Staudinger reaction heterocyclic synthesis

Staudinger reaction (phosphazene synthesis and reactions with a special focus on the aza-Wittig process)and reviews of the applications of the aza-Wittig reaction to heterocyclic... 

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... 

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-... 

Recently, the ability of N-heterocyclic carbenes to promote the Staudinger reaction has been investigated using ionic liquids, in the presence of suitable base as pre-catalysts. According to the procedure suggested by Smith et al., a solution of base (potassium hexamethyldisilazide KHMDS, toluene as solvent) was added to the suspension of ionic liquid (triazolium salt) in Et O and stirred under N. Subsequently, the mixture was added of diphenylketene and of imine and stirred at room temperature before concentration in vacuo (Scheme 16.6). The order of addition of reactants is critical for the success of the synthesis [95]. 

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. 

Since its discovery in 1907, the Staudinger reaction is one of the most useful methods for the synthesis of p-lactams (2-oxazetidinones) [77,78]. The importance of these strained heterocycles relies not only on the chemical synthesis of 3-lactam antibiotics [79] but also on other valuable compounds in medicinal chemistry [80] such as the acyclic chain of taxol and bestatin [81] or ecteinascidin-743 (Scheme 2.4) [82]. 

Meyers and co-workers have continued their studies to exploit the synthetic potential of a-lithio-formamidines and have now described an efficient synthesis of 2-aryl- or 2-heteroaryl-pyrrolidines and -piperidines (266 ). " Alkylation of formamidines (264) gives intermediates (265) which cyclize in situ after cleavage of the amidine unit. The aza-Wittig reaction has been utilized in a general synthesis of heterocyclic vinylogous ure-thanes and amides (268). Staudinger reaction of azides (267)... 

Another useful synthetic method for the synthesis of complex heterocyclic compounds is the aza-Wittig reaction, involving carbodiimides as intermediates. This reaction was discovered by Staudinger and Hauser in 1921. Carbodiimides have also found use as agricultural chemicals and pharmaceutical intermediates. For example. 

Progress in the synthesis of heterocyclic natural products by the Staudinger/intramolecular aza-Wittig reaction 05ARK(2)98. 

Professor Hermann Staudinger first reported the reaction in 1907, as part of an overall study on the chemistry of ketenes carried out at the University of Strassburg. His discovery remained largely overlooked until the emergence of penicillin and other p-lactams as antibiotics during World War II. Since then, other classes of P-lactam antibiotics have been developed, and the P-lactams are still widely used to treat infection. After over 100 years, this general reaction yielding P-lactams remains one of the key methods for the synthesis of these strained heterocycles, which remain important in both medicinal and synthetic chemistry. ... 

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