Current Organic Chemistry - Volume 24, Issue 18, 2020

This Special Issue covers the hot topics on recent synthetic interest in halogen and related chemistry as well as the unique characteristics of halogen compounds. The excellent reviews by the experts and eminent researchers engaged in the recent advances, i.e., preparations, reactions, and mechanistic studies of unique organohalogen compounds, halogen bond interaction as the catalysis, and halogen-controlled unique reactions for synthesizing useful organic molecules, such as pharmaceutical compounds and organic materials, are provided in this Special Issue.

Hypervalent iodine compounds have proved to be very useful reagents to bring about various oxidative transformations including (i) α-functionalization of carbonyl compounds, (ii) oxidation of phenols, and (iii) oxidative rearrangement of ketones and α,β- unsaturated ketones. These reactions find interesting applications in the development of newer and convenient approaches for the synthesis of flavonoids. This review focuses on the use of most common three hypervalent compounds, namely iodobenzene diacetate, [hydroxy(tosyloxy)iodo]benzene, and [bis-trifluoroacetoxy(iodo)]benzene in the synthesis of cis/trans-3-hydroxyflavanones, 3-hydroxyflavones (flavonols), flavones, isoflavones and related compounds.

Since oxazoles have found widespread applications not only as synthetic intermediates but also as biologically active compounds, much effort has been focused on developing novel and efficient methods for the synthesis of this heterocycle. From the viewpoint of green and sustainable chemistry, hypervalent iodine and other halogen reagents have gained increasing popularity in metal-free oxidative transformation due to their low toxicity, transition-metal-like reactivity, high stability, easy handling and other benefits. In this account, our two approaches to the metal-free synthesis of oxazoles by means of a peculiar activation of alkynes by iodine species are described with the related contexts. One is iodine(III)-mediated/catalyzed oxidative cycloisomerization reactions of N-propargyl amides for the preparation of oxazoles bearing various functional groups at their side chains. In these reactions, iodine(III) species works as a donor of various heteroatomic functional groups as well as an activator of carbon-carbon triple bonds in a single step. Furthermore, this methodology can be extended to iodine(III)-mediated/catalyzed oxidative annulation of alkynes and nitriles as another approach, in which heteroatoms on iodine(III) species are incorporated in the azole rings.

Due to similar reactivity in comparison with aromatic organometallic reagents, diaryliodonium salts are currently in broad usage as less toxic, highly efficient, stable and mild electrophilic reagents in organic synthesis. The hypervalent iodine center of diaryliodonium salts can lead to unique reactivity, which thus is frequently presented in metal-free arylations or metal-involved elementary reactions such as oxidative addition, reduction elimination, ligand coupling and ligand exchange reaction. As such, diaryliodonium salts have experienced explosive growth by transferring aromatics to the target molecules. In contrast to the reviews on the synthetic utility or aryl transformations by using diaryliodonium salts, this review provides a summary of their structures and the synthetic strategies towards them during recent decades.

Hypervalent iodine-promoted dearomatization of phenols has received intense attention. This mini-review summarizes recent computational mechanistic studies of phenolic dearomatizations promoted by hypervalent iodine(III) reagents or catalysts. The first part of this review describes mechanisms of racemic dearomatization of phenols, paying special attention to the associative and dissociative pathways. The second part focuses on mechanisms and selectivities of diastereo- or enantio-selective dearomatization of phenols.

Halogen bond interactions, which take place between an electrophilic halogen and the electron-pair of a Lewis base and exhibit high directionality (approximately 180°), are non-covalent bond interactions similar to the hydrogen bond interaction. Many reports on halogen bond interactions have been published thus far, but many of them discuss halogen bond in the context of crystal engineering of supramolecular architecture. Since a seminal report by Bolm in 2008, halogen bond-assisted or -promoted organic synthesis has received significant attention. This review aims to introduce the molecular design of suitable halogen bond donors and organic transformations involving halogen bond interactions to afford a variety of organic compounds.

Iodine is an element that exhibits characteristic features of heavy halogen, and several compounds containing iodine constitute important synthetic intermediates due to synthetically easy manipulation. To utilize iodine units for organic synthesis, a highly regio- and stereoselective introduction of iodine to versatile building blocks is significant, and a lot of research works for the selective introduction of iodine to alkynes or alkenes have been conducted. In this review article, we describe regio- and stereoselective hydroiodination to multiple bonds of building blocks, and its synthetic applications as key intermediates to construct several important compounds in organic chemistry.

β-Lactams, found in β -lactam antibiotics, are the structurally distorted cyclic compounds being subjected to nucleophilic acyl substitution reaction. α-Fluorination of β -lactams is a simple and expedient approach to control the reactivity of β-lactam ring toward nucleophilic attack, which would hopefully lead to the new design of future antibiotics. From the viewpoint of obtaining multisubstituted α -fluoro-β-lactams, α -bromo-α- fluoro-β-lactams are considered as key compounds for structure functionalization, including nucleophilic substitution reaction, aldol-type reaction and metal-catalyzed crosscoupling reaction. All the reactions can be conducted smoothly to afford a variety of multisubstituted α-fluoro-β-lactams. During the course of the examination, chiral α,α-difluoro- β-lactams and α -bromo-β-fluoro-α-lactams are successfully obtained, which are considered potent precursors for making stereocontrolled multisubstituted α-fluoro-β-lactams.

The development of an efficient and mild synthetic methodology for the construction of bioactive fluorine-containing molecules represents one of the hot research topics in general synthetic organic chemistry. In this review, some recent progresses achieved in the development of detrifluoroacetylatively generated mono-fluorinated enolates via CC bond cleavage and their asymmetric nucleophilic reactions for assembly of chiral quaternary C-F center containing compounds.