Alkynylations and Vinylations

Abstract

Alkynes and alkenes are important building blocks in synthetic organic chemistry and related domains. Therefore, unceasing efforts have been invested to develop new methods to introduce these valuable functional groups. Traditionally, most alkynylation and alkenylation reactions have relied on the use of olefins and acetylenes as nucleophilic reacting species, limiting the accessible structural diversity. The discovery of the unique properties of hypervalent iodine has more recently significantly broadened the scope of electrophilic ethynylation and vinylation reactions. Alkynyl and alkenyl iodonium salts were first recognized as powerful reagents to install electrophilic acetylenes and olefins onto nucleophilic substrates under mild conditions. Their low stability has however narrowed the area of their applications. Since 2009, more stable cyclic benziodoxol(on)e reagents have shown their superiority as effective electrophilic alkynylating and alkenylating reagents in numerous metal-free and metal-catalyzed olefination and ethynylation reactions of carbon centered nucleophiles, radicals, and heteroatom nucleophiles. In this chapter, an overview of the progress in the field is presented, including a short summary of pioneering works, followed by a more in-depth description of recent results.

Stereoselective synthesis of alkyl-, aryl-, vinyl- and alkynyl-substituted Z-enamides and enol ethers

“…Heteroatom substituted alkenyliodonium salts were reported only in the case of derivatives bearing less electron-rich fluorides and sulphonates substituents. 14 Cyclic hypervalent iodine reagents, especially benziodoxoles, display enhanced stability. 15 In 2016, Yoshikai and coworkers reported the palladium-catalyzed addition of carboxylates onto EthynylBenziodoXole (EBX) reagents to give the corresponding oxygen-substituted VinylBenziodoXoles (VBX), and used the latter in cross-coupling reactions.…”

“Doubly Orthogonal” Labeling of Peptides and Proteins

“…[46][47][48][49][50][51][52][53] In 2018, Gaunt, Suero, and co-workers reported an elegant methionine functionalization using a hypervalent iodine reagent. 53 Our group previously achieved a highly efficient and chemoselective alkynylation of thiols by using hypervalent iodine-based ethynylbenziodoxolone [54][55][56][57][58][59][60] (EBX) reagents (1) in organic solvents, which was also successful for amino acids and dipeptides (Scheme 2A1). 61,62 In collaboration with the Adibekian group, we successfully applied JW-RF-010 (1a), an azide-bearing EBX, in the labeling of native cysteines in vitro and in vivo to afford alkynes as major products (Scheme 2A2).…”

“…State of the Art and Challenges in Cysteine Functionalization can be applied to all cysteine-and other thiol-bearing compounds, including modified ubiquitin and histone proteins. The peptide-and protein-bound vinyl benziodoxolone reagents are stable, yet their inherent reactivity 59,[64][65][66] opens the door for bioconjugations orthogonal to natural functional groups existing in biomolecules. As a proof of concept, we report a palladium-catalyzed Suzuki-Miyaura cross-coupling reaction [67][68][69][70][71] selective at the vinyl hypervalent iodine bond (Scheme 2B).…”

One-Pot Synthesis of 1-[(Triisopropylsilyl)ethynyl]-1,2-benziodoxol-3(1H)-one (TIPS-EBX): Process Safety Assessment and Impact of Impurities on Product Stability

“…Whereas having reactive bonds is a unique advantage to promote synthetic transformations under mild conditions, these reagents need to be manipulated with care to avoid exothermic decomposition or even explosion. In this respect, cyclic hypervalent iodine reagents are interesting, due to their enhanced stability. , Our group in particular demonstrated the exceptional properties of ethynyl­benziodoxolone (EBX) reagents, first discovered by Ochiai and Zhdankin, , for the alkynylation of nucleophiles . Currently, these reagents are used broadly for the introduction of alkynes in direct or transition-metal-catalyzed reactions, as well as in radical-based processes.…”