to depend on the substituents on the aromatic rings and on the nitrogen atom (Equation 54) <2002TL6405>. 

The reaction of iV-benzyloxycarbonyl L-proline acid chlorides 134 with imine 135 in the presence of triethylamine, at room temperature, gave the corresponding spiro-(3-lactams 136, 137 as a 1 1 mixture of diastereoisomers, which were separated by column chromatography. The Staudinger reaction proceeds with complete stereoselectivity with a cis relative disposition of the pyrrolidine nitrogen and the phenyl group, but no asymmetric induction was observed. However, very... 

The stereochemistry of the Staudinger reaction was highlighted [86] using as substrates polyaromatic imines and acetoxy, phenoxy, or phthalimido acid chloride. The stereochemistry of the resulting p-lactams seemed to vary depending on the substituents present in the imines and the acid chlorides. For instance, if the polyaromatic moiety was linked to the iminic nitrogen, the reaction produced //Y/n.v-p-lactams if the same moiety was linked to the iminic carbon, cA-p-lactams were isolated. 

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... 

The compounds of this class, mostly silyl derivatives (R = SiMes), prepared by Staudinger reactions from the corresponding diphosphines and silyl azides (Scheme 39), received recent attention owing to their versatility as nitrogen-donor ligands. ... 

An alternative elegant native ligation approach has recently been proposed where the Staudinger reaction is exploited to couple the carboxy component as a thioester via trans-thioesterification to a suitable phosphine scaffold that reacts with azidoacyl peptides to produce the imino-X, -phosphine. This chemical ligation is followed by nucleophilic attack by the imino-X -phosphine nitrogen on the thioester to form the amide bondt °°l (Section 2.2.1.10). 

In an attempt to prepare a phosphathiosemicarbazide (159) the diphosphine monosulphide (160) was obtained instead. This surprising result was explained by attack of the jhlorophosphine at sulphur instead of at nitrogen as shown. Another unexpected result was the attempted Staudinger reaction of trimethylsilyl azide with (161) which gave (162) the reaction is probably initiated by azide attack at the thiocarbonyl group in preference to the phosphorus atom. 

Molina and co-workers continue to develop their work on the synthesis of nitrogen-containing heterocycles using the aza-Wittig reaction. Recent developments, include studies into the synthesis and reactivity of phosphazides (109) (Scheme 22) which were obtained from the Staudinger reaction of an N-... 

Interest in the Staudinger reaction of phosphines with azides, and the Mit-sunobu reaction involving nucleophilic attack by phosphorus at nitrogen in esters of diazodicarboxylic acids, has continued. Systems of the type (205) have been obtained from the reactions of secondary arylphosphines with azides. Treatment of these with butyllithium results in deprotonation to form the diaminophosphonium diazaylides (206). Phosphazenes have been prepared from azido-quinolines and -triazines, and also from diazoketones " and polycyanocyclopropanes. The Staudinger reaction has been employed in the synthesis of phosphorus-containing dendrimers, and in new approaches to amide and peptide synthesis. The reaction has also been used in a high-... 

The laboratories of Stec (24) and the author (26-28) have reported that the nitrogen anions of phosphoramidates react with carbonyl compounds (benzalde-hyde or CO2) to incorporate an atom of oxygen bonded to phosphorus at the expense of the nitrogen substituent, and that this reaction proceeds with retention of configuration at phosphorus. This stereochemically useful reaction, known as the Wittig-Staudinger reaction, is not limited to carbonyl compounds but can also be used with thiocarbonyls or selenocarbonyls to produce chiral phospho-rothioates or phosphoroselenates with retention of configuration at phosphorus (27). The primary application of this reaction has been in the preparation of both... 

Under strictly anhydrous conditions, the iminophosphorane intermediate that is formed as a result of the Staudinger reaction can react with aldehydes and ketones in an intermolecular fashion (as in the synthesis of imine 36 described above) or intramolecularly with a variety of carbonyl containing functional groups to afford a host of products. Nitrogen containing ring systems such as cyclic imines (44) represent just one of the many products one can prepare and the reaction is particularly well suited for the facile synthesis of five, six, and seven-membered rings. In addition to aldehydes and ketones, carboxylic acids, esters, thio-esters, and amides can also react in an intramolecular fashion to trap an iminophosphorane to afford a variety of heterocycles. Examples from the current literature are described in Section 2.5.5. 

Nucleophilic attack at nitrogen has also been identified in a study of the reactions of triarylphosphines with tetracyanoethylene in aqueous acetonitrile. In contrast, the related reactions with tetracyanoquinodimethane (TCNQ) involve one electron transfer from phosphorus to the TCNQ molecule. Full details of the reactions of tertiary and ditertiary phosphines with bromophenyldiazirines have now appeared. Interest in the Staudinger reaction of tertiary phosphines with azides has also been maintained. A spectroscopic study has shown that the sequence of addition of reactants alters the course of the Staudinger reaction of azides in the presence of acyl derivatives. The Staudinger reaction of a-azidophenylacetonitrile with triphenylphosphine unexpectedly results in the formation of the salt (135). Applications of the Staudinger reaction in synthesis... 

Recent advances in the Staudinger reaction of tertiary phosphines with azido compounds have been reviewed.The reaction of the alkynylphosphine (88) with phenylazide yields the unstable intermediate (89), which in the presence of protic substances undergoes nucleophilic addition to the triple bond. The reactivity of the nitrogen-silicon bond of the phosphinimine derived from triphenylphosphine and trimethylsilylazide has been exploited in reactions with chloroformyl reagents to generate new functionalised phosphinimines, e.g., (90). ... 

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