Iodoalkyne‐Based Catalyst‐Mediated Activation of Thioamides through Halogen Bonding

Abstract

Halogen bonding catalysis has recently gained increasing attention as a powerful tool to activate organic molecules. However, the variety of the catalyst structure has been quite limited so far. Herein, we report the first example of the use of an iodoalkyne as a halogen bond donor catalyst. By using an iodoalkyne bearing a pentafluorophenyl group as a catalyst, thioamides were efficiently activated and reacted with 2-aminophenol to generate benzoxazoles in good yield. Mechanistic studies, including C NMR spectroscopic analysis and several control experiments, provided concrete evidence that this catalytic activation is based on halogen bonding. Thus, the results obtained in this study demonstrate that iodoalkynes can serve as a new scaffold for future development of halogen bonding catalysis.

Halogen Bonding in Solution: Anion Recognition, Templated Self‐Assembly, and Organocatalysis

“…Thefirst report of the use of the neutral iodoalkyne motif as aX B-based activator (28)w as published in 2016 and described the effective activation of thioamides and their subsequent conversion into benzoxazoles (Figure 20). [70] This study underlined the advantages of neutral XB donors over charge-assisted systems,n amely,t heir better solubility in organic solvents as well as their higher stability towards nucleophiles and elevated temperatures.Control experiments with the analogous terminal alkyne as well as with the trimethylsilyl-protected system revealed product yields comparable to that obtained in the absence of the catalyst and, thus,f urther support the XB-mediated activation of the substrate.…”

Direct N‐Glycofunctionalization of Amides with Glycosyl Trichloroacetimidate by Thiourea/Halogen Bond Donor Co‐Catalysis

“…[12c] Although thiourea have been recently employed for glycosylation [11] and acetalization [13] of alcohols, its acidity was insufficient to activate trichloroacetimidate. [11a,b] We envisioned that asoft and mild Lewis acid, such as 2-iodoazolium salt [14] (R 2 ¼ 6 H) as halogen bond (XB) donor, [15][16][17] used as ac o-catalyst would interact with the soft Lewis basic moiety of thiourea [18] to increase the HB-donating ability of thiourea, [19] so that the LG could be activated [20] with wide functional group tolerance.The produced N-acylorthoamides [21] would serve as intermediates for thermodynamically favored b-N-glycosides [10] (Scheme 1a,p ath d, Nu = amide), and offer au nique traceless N-glycofunctionalization of amide,i mpacting on prodrug synthesis.I nf act, during the course of our investigation on the rearrangement of Nacylorthoamide to N-glycoside (path d), we have developed an ew type of Brønsted-acid-salt catalyst, comprised of Brønsted acid and 2-halogenated azole,w hich was found to be an efficient catalyst for the direct N-glycosylation of various amides using the same glycosyl trichloroacetimidates (path band/or paths aa nd d).…”

Electrophilic Activation of Iodonium Ylides by Halogen‐Bond‐Donor Catalysis for Cross‐Enolate Coupling

“…[6] Many approaches have been investigated for the synthesis of these important synthetic intermediates; [7][8][9][10] however,t he activation of the iodonium ylide seems to be the most challenging aspect of such ah ypothetical reaction. [16,17] We envisaged that the soft Lewis acidity of XB donors [18][19][20] would allow them to preferentially interact with soft electrophiles (Scheme 1c). [1,5] We thus focused on halogen bonding (XB), which is anoncovalent interaction between halogenated compounds and Lewis bases.…”

“…[1,5] We thus focused on halogen bonding (XB), which is anoncovalent interaction between halogenated compounds and Lewis bases. [16,17] We envisaged that the soft Lewis acidity of XB donors [18][19][20] would allow them to preferentially interact with soft electrophiles (Scheme 1c). [16,17] We envisaged that the soft Lewis acidity of XB donors [18][19][20] would allow them to preferentially interact with soft electrophiles (Scheme 1c).…”

“…[12] Although XB donors have recently begun to be used in synthetic organic chemistry as easy-to-handle organic Lewis acids, [13] their activation mode is mainly limited to the sp 2 -hybridized nitrogen atoms of quinolines and imines, [14] carbonyl oxygen atoms, [15] and alkyl halides. [16,17] We envisaged that the soft Lewis acidity of XB donors [18][19][20] would allow them to preferentially interact with soft electrophiles (Scheme 1c). Herein, we report the first efficient electrophilic activation of iodonium(III) ylides for which an XB donor was found to be effective.I na ddition, we have developed the first XB donor/Brønsted base cooperative catalytic system, which enabled the in situ formation of the nucleophilic component without deactivation of the XB donor catalyst.First, we studied the interaction between XB donors and iodonium ylide 2a [21] in the reaction of 2a with silyl enol ether 1a as ap reactivated nucleophile (Table 1).…”