Azido thioethers

An acyclic azide structure was rejected since the compounds show no azide IR absorption. A less likely three-membered ring was also considered. Comparison with other potential dihydro-SIV-thiatriazoles was made. Simple a-azido thioethers show the spectroscopic and chemical properties of azides rather than of dihydro-Slv-thiatriazoles. o-(Methylthio)phenyl azide was prepared but also showed the characteristics of an azide.70 These results cast doubt on the suggested structure, since the only essential difference in composition is an amino group that is not in a position to stabilize the suggested heterocyclic ring. Structure R1(R3R4N)C=N—N=N—SR2 is an alternative, but. further consideration must await X-ray crystallographic analysis. 

The first total synthesis of the potent cytotoxic marine natural product makaluvamine F (5) involved the preparation of 2,3-dihydrobenzothiophene 2 <99CC143>. Debenzylation and subsequent acid-catalyzed cyclization of thioether 1 gave 2 which was converted in four steps to 2-azido-2,3-dihydrobenzothiophene 3 using a combination of Phl=0 and McjSiNj for installation of the azide. Reduction of the azide followed by coupling the resultant amine with pyrroloiminoquinone 4 then gave makaluvamine F (5). 

The report by Lieber and co-workers discusses such diverse classes of azides as acyl azides, carbamyl azides, vinyl azides, and a-azido ethers, thioethers and amines. None of these violates the limits of the asymmetric stretching frequency cited earlier. 

Villalgordo et al. [22, 23] as well as Gayo and Suto [25] developed a strategy to cleave pyrimidines from the solid support. After oxidation of the thioether-linkage 17, aromatic substitution of the sulfonyl unit was performed with different N-nucleophiles as amines and azides to give free amino- or azido-pyrimidines 19 (Scheme 16.5). To demonstrate the stability of the linker, the resin-bound derivatives were subjected to different reactions such as saponification, ester reduction, acid chloride formation or Mitsunobu alkylation. A similar approach was presented later on by Hwang and Gong in the SPOS of 2-aminobenzoxazoles [26]. 

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