A New Multicomponent Multicatalyst Reaction (MC)²R: Chemoselective Cycloaddition and Latent Catalyst Activation for the Synthesis of Fully Substituted 1,2,3-Triazoles

Abstract

A multicomponent multicatalyst reaction (MC)(2)R for constructing fully substituted 1,2,3-triazoles is reported. An application of chemoselectivity and latent catalysis in a sequence of multicatalytic reactions confers control over a number of undesired processes, where all of the reagents coexist in the same reaction vessel. The sequence of a chemoselective copper-catalyzed azide alkyne cycloaddition followed by a palladium/copper-catalyzed Sonogashira cross-coupling afforded 1,2,3-triazoles regioselectively with good to high yields and a broad scope.

Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications

“…278 This triazole is subsequently alkylated on the 5-position and deprotected to finally afford the 1,5-isomer. Lautens used a combination of Cu and Pd in a tandem reaction to form 1,4,5-trisubstituted triazoles, 279 while Greaney has reported a Zn-mediated synthesis of 1,5-and 1,4,5-isomers. 280 1,5-Disubstituted 1,2,3-triazoles can also be formed without the use of a metal.…”

Palladium‐Catalyzed Cascade Cyclization/Alkynylation Reactions

“…Lautens and co‐workers described a new multicomponent multicatalyst reaction for the synthesis of fully substituted 1,2,3‐triazole derivatives ( 67 ) from readily available alkynes and azides (Scheme ) . A series of aliphatic/ aromatic azides reacted with alkynes to give the fully substituted 1,2,3‐triazoles in moderate to good yields.…”

“…Lautensa nd co-workers described an ew multicomponent multicatalyst reactionf or the synthesis of fully substituted 1,2,3-triazole derivatives (67)f rom readily availablea lkynes and azides (Scheme35). [66] As eries of aliphatic/a romatic azides reacted with alkynes to give the fully substituted 1,2,3-triazoles in moderate to good yields. Am echanism involvings equential copperc atalyzed azide alkyne cycloaddition and palladium/ copper-catalyzed Sonogashira coupling reaction has been presumed for this cascade alkynylation process.…”

Intramolecular Copper(I)‐Catalyzed Interrupted Click–Acylation Domino Reaction

“…Thep aucity of methodologies to readily access these molecular structures is surprising given that 5-acyl-1,4,5-trisubstituted triazoles such as those in Scheme 1p ossess valuable biological activity. [12] Thei nterruption of the CuAACw ith an electrophilic species has not received the same level of attention despite the fact that this strategy would represent the most direct approach towards the fully substituted 1,2,3-triazole scaffold (Scheme 2a). [11] Alternative methods of achieving fully substituted triazoles have relied on the combination of expensive transition metal-catalyzed cross couplings and CuAACsequences.…”

“…compounds relies on the non-regiospecific non-copper catalyzed 1,3-cycloaddition which is performed under extremely harsh conditions. Other ligands and copper sources led to inferior results (entries [11][12][13][14]. This approach also represents an ovel example of an interrupted click-acylation domino process leading to aheterocycle.…”