Organosulfur compounds have long played a vital role in organic chemistry and in the development of novel chemical structures and architectures. Prominent among these organosulfur compounds are those involving a sulfur(IV) center, which have been the subject of countless investigations over more than a hundred years. In addition to a long list of textbook sulfur-based reactions, there has been a sustained interest in the chemistry of organosulfur(IV) compounds in recent years. Of particular interest within organosulfur chemistry is the ease with which the synthetic chemist can effect a wide range of transformations through either bond formation or bond cleavage at sulfur. This review aims to cover the developments of the past decade in the chemistry of organic sulfur(IV) molecules and provide insight into both the wide range of reactions which critically rely on this versatile element and the diverse scaffolds that can thereby be synthesized.

Bond-Forming and -Breaking Reactions at Sulfur(IV): Sulfoxides, Sulfonium Salts, Sulfur Ylides, and Sulfinate Salts.

The synthesis of biaryls from benzyne intermediates offers an alternative strategy to conventional metal-catalyzed cross-coupling approaches. The concept is as old as benzyne itself, being the basis of Wittig's seminal observations on biphenyl synthesis from phenyl lithium and fluorobenzene in 1940. In the intervening 75 years, the transformation has grown to encompass a remarkable scope of reaction classes, and continues to develop as new benzyne precursors enable inventive biaryl syntheses under mild conditions. This review will cover all aryne methods relevant to biaryl synthesis, drawing together key ideas from the older literature involving halobenzene precursors, with a more comprehensive coverage of modern methods using 2-(trimethylsilyl)phenyl triflates and tri-ynes as the source of benzyne. Collectively, we hope to highlight the power of aryne chemistry to access a huge range of biaryl structures from a versatile and highly customizable set of substrates.

Synthesis of biaryls using aryne intermediates

The total syntheses of polycyclic natural products by exploiting an aryne as the key reactive species are reviewed. A short introduction summarizes the basic reactivities of aryne species as well as the methods for its generation. In the main part, early examples and the recent reports (mainly 2012–present) on the use of arynes in multistep syntheses are described.

Aryne-based strategy in the total synthesis of naturally occurring polycyclic compounds.

Arynes and donor-acceptor (D-A) cyclopropanes are two classes of strained systems having the potential for numerous applications in organic synthesis. The last two decades have witnessed a renaissance of interest in the chemistry of these species primarily because of the mild and robust methods for their generation or activation. Commonly, arynes as easily polarizable systems result in 1,2-disubstitution, whereas D-A cyclopropanes as polarized systems lead to 1,3-bisfunctionalization thereby showing striking similarities. Transformations with 1,2- and 1,3-dipoles afford cyclic structures. With arynes, emerging four-membered rings as intermediates might react further, whereas the analogous five-membered rings obtained from D-A cyclopropanes are most often the final products. However, there are a few cases where these intermediates behave surprisingly differently. This Minireview highlights the parallels in reactivity between arynes and D-A cyclopropanes thereby shedding light on the neglected similarities of these two reactive species.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.201909213

Uncovering the Neglected Similarities of Arynes and Donor-Acceptor Cyclopropanes.

Recent developments in aryne chemistry are reviewed with a particular focus on synthetic methods. This includes an overview of the precursors of arynes and their activators; the generation of aryne...

The Renaissance and Bright Future of Synthetic Aryne Chemistry

One of the most distinct characters of aryne chemistry over other synthetic methodologies is its ability to simultaneously functionalize the vicinal two positions of a benzene ring with diverse combinations of substituents. Moreover, the functionalization of the remaining four positions can be also achieved through multiaryne equivalents, in which more than one triple bond is generated on the different locations of the same benzene ring. This tutorial review summarizes the applications of benzdiyne and benztriyne equivalents from the standpoint of synthetic organic chemistry as well as in the preparation of polycyclic aromatic functional frameworks.

Aryne multifunctionalization with benzdiyne and benztriyne equivalents

Arynes are among the most active organic intermediates and have found numerous applications in expeditious preparation of substituted arenes. In the past 20 years, chemists have witnessed a resurgence in aryne chemistry, which is mainly attributed by the extensive utilization of Kobayashi's method, a fluoride-induced removal of the TMS group with concomitant departure of its ortho OTf group on o-silylaryl triflates. Nowadays, o-silylaryl triflates are the most frequently employed aryne precursors. This review provides an overview of the history of Kobayashi's method, its methodological achievements, and its applications in the synthesis of natural products, bioactive molecules, and polycyclic aromatic hydrocarbons.

o-Silylaryl Triflates: A Journey of Kobayashi Aryne Precursors.

An aryne precursor with a potential to perform domino aryne chemistry was proposed and synthesized. The reaction of this reagent with benzothioamide derivatives could afford 2,4-disubstituted benzothiazole with sequential incorporation of C–S, C–N, and C–C bonds on the consecutive three positions of the aryne precursor.

Domino Aryne Precursor: Efficient Construction of 2,4-Disubstituted Benzothiazoles

An aryne 1,2,3-trisubstitution with aryl allyl sulfoxides is accomplished, featuring an incorporation of C–S, C–O, and C–C bonds on the consecutive positions of a benzene ring. The reaction condition is mild with broad substrate scope. Preliminary mechanistic study suggests a cascade formal [2 + 2] reaction of aryne with S═O bond, an allyl S → O migration, and a Claisen rearrangement.

Aryne 1,2,3-Trifunctionalization with Aryl Allyl Sulfoxides

1,2-Benzdiyne equivalents possess the unique property that they can react with two arynophiles through iteratively generated 1,2- and 2,3-aryne intermediates. Upon rational modification on the second leaving group of these aryne precursors, a domino aryne annulation approach was developed through a nucleophilic–ene reaction sequence. Various benzo-fused N-heterocyclic frameworks were achievable under transition metal-free conditions with a broad substrate scope.

Jiarong Shi

Papers

Aryne multifunctionalization with benzdiyne and benztriyne equivalents

o-Silylaryl Triflates: A Journey of Kobayashi Aryne Precursors.

Domino Aryne Precursor: Efficient Construction of 2,4-Disubstituted Benzothiazoles

Aryne 1,2,3-Trifunctionalization with Aryl Allyl Sulfoxides

Domino Aryne Annulation via a Nucleophilic-Ene Process.