N‐Heterocyclic Carbene Copper(I) Rotaxanes Mediate Sequential Click Ligations with All Reagents Premixed

Abstract

We have prepared NHC‐CuI complexes with a rotaxane structure and used them as sterically sensitive catalysts for one‐pot sequential copper‐catalyzed azide/alkyne cycloadditions in solutions containing all of the coupling partners premixed in unprotected form. Most notably, a photolabile and sterically encumbered complex first catalyzed the coupling of a less bulky azide/alkyne pair; after removing the protective macrocyclic component from the rotaxane structure, through irradiation with light, the exposed dumbbell‐shaped NHC‐CuI complex catalyzed the second click reaction of a bulkier azide/alkyne pair. Using this approach, we obtained predominantly, from a single sealed pot, a bis‐triazole product (84 %) from a mixture of two sterically distinct azides and a diyne.

Azides in the Synthesis of Various Heterocycles

“…Therefore, a heating mixture of the non-bulky alkyne 105, the bulky alkyne 106, the nonbulky azide 107, and the bulky azide 108 in THF at 323 K for 48 h in the presence of rotaxane 1-TFPB (15 mol%), four possible triazole products were formed 109-112 with good selectivity. The triazole 109 was predominant, with the ratio of the triazoles 109-112 being 14:1:0:0 (Scheme 51) [40].…”

“…Therefore, a heating mixture of the non-bulky alkyne 105, the bulky alkyne 106, the nonbulky azide 107, and the bulky azide 108 in THF at 323 K for 48 h in the presence of rotaxane 1-TFPB (15 mol%), four possible triazole products were formed 109-112 with good selectivity. The triazole 109 was predominant, with the ratio of the triazoles 109-112 being 14:1:0:0 (Scheme 51) [40]. Moreover, when azides 107 and 108 were reacted with diyne 113, under the same conditions in the presence of rotaxane 1-TFPB (15 mol%) and then adding [Cu(MeCN)4]PF6 and 2,6-lutidine to the intermediate mixture bis-triazole, 114 was isolated in 74% yield (Method A) (Scheme 52).…”

“…Irradiation of this intermediate mixture with light (350 nm, 5 min) cleaved approximately half of the macrocyclic components formed. Heating the resulting mixture (323 K, 12 h) led to the coupling of the bulky pair of alkyne/azide partners and the formation of triazole product 114 in 84% yield (Scheme 52) [40]. Moreover, when azides 107 and 108 were reacted with diyne 113, under the same conditions in the presence of rotaxane 1-TFPB (15 mol%) and then adding [Cu(MeCN) 4 ]PF 6 and 2,6-lutidine to the intermediate mixture bis-triazole, 114 was isolated in 74% yield (Method A) (Scheme 52).…”

“…Irradiation of this intermediate mixture with light (350 nm, 5 min) cleaved approximately half of the macrocyclic components formed. Heating the resulting mixture (323 K, 12 h) led to the coupling of the bulky pair of alkyne/azide partners and the formation of triazole product 114 in 84% yield (Scheme 52) [40].…”

Mechanically Interlocked Catalysts for Asymmetric Synthesis

“…As preceding related background not discussed in this Review, the exciting works on the use of MIMs as organocatalysts and ligands in metal-catalyzed processes in their nonchiral versions should be taken into account. In a similar sense, switchable rotaxane-based catalysts that are able to modify their catalytic activity as response to an external stimulus are also noteworthy .…”