Gold(I)-Catalyzed Tandem Synthesis of Polycyclic Dihydroquinazolinones

Jingyang Sun,Jae-Sang Ryu,Yoona Song

doi:10.3390/catal11121436

Abstract

A gold-catalyzed cascade process for the synthesis of dihydroquinazolinone scaffolds was developed. A series of gold catalysts were screened for this tandem transformation, and the (PPh3)AuCl/AgOTf catalyst combination was found to be the best catalyst system. This method is characterized by good yields, high regioselectivity, and broad substrate scope. This method is also applicable to the synthesis of tetracyclic dihydroquinazolinones and seven-membered ring-fused dihydroquinazolinones.

Highlights

IntroductionAs bioactive alkaloids [4,5,6], dihydroquinazolinones [7,8,9] are an important class of compounds and substructures of structurally complex polycyclic alkaloids with a wide range of biological activities
To investigate the feasibility of the gold-catalyzed one-pot cascade process for the synthesis of dihydroquinazolinone scaffolds, we initially focused on the double cascade cyclization of alkyne-tethered anthranilamide 1a as a benchmark substrate, which was readily prepared in one step from commercially available isatoic anhydride and 1-amino-4pentyne
The desired dihydroquinazolinone product 2a was obtained in 52% yield along with 6% of ketone byproduct 3a (Table 1, entry 1), which presumably was formed from the goldcatalyzed addition of H2 O to the alkyne moiety of 1a

Summary

Introduction

As bioactive alkaloids [4,5,6], dihydroquinazolinones [7,8,9] are an important class of compounds and substructures of structurally complex polycyclic alkaloids with a wide range of biological activities. Attention due to their unique structural features and promising bioactivities, which have prompted the research on synthetic dihydroquinazolinones with pharmacological potential (Figure 1). Various synthetic approaches to bicyclic dihydroquinazolinone scaffolds have been described [15,16,17,18,19,20], effective strategies for more complex tri- and polycyclic dihydroquinazolinones, which operate under mild conditions on readily accessible simple substrates, are rare and of high value

Methods

Results

Conclusion