Cascades of Interrupted Pummerer Reaction‐Sigmatropic Rearrangement

Abstract

A new class of Pummerer chemistry has emerged as a powerful tool in organic synthesis. The new technology consists of a beautiful cascade of an interrupted Pummerer reaction and the subsequent [3,3] sigmatropic rearrangement. The interrupted Pummerer reactions of alkenyl or aryl sulfoxides with unsaturated nucleophiles such as allylic silanes, ketones, and phenols provide sulfonium intermediates, which are ready to undergo smooth charge-accelerated [3,3] sigmatropic rearrangement with excellent to exclusive regioselectivity. Some of the transformations proceed with transient loss of aromaticity. The reactions afforded five-membered heterocycles, benzofurans, and biaryls of importance, depending on the sulfoxides and nucleophiles used. The reactions are unique and game-changing because they are efficient, robust, redox-neutral, regioselective, and metal-free, which perfectly fits the need of modern organic synthesis. This chemistry also underscores the synthetic potential of organosulfur chemistry.

Sigmatropic Dearomatization/Defluorination Strategy for C−F Transformation: Synthesis of Fluorinated Benzofurans from Polyfluorophenols

“…A positive charge at the sulfur center facilitates sigmatropic rearrangement, C−C bond formation thus being executed under mild conditions, generally at room temperature or below. As a variation of these transformations, we also developed the synthesis of benzofurans from ketene dithioacetal monoxides (KDM) and phenols ,…”

The Interrupted Pummerer Reaction in a Sulfoxide‐Catalyzed Oxidative Coupling of 2‐Naphthols

“…For example, selective oxidation and electrophilic activation of sulfur must be possible in the presence of other nucleophiles, and interrupted Pummerer reactivity must out‐run side reactions (e.g. classical Pummerer chemistry) and rearrangements of sulfonium intermediates A and B ,–…”

“…Adding the oxidant and activator in portions greatly improved reaction efficiencya nd product 2a was isolated in 84 %y ield (entry 2). Control experiments revealed that 3a' ', TFA, and TFAA were all essential for the reaction to proceed (entries [3][4][5]. Other terminal oxidants (e.g.…”

“…Such couplings are typically achieved using stoichiometric metals,o rm etal catalysts, [2] however,m etal-free processes that do not rely on expensive metal catalysts,a nd do not generate metallic waste,are desirable. [3,4] TheP ummerer reaction, [5] including its so-called interrupted variant, [6] involves the activation of sulfoxides and the subsequent transformation of the resultant sulfonium salts.As tools for synthesis,t he family of Pummerer processes continues to find widespread application en route to important targets,i ncluding natural products,b ioactive molecules and advanced materials. [5] It is therefore surprising that the use of Pummerer reactions to drive catalysis is rare, [7] and the use of sulfoxides to catalyze carbon-carbon bond formation via Pummerer processes has not been described.…”

“…[3,4] TheP ummerer reaction, [5] including its so-called interrupted variant, [6] involves the activation of sulfoxides and the subsequent transformation of the resultant sulfonium salts.As tools for synthesis,t he family of Pummerer processes continues to find widespread application en route to important targets,i ncluding natural products,b ioactive molecules and advanced materials. [5] It is therefore surprising that the use of Pummerer reactions to drive catalysis is rare, [7] and the use of sulfoxides to catalyze carbon-carbon bond formation via Pummerer processes has not been described. We postulated that sulfoxides could serve as catalysts for oxidative union of two carbon nucleophiles through the operation of an interrupted Pummerer process (Scheme 1A).…”