A Highly Efficient Friedel–Crafts Reaction of 3‐Hydroxyoxindoles and Aromatic Compounds to 3,3‐Diaryl and 3‐Alkyl‐3‐aryloxindoles Catalyzed by Hg(ClO₄)₂⋅3 H₂O

Abstract

We report a highly efficient Friedel-Crafts reaction of 3-alkyl or 3-aryl 3-hydroxyoxindoles with a variety of aromatic and heteroaromatic compounds to unsymmetrical 3,3-diaryloxindoles or 3-alkyl-3-aryloxindoles, which are interesting medicinal targets and useful building blocks for the synthesis of natural products. Hg(ClO(4))(2)·3H(2)O was identified as a powerful catalyst for this reaction, and is significantly more efficient than other screened metal perchlorate hydrates and Brønsted acids such as HOTf and HClO(4). The high catalytic property of Hg(ClO(4))(2)·3H(2)O originates from the unprecedented dual activation effects of aromatic mercuration, which could generate a strong protic acid to facilitate the generation of a carbocation at the C3-position of oxindoles and simultaneously form the more reactive nucleophilic reaction partner.

A Highly Efficient Friedel–Crafts Reaction of Tertiary α‐Hydroxyesters or α‐Hydroxyketones to α‐Quaternary Esters or Ketones

“…Brønsted acids11 such as HClO 4 and TfOH could also catalyze the reaction (Table 1, entries 9 and 10), and, in particular, HClO 4 was as efficient as Hg(ClO 4 ) 2 ⋅3 H 2 O. This result was to some extent unexpected, as Hg(ClO 4 ) 2 ⋅3 H 2 O was found to be much more efficient than HClO 4 in the Friedel–Crafts arylation of 3‐hydroxyoxindoles,9a possibly owing to the aromatic mercuration. In light of this, both catalysts were comparatively evaluated in some typical solvents.…”

“…As part of a program directed at the catalytic construction of tetrasubstituted carbon centers using easily available starting materials and catalysts,8 we were interested in the elaboration of tertiary α‐functionalized alcohols. In this context, we have recently developed the catalytic Friedel–Crafts9a and Ritter reaction9b of 3‐substituted 3‐hydroxyoxindoles, and a tandem reaction towards 3,3‐disubstituted benzofuranones 9c. Based on these results, we further tried catalytic Friedel–Crafts arylation of tertiary α‐hydroxyesters or α‐hydroxyketones.…”

Transition‐metal‐free Chemoselective Oxidative C−C Coupling of the sp3 C−H Bond of Oxindoles with Arenes and Addition to Alkene: Synthesis of 3‐Aryl Oxindoles, and Benzofuro‐ and Indoloindoles

“…In this context, arylation of oxindoles via intermolecular– and intramolecular– C−C coupling using aryl halide partners catalyzed by TM‐catalysts have been well explored (Scheme ). Hg II ‐catalyzed Friedel–Crafts reactions of N ‐protected 3‐substituted 3‐hydroxyoxindoles with electron‐rich N ‐methyl indoles and electron‐rich phenols, Fe III ‐catalyzed cross‐coupling reactions of an excess amount of activated arenes such as anisole and thiophene with 3‐benzyl/phenyl‐substituted oxindoles, and Rh‐catalyzed arylation of imine‐based oxindoles with arylboronic acid have been reported in the literature …”

Metal‐Free Azidation of α‐Hydroxy Esters and α‐Hydroxy Ketones Using Azidotrimethylsilane

“…This is possibly because the electron‐withdrawing effect of the ester group makes it difficult to generate the carbocation intermediates. With our continuation in catalytic functionalization of tertiary alcohols bearing an α‐electron‐withdrawing group, we have developed a Friedel‐Crafts reaction of α‐tertiary hydroxy esters with electron‐rich arenes to furnish α‐quaternary esters and ketones,– along with several S N 1 type substitution reactions of 3‐aryl‐3‐hydroxy oxindoles –. On the basis of these work, we attempt to develop a catalytic azidation of α‐tertiary hydroxy esters and TMSN 3 .…”