De Novo Ring-Forming Consecutive Four-Component Syntheses of 4-Pyrazolyl-1,2,3-triazoles from (Triisopropylsilyl)butadiyne as a C4 Building Block

Abstract

4-Pyrazolyl-1,2,3-triazoles can be readily synthesized in a one-pot fashion and moderate yield by employing a consecutive four-component process consisting of a sequentially Pd-Cu-catalyzed alkynylation-cyclocondensation-desilylation-CuAAC process. Most distinctly, (triisopropylsilyl)butadiyne is employed as a four-carbon building block in this one-pot de novo formation of both heterocyclic moieties.

Substituted 1H‐1,2,3‐Triazol‐4‐yl‐1H‐pyrrolo[2,3‐b]pyridines by De Novo One‐Pot Ring‐Forming Coupling/Cyclization/Desilylation Cu Alkyne/Azide Cycloaddition (AAC) Sequence

“…TIPS‐butadiyne ( 3 ) is a suitable four‐carbon building block,, which has been applied in natural‐product synthesis and materials science; however, only in two cases, in multicomponent syntheses …”

“…[13] TIPS-butadiyne (3)i sasuitable four-carbon building block, [11b, 14] which has been applied in natural-product synthesis [15] and materials science; [16] however,o nly in two cases, in multicomponent syntheses. [17,18] In previous attempts to couple 2-amino-3-bromo-5-methylpyridine with 3 in DMSO or 1,4-dioxane using catalytic amountso f[ Pd(PPh 3 ) 4 ]a nd CuI, only trace amounts of coupling product could be observed, even when using reaction times of up to 16 hours and reaction temperatures of up to 100 8C. Therefore, 2-amino-5-chloro-3-iodopyridine was first identified as as ufficiently reactive substrate for the alkynylation step.…”

Acyl Sonogashira Cross-Coupling: State of the Art and Application to the Synthesis of Heterocyclic Compounds

“…However, very recently they also developed a more interesting one-pot synthesis of 5-triazolyl-substituted-1Hpyrazoles; in this case, the acyl Sonogashira step was performed between acyl chlorides and Along the lines of the last two mentioned works, in 2015 a four-component preparation of 1-, 3-or 5-biaryl-substituted-1H-pyrazoles was reported by Müller et al, following a sequential acyl Sonogashira coupling/Michael addition-cyclocondensation/Suzuki-Miyaura coupling [73]. However, very recently they also developed a more interesting one-pot synthesis of 5-triazolyl-substituted-1H-pyrazoles; in this case, the acyl Sonogashira step was performed between acyl chlorides and triisopropylsilyl (TIPS)-protected butadiyne, giving the corresponding TIPS-protected pentadiynones; upon cyclocondensation with methyl or benzyl hydrazine, 5-TIPS-ethynyl-1H-pyrazoles were generated, which gave final compounds after tetra-n-butylammonium fluoride (TBAF) promoted desilylation, followed by copper(I)-catalyzed alkyne− azide cycloaddition (CuAAC) with benzyl, homobenzyl or (hetero)aryl azides (Scheme 26) [27]. triisopropylsilyl (TIPS)-protected butadiyne, giving the corresponding TIPS-protected pentadiynones; upon cyclocondensation with methyl or benzyl hydrazine, 5-TIPS-ethynyl-1H-pyrazoles were generated, which gave final compounds after tetra-n-butylammonium fluoride (TBAF) promoted desilylation, followed by copper(I)-catalyzed alkyne− azide cycloaddition (CuAAC) with benzyl, homobenzyl or (hetero)aryl azides (Scheme 26) [27].…”

“…However, very recently they also developed a more interesting one-pot synthesis of 5-triazolyl-substituted-1H-pyrazoles; in this case, the acyl Sonogashira step was performed between acyl chlorides and triisopropylsilyl (TIPS)-protected butadiyne, giving the corresponding TIPS-protected pentadiynones; upon cyclocondensation with methyl or benzyl hydrazine, 5-TIPS-ethynyl-1H-pyrazoles were generated, which gave final compounds after tetra-n-butylammonium fluoride (TBAF) promoted desilylation, followed by copper(I)-catalyzed alkyne− azide cycloaddition (CuAAC) with benzyl, homobenzyl or (hetero)aryl azides (Scheme 26) [27]. triisopropylsilyl (TIPS)-protected butadiyne, giving the corresponding TIPS-protected pentadiynones; upon cyclocondensation with methyl or benzyl hydrazine, 5-TIPS-ethynyl-1H-pyrazoles were generated, which gave final compounds after tetra-n-butylammonium fluoride (TBAF) promoted desilylation, followed by copper(I)-catalyzed alkyne− azide cycloaddition (CuAAC) with benzyl, homobenzyl or (hetero)aryl azides (Scheme 26) [27]. In all the above described synthetic routes to pyrazoles, the acyl Sonogashira step has been performed by using PdCl2(PPh3)2 as catalyst and CuI as the co-catalyst.…”

“…Catalysts 2019, 9, x FOR PEER REVIEW 17 of 35 triisopropylsilyl (TIPS)-protected butadiyne, giving the corresponding TIPS-protected pentadiynones; upon cyclocondensation with methyl or benzyl hydrazine, 5-TIPS-ethynyl-1H-pyrazoles were generated, which gave final compounds after tetra-n-butylammonium fluoride (TBAF) promoted desilylation, followed by copper(I)-catalyzed alkyne− azide cycloaddition (CuAAC) with benzyl, homobenzyl or (hetero)aryl azides (Scheme 26) [27]. In all the above described synthetic routes to pyrazoles, the acyl Sonogashira step has been performed by using PdCl2(PPh3)2 as catalyst and CuI as the co-catalyst.…”