Intramolecular Hetero-Diels–Alder Reactions Catalyzed by BiCl3: Stereoselective Synthesis of Benzo-Annelated Decahydrofuro[3,2-h][1,6]naphthyridine Derivatives

Abstract

A novel, efficient synthesis of a series of functionalized, benzo-annelated decahydrofuro [3,2-h] [1,6]naphthyridine derivatives 3 has been achieved. The protocol is based on the intramolecular hetero-Diels-Alder (IMHDA) reaction of in situ formed imines derived from an N-prenylated sugar aldehyde 1 and different aromatic amines 2 in the presence of bismuth(III) chloride as catalyst. The reactions could be run under very mild conditions at room temperature, and were complete within 30 min, affording exclusively and stereoselectively the corresponding trans-fused products 3 in good-to-excellent yields (Table).Introduction. -The Diels-Alder reaction with its myriad applications has enabled the construction of complex molecules and afforded numerous unparalleled solutions to a diverse range of synthetic puzzles provided by nature in the form of natural products. Over recent years, intramolecular hetero-Diels-Alder (IMHDA) reactions have found wide application in numerous reactions of prominence in organic synthesis because of their economical and stereocontrolled nature in the synthesis of polycyclic skeletons [1] [2]. These reactions allow the formation of two or more rings at once at the expense of sequential chemical transformations.We have reported [3] several BiCl 3 -catalyzed IMHDA reactions of imines derived from O-, N-, and S-prenyl derivatives of aldehydes and anilines. However, there is no single report on IMHDA reactions using N-prenylated sugar aldehydes derived from Dglucose and amines. One possible target structure of such reactions is furo[3,2-h][1,6]naphthyridine (A), a rare and basically non-investigated heterocyclic systems, in contrast to the isomeric furo [2,3-h][1,6]naphthyridine skeleton (B), which can be readily made by Smiles rearrangement followed by cyclization [4]. These [2,3-h] [1,6]naphthyridine derivatives have shown relaxation activity against tracheal muscular contraction induced by carbamylcholine chloride.In the present work, we introduce a novel, stereoselective method for the preparation of a series of complex, tetra-or pentacyclic furo[3,2-h][1,6]naphthyridine derivatives from anilines or naphthalene-1-amine and a simple sugar derivative.

Applications of bismuth(iii) compounds in organic synthesis

“…164 The same group has employed a similar strategy for the BiCl 3 -catalyzed synthesis of naphthyridine derivatives using imines generated in situ from an N-prenylated sugar aldehyde and a variety of aromatic amines. 165 They have also reported a similar reaction between N-arylimines generated in situ from anilines and the S-allyl derivatives of pyrazole aldehydes in the presence of catalytic amounts of BiCl 3 to generate pyrazole annulated heterocycles (Scheme 99). 166 Astudillo and co-workers have applied such a strategy to the synthesis of 2,3-diaryl-2-azabicyclooctanes via BiCl 3 catalyzed aza Diels-Alder reaction between a variety of anilines, benzaldehydes and cyclohexen-2-ones (Scheme 100).…”

The Intramolecular Povarov Tool in the Construction of Fused Nitrogen-Containing Heterocycles

“…On the basis of this protocol, the same group has performed the preparation of tetra- or pentacyclic furo[3,2- h ][1,6]naphthyridine derivatives from anilines or 1-naphthylamine and a simple sugar derivative [ 42 ]. In this case, an N -prenylated sugar aldehyde 89 and different aromatic amines 18 were used in the condensation reaction to give the imines 90 (Scheme 24 ).…”