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

Zhen He,Alexander P Pulis,David J Procter

doi:10.1002/anie.201903492

Zhen He, Alexander P Pulis + Show 1 more

Open Access

https://doi.org/10.1002/anie.201903492

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Abstract

A benzothiophene S-oxide catalyst, generated in situ by sulfur oxidation with H2 O2 , 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.

Highlights

This work1 H2O2, TFAA R n catalysis by interrupted Pummerer reaction n application in the total synthesis of nigerone
Carbon-carbon bond formation underpins almost every synthetic undertaking1 and oxidative processes that unite two nucleophilic partners,2 at the expense of a C–H bond in each partner, are at the forefront of synthetic technology
The Pummerer reaction,5 including its so-called interrupted variant,6 involves the activation of sulfoxides and the subsequent transformation of the resultant sulfonium salts

Summary

This work

1 H2O2, TFAA R n catalysis by interrupted Pummerer reaction n application in the total synthesis of nigerone. The Interrupted Pummerer reaction in sulfoxide-catalyzed oxidative couplings. The studies were designed to ascertain whether; (i) 2-naphthols would undergo nucleophilic addition to the activated sulfoxide (cf A) through oxygen or through carbon in an SEAr fashion; (ii) if the reaction occurred through oxygen, would the resultant aryloxysulfonium salts I act as electrophiles and couple with. When 3methyl benzothiophene S-oxide (3a) was employed in CH2Cl2, the desired coupling product 2a was formed in high isolated yield (87%). Adding the oxidant and activator in portions greatly improved reaction efficiency and product 2a was isolated in 84% yield (entry 2). Other terminal oxidants (e.g. UHP and tBuOOH) were less effective (entry 6-7)

Homocouplinga

Cross-couplingh

Mechanistic probe for the formation of intermediate I Me