Synthesis of 4-Substituted-1,2-Dihydroquinolines by Means of Gold-Catalyzed Intramolecular Hydroarylation Reaction of N-Ethoxycarbonyl-N-Propargylanilines.

Antonio Arcadi,Andrea Fochetti,Federico Marrone,Antonella Goggiamani,Antonia Iazzetti,Giancarlo Fabrizi,Vincenzo Marsicano,Giulia Mazzoccanti,Andrea Serraiocco,Andrea Calcaterra

doi:10.3390/molecules26113366

Antonio Arcadi, Andrea Fochetti + Show 8 more

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https://doi.org/10.3390/molecules26113366

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Abstract

An alternative Au(I)-catalyzed synthetic route to functionalized 1,2-dihydroquinolines is reported. This novel approach is based on the use of N-ethoxycarbonyl protected-N-propargylanilines as building blocks that rapidly undergo the IMHA reaction affording the 6-endo cyclization product in good to high yields. In the presence of N-ethoxycarbonyl-N-propargyl-meta-substituted anilines, the regiodivergent cyclization at the ortho-/para-position is achieved by the means of catalyst fine tuning.

Highlights

4-Substituted-1,2-dihydroquinolines represent key structural units in a variety of naturally occurring products/pharmaceuticals and are used as building blocks in organic synthesis [1,2,3,4,5]
The transition metal-catalyzed as well as the metal-free mediated intramolecular hydroarylation (IMHA) reactions involving the activation of the N-substituted-Npropargyl anilines carbon–carbon triple bond by using an electrophilic source have been extensively used [12,13]
While N-propargylanilines bearing the more removable 2nitrobenzenesulfonyl (Ns) nitrogen protecting group underwent the gold-catalyzed IMHA to give the corresponding dihydroquinoline in good yield, subjection of the N-Boc protected derivatives under the same reaction conditions afforded the divergent formation of an oxazolidinone derivative as the exclusive product [16]

Summary

Introduction

4-Substituted-1,2-dihydroquinolines represent key structural units in a variety of naturally occurring products/pharmaceuticals and are used as building blocks in organic synthesis [1,2,3,4,5]. The synthetic potential of gold catalysis in the IMHA of N-tosyl-N-propargylanilines was explored and the corresponding 4-substituted1,2-dihydroquinoline derivatives were efficiently isolated (Scheme 1a) [14,15,16]. These latter products can be obtained by the sequential catalyzed IMHA/Pdcatalyzed cross-coupling of 3-bromo-2-propynyl-N-tosylanilines, which afforded the corresponding 4-substituted-1,2-dihydroquinoline derivatives [17,18]. While N-propargylanilines bearing the more removable 2nitrobenzenesulfonyl (Ns) nitrogen protecting group underwent the gold-catalyzed IMHA to give the corresponding dihydroquinoline in good yield, subjection of the N-Boc protected derivatives under the same reaction conditions afforded the divergent formation of an oxazolidinone derivative as the exclusive product [16].

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Conclusion