Synthesis of 1,2,3-Triazolo-Fused Allocolchicine Analogs via Intramolecular Oxidative Biaryl Coupling

Abstract

A novel series of 1,2,3-triazolo-fused allocolchicine analogs is described. The strategy to prepare these analogs involves two steps: The first step is the synthesis of 1,2,3-triazole derivatives using our previously reported triazolization method, and in the second step, cyclization between two aromatic rings occurs by using the combination of PIFA and BF3·Et2O as an oxidative coupling reagent. Furthermore, the diversity of aromatic rings and functional groups is explored in order to obtain seven- and eight-membered ring systems with medicinal chemistry interest.

Progress in the Synthesis of Fused 1,2,3‐Triazoles

“…Krasniqi and Dehaen employed intramolecular oxidative biaryl coupling to synthesize fused triazoles 353 using PIFA and BF 3 .OEt 2 as efficient oxidative coupling agent (Scheme 111). [111a] 1,2,3‐triazole intermediates 352 were synthesized by their previous reported triazolization methodology [111b] . Oxidizing systems such as DDQ/TFA, Cloranil/ BF 3 .OEt 2 , MnO 2 / BF 3 .OEt 2 did not provide the product.…”

Triazolization of Enolizable Ketones with Primary Amines: A General Strategy toward Multifunctional 1,2,3‐Triazoles

“…A third post‐triazolization cyclization reaction was the oxidative coupling between two aryl moieties interconnected by a 1,5‐disubstituted 1,2,3‐triazole, and led to fused seven‐ and eight‐membered ring systems (Scheme 10). [54] Among the different methods screened, only a combination of phenyliodine bis(trifluoroacetate) (PIFA) and BF 3 ⋅OEt 2 could facilitate the biaryl coupling in a good yield. Next, different triazolization products 32 were subjected to the optimal reaction condition.…”

“…In the years after the first report, the procedure has been adapted in order to broaden the scope with respect to the amines and ketones [46–49] . Moreover, triazolization products found applicability in the large‐scale preparation of triazolium‐based ionic liquids, [50,51] in several cyclization strategies [52–55] and as potential antiviral or anticancer agents [56–59] . In this highlight, the triazolization reaction along with its modifications will be discussed.…”

5-Formyltriazoles as Valuable Starting Materials for Unsymmetrically Substituted Bi-1,2,3-Triazoles

“…The lack of investigation in this area could be ascribed to the complicated syntheses of both starting materials (functionalized alkynes) and bi-1,2,3triazoles themselves, and hence the cumbersome introduction of functional groups interesting for various applications (Zheng et al, 2015;Dawood et al, 2018). In regard with our current interests in sterically encumbered fully substituted (atropisomeric) 1,2,3-triazoles (Thomas et al, 2014(Thomas et al, , 2016Vroemans et al, 2018;Krasniqi and Dehaen, 2019), we report what are to the best of our knowledge the first pathways toward novel unsymmetrically tetra-ortho-substituted 5,5 ′ -bi-1,2,3triazoles from easily accessible starting materials. The anticipated highly sterically hindered bi-1,2,3-triazoles could be decorated with various functional groups which can be introduced in a straightforward manner from ortho, ortho'(1,4-)-disubstituted 5-formyl-1,2,3-triazoles, and nitroalkane derivatives.…”