Click a la carte: robust semi-orthogonal alkyne protecting groups for multiple successive azide/alkyne cycloadditions

Ibai E. Valverde (1) , Agnès F. Delmas (1) , Vincent Aucagne (1)

1 CBM - Centre de biophysique moléculaire

We herein describe an in-depth screening and systematic comparison of five classical silyl alkyne protective groups, to evaluate their potential in the context of multiple successive copper (I)-catalyzed alkyne-azide cycloadditions (CuAAC). We confirm the relative sensitivity of TMS, especially under CuAAC conditions. The relative robustness of its higher analogues, and the discovery of mild silver-catalyzed deprotection conditions selective for TES compared to DPS or TIPS allowed us to design a strategy allowing three successive CuAAC on a single scaffold, as we have illustrated by the synthesis of a tris-triazolo model compound.

Mots clés: CuAAC; Click chemistry; Protective groups; Iterative cycloadditions; SOLID-PHASE SYNTHESIS; EFFICIENT SYNTHESIS; TRIAZOLE OLIGOMERS; PEPTIDE-SYNTHESIS; TERMINAL ALKYNES; ONE-POT; CHEMISTRY; LIGATION; AZIDES; DNA

Ibai E. Valverde, Agnès F. Delmas, Vincent Aucagne. Click a la carte: robust semi-orthogonal alkyne protecting groups for multiple successive azide/alkyne cycloadditions. Tetrahedron, 2009, 65 (36), pp.7597-7602. ⟨10.1016/j.tet.2009.06.093⟩. ⟨hal-00525398⟩