o-Silylaryl Triflates: A Journey of Kobayashi Aryne Precursors

Abstract

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.

Cycloaddition Cascades of Strained Alkynes and Oxadiazinones

“…Strained cyclic alkynes and arynes were once avoided in organic synthesis because of their high reactivity and fleeting nature [1] . However, over the past two decades in particular, experimental and computational studies have expanded the utility of cyclic alkynes and arynes, while also enabling studies pertaining to reactivity and selectivity [2–4] . Notably, the use of Kobayashi silyl triflate precursors [2] to access these strained intermediates has paved the way for many synthetic advances.…”

“…However, over the past two decades in particular, experimental and computational studies have expanded the utility of cyclic alkynes and arynes, while also enabling studies pertaining to reactivity and selectivity [2–4] . Notably, the use of Kobayashi silyl triflate precursors [2] to access these strained intermediates has paved the way for many synthetic advances. As such, strained cyclic alkynes and arynes have been employed in the synthesis of natural products, [5a] medicinally privileged scaffolds, [5b] ligands, [5c,d] agrochemicals, and organic materials [5e] …”

The Aryne Phosphate Reaction

“…[5] Consequently, arynes are captured efficiently by arynophiles in diverse reactions, like nucleophilic additions, pericyclic reactions, insertions or multicomponent processes. [6] Due to this broad applicability, aryne-based transformations are a powerful toolbox in chemical synthesis, underlined by their use in complex synthetic sequences towards natural products. [7,8] Figure 1.…”

“…[18] Biju and He demonstrated later in 2014 and 2016 how this reactivity can be applied in multicomponent reactions with carbonyls or CO2. [19,20] Furthermore, Studer, Daugulis, and Miura developed aryne induced σ-P III -X bond insertions accessing ortho-stannylated, silylated or phosphinylated arylphosphines (6). [21][22][23] Analogously, Alajarin and Gogoi presented π-P V =X bond insertions leading to ortho-aminated, thiolated or hydroxylated arylphosphonium products (8).…”

“…However, no exclusive aryne-based Oarylation has ever been described in the synthesis of organophosphorous compounds. More generally, "there are limited examples of O-arylation transformations" [6] using arynes (scheme 1, B), overall restricted to few hydroxyl and carboxylgroup arylation protocols since 2004. [30][31][32] Despite the many studies scrutinizing the reactivity of diverse arynophiles, the ability of phosphates to engage in reactions with arynes is absent from the literature.…”