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

Abstract

A benzothiophene S‐oxide catalyst, generated in situ by sulfur oxidation with H2O2, mediates the oxidative coupling of 2‐naphthols. Key to the catalytic process is the capture and inversion of reactivity of a 2‐naphthol partner, using an interrupted Pummerer reaction of an unusual benzothiophene S‐oxide, followed by subsequent coupling with a second partner. The new catalytic manifold has been showcased in the synthesis of the bioactive natural products, (±)‐nigerone and (±)‐isonigerone. Although Pummerer reactions are used widely, their application in catalysis is rare, and our approach represents a new catalytic manifold for metal‐free C−C bond formation.

Metal-free photoredox-catalysed formal C–H/C–H coupling of arenes enabled by interrupted Pummerer activation

“…The high chemoselectivity observed in the reduction of the Ar-DBT + group is particularly noteworthy, given that PTH has previously been shown to catalyse the reduction of aryl halides [45][46][47][48] and trifluoromethyl groups. 49 The process' tolerance of halide and triflyl functional groups signals its orthogonality with regard to traditional crosscoupling and ensures that further structural modification of products can be carried out using conventional cross- While thiophene substrates showed some compatibility (31)(32)(33), furan and pyrrole were too reactive (34,35). We next evaluated the scope with respect to the trapping (hetero)arene.…”

Synthesis of γ-substituted carbonyl compounds from DMSO-mediated oxidation of enynamides: mechanistic insights and carbon- and hetero-functionalizations

“…1). 15 From the Eyring equation, the activation parameters were determined to be Δ H ‡ = 83.5 kJ mol –1 and Δ S ‡ = –37.6 J K –1 mol –1 . The large negative entropy of activation is consistent with an associative transition state, such as TS 19–22 24.…”

“…In this context, dimethyl sulfoxide (DMSO) is advantageous in that the byproduct (Me 2 S) is easily removable (bp = 37 °C) and not so basic (p K a = –5.4 in water) 12–14. Initially, we were concerned that the nucleophiles may attack the O -dienoxysulfenium intermediate 6 (Scheme 1c) at the S -atom (S N 2) rather than at C4 (S N 2′′) as in interrupted Pummerer reactions 15. Notwithstanding, a selective oxygenative coupling at the remote position was obtained and the usefulness of this oxidation is further demonstrated by the introduction of exceptionally diverse nucleophiles, ranging from carbon (indoles, furans, and silyl enol ethers) to heteroatom donors (aliphatic alcohols, thiols, and hydrazides) with good to excellent remote regioselectivity.…”

gem‐Dichlorocyclopropanation of Dicarbonyl Derivatives

“…This hydroxylated naphthyl moiety has potential application in several transformations. [18][19][20] Moreover,achemoselective ketone reduction of final product 2a lead to product 5 as as ingle diastereomer (diastereomeric ratio (d.r.) > 19:1).…”

“…We also demonstrated that in the presence of aluminum chloride compound 2 a could be converted into derivative 4 (48 % yield) in a single step, through a Friedel–Crafts/cyclopropane ring‐opening/aromatization cascade reaction. This hydroxylated naphthyl moiety has potential application in several transformations . Moreover, a chemoselective ketone reduction of final product 2 a lead to product 5 as a single diastereomer (diastereomeric ratio (d.r.…”