Enantioselective Brønsted base catalyzed [4+2] cycloaddition

[Name of the Instotution]

Enantioselective Brønsted base catalyzed [4+2] cycloaddition

1. Introduction

This proposal will be concerned with the syntheses of 1,8,9,16-tetrahydroxytetraphenylene derivatives and their applications as Brønsted base organocatalysts for [4+2] cycloaddition between anthrone and maleimides. The structural modifications of the catalysts and their related catalytic properties are described and discussed in details.

Since its discovery in 1926, Diels-Alder reaction is regarded as one of the most important and fascinating transformations in organic synthesis.1, (a) and (b) It has been extensively used as one of the most versatile synthetic tools in the construction of a large number of important building blocks. Many past efforts have shown that chiral metal complexes are efficient catalysts in asymmetric Diels-Alder reaction. Years ago, Corey reviewed the art of enantioselective metal-catalyzed Diels-Alder reaction, which had been developed by his group.1 In contrast, asymmetric Diels-Alder reaction catalyzed by organocatalysts has only a rather short history and has been neglected for quite a long time.

After the first example was reported by Kagan in 1989,2 there was limited examples for Brønsted base-catalyzed Diels-Alder reactions.3, 4 and 5 More recently, Tan reported a highly enantioselective and diastereoselective Diels-Alder reaction between anthrones and maleimides using modified guanidines.6 Deng also reported a highly enantioselective and diastereoselective Diels-Alder reaction with pyrones using modified cinchona alkaloids as an acid-base bifunctional catalyst.

Tetraphenylene (tetrabenzo[a,c,e,g]cyclooctatetraene) (1) is a structurally exceptional molecule featuring a rigid conformation (Scheme 1).  It consists of four benzene rings, which are arranged alternatively above and below the mean plane of the molecule. The molecule then belongs to a D2dsymmetry point group. 9 and 10 Due to the high inversion barrier of the central cyclooctatetraene,11 a chiral version of tetraphenylenes can be obtained by introducing substituents appropriately. A program has then been initiated in our laboratories in the syntheses of building blocks 2,3, 4, 5, and 6. Noteworthy is that 2-4 are chiral, while 5 and 6 are achiral. Geometrically, 3 is a linear unit containing reactive sites, pointing toward opposite directions.

In this proposal, we would like to report the syntheses of thirteen amino-alcohols derived from tetraphenylenol 3and their catalytic efficiencies by employing them as organocatalysts in [4+2] cycloaddition reactions.

2. Methodology

All reagents and solvents were reagent grade. Further purification and drying following the guidelines of Perrin and Armarego were used when necessary.17 Organic solvents were concentrated under reduced pressure on a rotary evaporator. Chromatographic purification of products was performed on Macherey Nagel Kieselgel 60 M (230-400 mesh). Thin-layer chromatography (TLC) was performed on E. Merck silica gel 60 F254 (0.25 mm thickness) coated on aluminum plates. Visualization of the developed chromatogram was performed by a spray of 5% w/v dodecamolybdophosphoric acid in ethanol and subsequent heating. Melting points were measured with a Reichert apparatus in Celsius degrees and are uncorrected. Optical rotations were obtained with a Perkin-Elmer model 341 polarimeter, operating at 589 nm. Nuclear magnetic resonance (NMR) spectra were recorded with a Bruker DPX300 NMR spectrometer at 300 MHz (1H) or at 75 MHz (13C) or a Bruker ADVANCE-III NMR spectrometer at 400 MHz (1H) or at 100 MHz (13C). All NMR measurements were carried out at room temperature in ...