Alkynylation with Hypervalent Iodine Reagents

Abstract

Alkynes are among the most versatile functional groups in organic synthesis. They are also frequently used in chemical biology and materials science. Whereas alkynes are traditionally added as nucleophiles into organic molecules, hypervalent iodine reagents offer a unique opportunity for the development of electrophilic alkyne synthons. Since 1985, alkynyliodonium salts have been intensively used for the alkynylation of nucleophiles, in particular soft carbon nucleophiles and heteroatoms. They have made especially a strong impact in the synthesis of highly useful ynamides. Nevertheless, their use has been limited by their instability. Since 2009, more stable ethynylbenziodoxol(on)e (EBX) reagents have been discovered as superior electrophilic alkyne synthons in many transformations. They can be used for the alkynylation of acidic C-H bonds with bases or aromatic C-H bonds using transition metal catalysts. They were also highly successful for the functionalization of radicals or transition metal-catalyzed domino processes. Finally, they allowed the alkynylation of a further range of heteroatom nucleophiles, especially thiols, under exceptionally mild conditions. With these recent discoveries, hypervalent iodine reagents have definitively demonstrated their utility for the efficient synthesis of alkynes based on non-classical disconnections.

Ligand-Promoted meta-C–H Amination and Alkynylation

“…16 Consequently, installation of alkyne groups via C–H alkynylation has attracted significant interest and has been studied using terminal alkynes, 17 alkynyl halides, 18 and hypervalent iodine reagents. 19 However, meta -C‒H alkynylation has not been reported to date. The lack of precedents using alkynyl coupling partners as electrophiles in the Catellani reaction also attests to the challenge of developing meta -C‒H alkynylation using norbornene as a transient mediator.…”

Iron‐Catalyzed C−H Alkynylation through Triazole Assistance: Expedient Access to Bioactive Heterocycles

“…[1,2] As ac onsequence,t he development of efficient strategies for the construction of alkynes continues to be an importantg oal, often being achieved by the conventionalS onogashira-Hagihara cross-coupling reaction. [3] However,o ver the last decade, transition-metal catalyzed CÀHf unctionalization has emerged as ap owerful alternative for the direct introduction of the alkynyl moiety. [4] Thus, efficient and valuable methods have been realized with the aid of expensive 4d and 5d transition metals.…”

Practical Synthesis of Ethynyl(phenyl)-λ3-Iodane Using Calcium Carbide as an Ethynyl Group Source

“…Hypervalent ethynyl(phenyl)-λ 3 -iodane 1 is an efficient electrophilic ethynylating agent for a variety of nucleophiles (C, N, O, P, As, S, Se, and halides) in the presence or absence of transition metal catalysts (Figure 1A; Ochiai et al, 1990;Varvoglis, 1992;Ochiai, 2003;Waser, 2016;Yoshimura and Zhdankin, 2016). However, its synthetic utility is restricted by its high cost and heat/moisture-sensitive character: it gradually decomposes at room temperature in air Yudasaka et al, 2019).…”