Structure and Reactivity of N-Heterocyclic Alkynyl Hypervalent Iodine Reagents.

Ethynylbenziodoxol(on)e (EBX) cyclic hypervalent iodine reagents have become popular reagents for the alkynylation of radicals and nucleophiles, but only offer limited possibilities for further structure and reactivity fine-tuning. Herein, the synthesis of new N-heterocyclic hypervalent iodine reagents with increased structural flexibility based on amide, amidine and sulfoximine scaffolds is reported. Solid-state structures of the reagents are reported and the analysis of the I-Calkyne bond lengths allowed assessing the trans-effect of the different substituents. Molecular electrostatic potential (MEP) maps of the reagents, derived from DFT computations, revealed less pronounced σ-hole regions for sulfonamide-based compounds. Most reagents reacted well in the alkynylation of ß-ketoesters. The alkynylation of thiols afforded more variable yields, with compounds with a stronger σ-hole reacting better. In metal-mediated transformations, the N-heterocyclic hypervalent iodine reagents gave inferior results when compared to the O-based EBX reagents.

Recent progress in alkynylation with hypervalent iodine reagents.

Although alkynes are one of the smallest functional groups, they are among the most versatile building blocks for organic chemistry, with applications ranging from biochemistry to material sciences. Alkynylation reactions have traditionally relied on the use of acetylenes as nucleophiles. The discovery and development of ethynyl hypervalent iodine reagents have allowed to greatly expand the transfer of alkynes as electrophilic synthons. In this feature article the progress in the field since 2018 will be presented. After a short introduction on alkynylation reactions and hypervalent iodine reagents, the developments in the synthesis of alkynyl hypervalent iodine reagents will be discussed. Their recent use in base-mediated and transition-metal catalyzed alkynylations will be described. Progress in radical-based alkynylations and atom-economical transformations will then be presented.

Synthesis of polycyclic aminal heterocycles via decarboxylative cyclisation of dipeptide derivatives.

An oxidative-decarboxylative intramolecular cyclisation of dipeptide derivatives is reported. This transformation is promoted by phenyl iodine(III) diacetate (PIDA) in combination with BF3·OEt2. The reaction gives access to a variety of valuable polycyclic N-heterocyclic scaffolds containing 5-, 6-, or 7-membered rings.

Copper-Catalyzed Alkynylation of Hydrazides: An Easy Access to Functionalized Azadipeptides.

We report a copper-catalyzed alkynylation of azadipeptides using ethynylbenziodoxolone (EBX) reagents. Nonsymmetrical ynehydrazides could be obtained in 25-97% yield using azaglycine derivatives as nucleophiles. The transformation is compatible with most functional groups naturally occurring on amino acid side chains and allows the transfer of silyl-, alkyl-, and aryl-substituted alkynes. The obtained α-alkynyl azaglycine products could be further functionalized by nucleophilic attack or cycloaddition on the triple bond.

Small peptide diversification through photoredox-catalyzed oxidative C-terminal modification.

A photoredox-catalyzed oxidative decarboxylative coupling of small peptides is reported, giving access to a variety of N,O-acetals. They were used as intermediates for the addition of phenols and indoles, leading to novel peptide scaffolds and bioconjugates. Amino acids with nucleophilic side chains, such as serine, threonine, tyrosine and tryptophan, could also be used as partners to access tri- and tetrapeptide derivatives with non-natural cross-linking.

Triazene-Activated Donor-Acceptor Cyclopropanes: Ring-Opening and (3 + 2) Annulation Reactions.

Donor-acceptor cyclopropanes substituted with 3,3-dialkyltriazenyl groups are described herein. The strong electron-donating character of the triazene renders the cyclopropanes highly reactive, allowing for catalyst-free ring-opening reactions with methanol and tetracyanoethylene under mild conditions. The triazene-substituted cyclopropanes could also be used as substrates in Lewis acid catalyzed (3 + 2) annulations with silyl enol ethers.