Enediyne sulfonamides

Klein, M. Konig, B. Synthesis and thermal cyclization of an enediyne-sulfonamide. Tetrahedron 2004, 60, 1087-1092. 

Cyclic enediyne sulfonamides 3.849 and 3.850 (Figure 3.9) have certain advantages over carbon and sulfur analogs in the cycloaromatization... 

In a study on the activation of macrocyclic enediynes by transannular cyclization it was found that the deprotection of the sulfonamide group of ketone 91 triggered the formation of aminol 92 which readily provided the isoquinoline derivative 93 via a Bergman cyclization reaction <04AG(E)132>. 

Interestingly, when the substrate was switched from benzene-1,2-dialkyne 90 to cA-enediyne 95, 6-endo-dig cyclization reaction pathway was observed. Two regioisomeric ort/zo-auroaryl cation intermediates 96 and 98 were proposed via dual gold-catalyzed 6-endo-dig cyclization model, which can be mutual isomerization via aryne-coordinated gold complex 97. Ort/zo-aurophenyl cation intermediates 98 could be trapped by a tethered hydroxy or sulfonamide group to deliver the seven-membered O- or AT-heterocycles 99 (Scheme 12.45) [48]. 

There are several examples of enediyne activation by a sulfonamide group. The thermal cyclization of N-benzyl-N-[(2-ethynylphenyl) ethynyl]-4-methylbenzene-sulphonamide 3.835 gives N-benzyl-N-naphth-2-yl-4-methylbenzenesulphonamide 3.836 (141°C, benzene/1,4-cyclohexadiene = 2 1) (Scheme 3.108) [382] It simultaneously lowers the sensitivity of the ynamine fragment to hydrolysis [383]. This confirms the general rule that the a-acceptor substituents at the terminal acetylene atom of enediyne increases its propensity to cycloaromatization. 

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