Aryne Insertion into σ Bonds

Abstract

The synthesis of aryne intermediates from ortho‐(trimethylsilyl)aryl triflates by employing a fluoride source, first reported by Kobayashi′s group, has provided a new avenue for the simultaneous construction of two sigma bonds on a benzene ring by inserting an aryne into the sigma bond in a more‐convenient manner. The generation of ortho‐substituted benzenes through aryne intermediates offers a potent scaffold for the synthesis of bioactive heterocyclic compounds, ligands, and natural products. The main aim of this Focus Review is to highlight the application of Kobayashi′s aryne precursor to the one‐pot synthesis of ortho‐substituted benzenes. Examples include transformations that employ transition‐metal catalysis and those that do not.

Transition-Metal-Free Thioamination of Arynes Using Sulfenamides

“…In view of our interest in the transition-metal-free aryne reactions, , we envisioned that the cleavage of the S–N σ-bonds in sulfenamides and stitching the two fragments at the C–C triple bond of arynes could result in straightforward access to o -sulfanylanilines . The synthesis of o -sulfanylaniline using aryne as the aryl source was demonstrated by Larock in 2005 via the insertion of arynes into the S–N bond of trifluoromethanesulfenamides (Scheme , eq 1). , Notably, the presence of a CF 3 group on sulfinamide was necessary for the reaction, which increases the N–H acidity and also the electrophilicity of the sulfinyl moiety. Later in 2015, Greaney and co-workers uncovered the aryne three-component coupling triggered by thiols and O -benzoyl N,N -dialkylhydroxylamines as the third component for the construction of o -sulfanylanilines (eq 2) .…”

C4–H indole functionalisation: precedent and prospects

“…Arynes generated from fluoride-activated precursors admit a wide variety of carbon- and/or heteroatom-based groups, generally under mild conditions and with controlled regioselectivity. 26 4,5-Indolyne undergoes nucleophilic attack preferentially at its more linear carbon, C5. 27 However, this can be overturned by using substituent effects.…”

Reactions of Sulfoxides with Benzynes

“…4 This unique property allows benzynes to react with sulfoxides for the synthesis of substituted benzenes. 5 6 In 1966, the Day group serendipitously discovered that dimethyl sulfoxide (DMSO) reacts with arynes generated from aryl halides to produce 2-(methylsulfanyl)phenol derivatives (Scheme 2a ). 6a Similar transformations were subsequently reported by several other groups, 6` c d e but in the early era of benzyne chemistry, the harsh conditions required to generate benzynes from halobenzenes resulted in low reaction yields with DMSO, thereby limiting their further application.…”