Thiourea-catalyzed Diels–Alder reaction of a naphthoquinone monoketal dienophile

Carsten S Kramer,Stefan Bräse

doi:10.3762/bjoc.9.158

Abstract

A variety of organocatalysts were screened for the catalysis of the naphthoquinone monoketal Diels–Alder reaction. In this study we found that Schreiner's thiourea catalyst 10 and Jacobson's thiourea catalyst 12 facilitate the cycloaddition of the sterically hindered naphthoquinone monoketal dienophile 3 with diene 4. The use of thiourea catalysis allowed for the first time the highly selective synthesis of the exo-product 2a in up to 63% yield. In this reaction a new quaternary center was built. The so formed cycloaddition product 2a represents the ABC tricycle of beticolin 0 (1) and is also a valuable model substrate for the total synthesis of related natural products.

Highlights

In the past few years, many different types of organocatalysts were found to accelerate a variety of reactions
In our recent studies towards a synthetic access to the natural product beticolin 0 (1) [9] (Scheme 1), we have found that naphthoquinone monoketals are suitable building blocks for our designed synthesis [9]
Jacobsen's thioureas [13] (Table 2, entry 7) and [14] (Table 2, entry 8) were tested whereby the 3,5bis(trifluoromethyl)phenyl-substituted thiourea 12 was superior to catalyst 11

Summary

Introduction

In the past few years, many different types of organocatalysts were found to accelerate a variety of reactions. Due to the value of the Diels–Alder reaction for the synthetic community, different organocatalysts have been developed to catalyze this atom-economical cycloaddition in a highly enantioselective fashion. In our recent studies towards a synthetic access to the natural product beticolin 0 (1) [9] (Scheme 1), we have found that naphthoquinone monoketals are suitable building blocks for our designed synthesis [9]. The naphthoquinone monoketal dienophile 3 was found to undergo cycloaddition with diene 4 to tricycle 2, which represents the ABC-ring system of beticolin 0 (1) and other beticolins [10]

Results

Discussion

Conclusion