Aza-Wittig coupling

DihydroquinazoHnes have been synthesized by aza-Wittig coupling to form the carbodiimide and subsequent addition of a secondary amine to induce an intramolecular Michael addition of 157 [202], Elements of diversity are therefore added upon treating the iminophosphoranes with isocyanates or thioisocyanates, and upon the subsequent reaction of the carbodiimide with an excess of a secondary amine. 1,4-DihydroquinazoHnes have been prepared using a tetrafunctional scaffold cyclized with aryl isothiocyanates on Rink resin [204],... 

Ponnuswamy and coworkers reported an interesting approach for the multicomponent synthesis of Spiro compounds 101 under solvent-free conditions based on the Staudinger/aza-Wittig coupling/cyclization [65]. The reaction of azides 98, triphenylphosphine, ketones 99, and 2-sulfanylacetic acid 100 under solvent-free conditions and MW irradiation afforded the corresponding spirothiazoUdin-4-ones 101 in excellent yields (92-96%) (Scheme 11.17). 

A. Ponnuswamy, P. Shanmugavelan, S. Nagarajan, M. Sathishkumar, Helv. Chim. Acta 2012, 95, 922-928. The first one-pot, solvent-free, microwave-accelerated, three-component synthesis of spirothiazolidin-4-ones via Staudinger/aza-Wittig coupling/cychzation. 

Ene-nitrile oxidoisoquinolinium betaine 131 was readily prepared from vinyl triflate aldehyde 79 (Scheme 1.14). Palladium-catalyzed cyanation of vinyl triflate 79 with Zn(CN)2 in DMF at 60 °C produced ene-nitrile aldehyde 129 in 85 % yield [54]. Using the previously developed Staudinger-aza-Wittig reduction sequence, aldehyde 129 was coupled with cyclic ketal azide 121 to afford a 79 % yield of amine 130. The cyclic ketal amine 130 was then treated with 9 1 mixture of CH2CI2/TFA to provide ene-nitrile oxidoisoquinolinium betaine 131 in 93 % yield. 

Supported carbodiimides can be produced via aza-Wittig reactions. The example in Scheme 11 shows the reaction of a benzylic azide with triphenyl-phosphine to give an aminophosphorane.31 This was then coupled with phenylisothiocyanate to give the corresponding carbodiimide. 

The intramolecular aza-Wittig reaction of azidothioesters provides a new approach to functionalized thiazolines <07AG(E)2701>. Coupling of protected amino acids 79 with azido thiols 80 provides thioesters 81, which are treated with triphenyl phosphine to afford thiazolines 17 in good yields. Similarly, the bis(thioester) 82 is converted into the bis(thiazoline) 19. These thiazolines are readily oxidized to the corresponding thiazoles (vide supra). 

Fluorous-tagged reagents are very attractive for reactions in which a stoichiometric by-product is formed that is difficult to separate. An example is perfluor-oalkylated triphenylphosphane for use in Wittig and aza-Wittig reactions, where the corresponding phosphane oxide is removed by fluorous extraction [22, 23]. Similarly, fluorous sulfoxide has been employed in Swern oxidations, and fluorous carbodiimide has been used as a coupling reagent [24, 25]. 

In recent years, synthesis of pyrroles has drawn the attention of chemists. Traditional methods used for pyrrole synthesis include the Hantzsch reaction [45] and the Paal-Knorr condensation reaction [46,47], The latter is the most widely used method, which involves the cyclocondensation reaction of 1,4-dicarbonyl compounds with primary amines to produce substituted pyrroles. In addition, there are several methods such as 1,3-dipolar cydoaddition reaction, aza-Wittig reaction, reductive coupling, and titanium-catalyzed hydroamination of diynes. Scheme 1 shows several catalysts used in this type of reaction [44]. 

The aza-[2,3]-Wittig rearrangement route to tetrahydropyridines can be coupled to a Wittig olefination of 2-acylaziridines. BuLi was actually used as the base for the demonstration. ... 

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