Enantioselective aza-Friedel-Crafts reaction of furan with α-ketimino esters induced by a conjugated double hydrogen bond network of chiral bis(phosphoric acid) catalysts.

Manabu Hatano,Haruka Okamoto,Kohei Toh,Taro Kawakami,Akira Sakakura,Hidefumi Nakatsuji,Kazuaki Ishihara

doi:10.1039/c8sc02290a

Abstract

Chiral C 2- and C 1-symmetric BINOL-derived bis(phosphoric acid) catalysts, which have OP([double bond, length as m-dash]O)(OH)2/OP([double bond, length as m-dash]O)(OH)(OR) moieties at the 2,2'-positions, were developed and used for the enantioselective aza-Friedel-Crafts reaction of 2-methoxyfuran with α-ketimino esters for the first time. The intramolecular conjugated double hydrogen bond network is a key to increasing the Brønsted acidity and preventing deactivation of the catalysts. Highly functionalized α-amino acid derivatives with a chiral quaternary carbon center could be transformed into versatile optically active N- and O-heterocycles and an α-aryl-substituted serine.

Highlights

According to the general classi cation of combined acid catalysts described by Yamamoto,[3] some chiral Brønsted acid catalysts R*(XH)[2] with a hydrogen bond network could be considered part of a Brønsted acid-assisted Brønsted acid (BBA) catalyst system
Since 2003, when Rawal reported the rst example of an intramolecular single hydrogen bonding network in chiral TADDOLs (a,a,a0,a0-tetraaryl-1,3-dioxolan-4,5-dimethanols)4a,c for the enantioselective hetero-Diels–Alder reaction, and a er Schaus developed chiral 3,30-diaryl-BINOLs (1,10-bi-2-naphthol)4b for the enantioselective Morita–Baylis–Hillman reaction, great effort has been devoted to this research area (Fig. 1a)
We envisioned that an intramolecular double hydrogen bond network may represent a new strategy for the design of chiral Brønsted acid catalysts

Summary

Introduction

The hydrogen bond network of chiral multiprotic acid catalysts plays an important role in activating Brønsted acidity, controlling conformational exibility, and producing high enantioselectivity.[1,2] According to the general classi cation of combined acid catalysts described by Yamamoto,[3] some chiral Brønsted acid catalysts R*(XH)[2] with a hydrogen bond network could be considered part of a Brønsted acid-assisted Brønsted acid (BBA) catalyst system. Catalysts might have an intramolecular single hydrogen bond network with the use of bis(monoprotic acid)s R*(XH)[2]. We envisioned that an intramolecular double hydrogen bond network may represent a new strategy for the design of chiral Brønsted acid catalysts.

Results

Conclusion