Preparation of amino-substituted indenes and 1,4-dihydronaphthalenes using a one-pot multireaction approach: total synthesis of oxybenzo[c]phenanthridine alkaloids.

Ewen D D Calder,Andrew Sutherland,Fiona I Mcgonagle,Grant A Mcgonagle,Alexander H Harkiss

doi:10.1021/jo5014492

Ewen D D Calder, Andrew Sutherland + Show 3 more

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https://doi.org/10.1021/jo5014492

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Journal: The Journal of organic chemistry	Publication Date: Aug 1, 2014
Citations: 30	License type: cc-by

Affiliation: University of Glasgow

Abstract

Allylic trichloroacetimidates bearing a 2-vinyl or 2-allylaryl group have been designed as substrates for a one-pot, two-step multi-bond-forming process leading to the general preparation of aminoindenes and amino-substituted 1,4-dihydronaphthalenes. The synthetic utility of the privileged structures formed from this one-pot process was demonstrated with the total synthesis of four oxybenzo[c]phenanthridine alkaloids, oxychelerythrine, oxysanguinarine, oxynitidine, and oxyavicine. An intramolecular biaryl Heck coupling reaction, catalyzed using the Hermann-Beller palladacycle was used to effect the key step during the synthesis of the natural products.

Highlights

Occurring benzo[c]phenanthridines belong to an extensive family of isoquinoline alkaloids, many of which have important biological activities.[1]
One-Pot Multireaction Processes for the Preparation of Amino-Substituted Indane and Naphthalene Ring Systems substituted indanes and tetrahydronaphthalenes were formed following a one-pot Diels−Alder reaction and oxidation step using alkynes and 1,4-quinones as dienophiles. While this approach allowed the flexible synthesis of various ring sizes and the late stage incorporation of aromatic ring substituents, we found that only a limited number of electron-deficient alkynes participated in the Diels−Alder reaction, restricting the variety of compounds produced
As well as demonstrating the scope of this process, we describe its application for the total synthesis of the oxybenzo[c]phenanthridine alkaloids oxychelerythrine (1), oxysanguinarine (2), oxynitidine (3), and oxyavicine (4)

Summary

■ INTRODUCTION

Occurring benzo[c]phenanthridines belong to an extensive family of isoquinoline alkaloids, many of which have important biological activities.[1]. One-Pot Multireaction Processes for the Preparation of Amino-Substituted Indane and Naphthalene Ring Systems substituted indanes and tetrahydronaphthalenes were formed following a one-pot Diels−Alder reaction and oxidation step using alkynes and 1,4-quinones as dienophiles While this approach allowed the flexible synthesis of various ring sizes and the late stage incorporation of aromatic ring substituents, we found that only a limited number of electron-deficient alkynes participated in the Diels−Alder reaction, restricting the variety of compounds produced. A one-pot, two-step multireaction process involving an Overman rearrangement and a ring-closing metathesis (RCM) reaction would allow a more direct synthesis of these ring systems.[12] In addition, the general availability of 2-bromobenzaldehydes would result in the preparation of a wider range of potential products, and the formation of cyclic allylic amides from this particular one-pot process (cf Scheme 1a) would give an additional functional handle for further transformations of these compounds. As well as demonstrating the scope of this process, we describe its application for the total synthesis of the oxybenzo[c]phenanthridine alkaloids oxychelerythrine (1), oxysanguinarine (2), oxynitidine (3), and oxyavicine (4)

■ RESULTS AND DISCUSSION

■ CONCLUSIONS

■ REFERENCES