Brønsted Acid Catalyzed Oxygenative Bimolecular Friedel–Crafts‐type Coupling of Ynamides

Abstract

A non-metal approach for accessing α-oxo carbene surrogates for a C-C bond-forming bimolecular coupling between ynamides and nucleophilic arenes was developed. This acid-catalyzed coupling features mild temperature, which is critical for the required temporal chemoselectivity among nucleophiles. The scope of nucleophiles includes indoles, pyrroles, anilines, phenols and silyl enolethers. Furthermore, a direct test of S 2' mechanism has been provided by employing chiral N,N'-dioxides which also enlightens the nature of the intermediates in related metal-catalyzed processes.

Keteniminium Ions: Unique and Versatile Reactive Intermediates for Chemical Synthesis

“…An interesting and particularly relevant extension of this reactivity was reported in 2017 by the Shin group, who devised a remarkable oxidative intermolecular Friedel-Crafts-type coupling of electron-rich arenes or silyl enol ethers (Scheme 32). 100 The design of this reaction, which is closely related to the intramolecular version reported by the Maulide group (Scheme 11), 39 is actually based on the trapping of keteniminium bistriflimidate 2 with 2-chloropyridine N-oxide (156)…”

“…106 While efficient, it should however be noted that the exact same transformation yielding 158 can be performed using catalytic amounts of bistriflimide instead of the gold catalyst (Scheme 32). 100 The use of other oxidants such as nitrones 182 also highlights the synthetic usefulness of this method for the generation of α-oxo-carbenoids, the imine 184 released in this case upon generation of carbenoid 166 trapping this reactive intermediate to give, after hydrolysis, α-amino-amides 185. 107 Note, the use of nitrosoarenes in place of the nitrone was also found to be efficient and promoted an efficient oxoimination instead of the oxoamination observed with nitrones.…”

Synthesis of α‐Trifluoromethylthiolated and α‐Thiocyanated Ketones Using Umpoled Enolates

“…However, the polarity of many functional groups may be reversed by use of the Umpolung strategy. In recent years, umpoled enolates systems have been well developed by groups of Szpilman, Maulide, Zhang, Hashmi, Shin and others, which could react with various nucleophiles such as alcohols and thiols to give diverse α‐functionalized ketones (Scheme d). Because the most common and inexpensive CF 3 S sources are nucleophilic species such as AgSCF 3 , we envisioned a new strategy for preparation of α‐trifluoromethylthiolated ketones via reaction of a nucleophilic CF 3 S reagent with a umpoled enolate.…”

Gold‐Catalyzed Oxidative Alkyne Functionalization by N−O/S−O/C−O Bond Oxidants

“…In 2017 Shin and coworkers introduced gold catalyzed oxidative enantioselective oxyarylations at C-3 position of N-methyl indole with internal ynamides where two equivalent of Nakajima's chiral (S)bipyridine-N,N'-dioxide [141] 215 is used as an external oxidant to incorporate chiral center in the final product (Scheme 117). [142] The chirality transfer from the oxidant to the final product is presumed to take place either by protodeauration of oxygenated alkenyl gold intermediate 216 followed by the stereogenic nucleophilic addition through S N 2' manner (path a) or via S N 2' addition on intermediate 216 thereafter nonracemizing protodeauration of C-or O-bounded enolate species 217/218 (path b). The reaction has been performed in DCE and water medium with significant enantioselectivity up to 82% ee.…”