Phosphine oxide Staudinger reaction

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.

The phosphides and arsenides of the elements M—PRR and M—AsRR are well known for main group elements, but transition metal analogues are more unusual. Insertion reactions were not widely explored until recently, but examples are given in reactions (j) and (k) (X = O or S) ° and (l) (n) (X = or As ) and (m) are effectively oxidative insertions of a nitrene, or specifically PhN into an Sn-P or Sn-As bond, and thus represent an extension of the Staudinger reactions whereby a phosphine or arsine is treated with an azide, and thereby converted into a phosphine-imine or the arsine analogue, as follows ... 

Mitsunobu and Staudinger reactions. The ligand is superior triphenylphosphine because the phosphine oxide by-product is easily removed. 

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. 

If the Staudinger reaction of an alkyl azide containing a pendant carbonyl group is heated under anhydrous conditions, the iminophosphorane can nucleophilically attack the carbonyl leading to cyclic imines (via the aza-Wittig mechanism) and liberate phosphine oxide as shown below. The reaction also works intermolecularly. 

Phosphinimines. A simple preparation of RjP=NH from a phosphine oxide involves the evaporation of a mixture of it with Tf O and NH3. The process is repeated several times. Access to these unsubstituted imines by the Staudinger reaction is difficult, because the imines are hygroscopic and hydrolyzable. 

Treatment of enecarbamate 344 with sodium azide and ceric ammonium nitrate (CAN) in acetone furnished azidocarbazole 345. The low yield in this oxidative cychzation reaction is due to formation of the diastereomer consisting of stereochemical inversion at the azide-substituted carbon. At this point, azide reduction employing the Staudinger conditions of triphenyl-phosphine in a mixture of water and THF led to an amine, which was subjected to trichloroacetyl chloride in a solution of dichloromethane and triethylamine to yield amide 346 (Scheme 49). 

A special variant of resolution is called oxidative resolution, because it yields optically pure phosphine oxides from racemic phosphines. To this end, Keay and co-workers" used the Staudinger reaction between racemic phosphines and an optically pure azide (Scheme 2.3). 

---