Abstract
Using salicylaldehydes and β-nitrostyrenes as starting materials, 2-aryl-3-nitro-2H-chromenes were prepared in good yields (up to 83%) through the combination of 30 mol% of pyrrolidine- benzoic acid catalyzed tandem oxa-Michael-Henry reactions in refluxing ethanol. Additionally, the Michael reactions of 2-aryl-3-nitro-2H-chromenes with acetone were also performed by the same catalytic combination in brine to give 2,3,4-trisubstituted chromanes up to 86% yield with excellent stereoselectivities. The structures of 2-aryl-3-nitro-2H-chromenes and 2,3,4- trisubstituted chromanes are confirmed by X-ray single crystal diffraction analysis. The reductive amination of a suitable 2,3,4-trisubstituted chromane with Zn/HOAc affords a fused tricyclic amine in 92% yield.
Highlights
2-Aryl-3-nitro-2H-chromenes and 2,3,4-trisubstituted chromanes are important building blocks in organic synthesis and key intermediates for pharmaceutics.[1,2,3] Due to their versatile transformations in synthetic chemistry, a simple and efficient preparation of these valuable bulding blocks has drawn much attention from synthetic chemists.[4,5,6] The tandem oxa-MichaelHenry reaction of salicylaldehyde with β-nitrostyrenes is considered to be the most straightforward for preparation of 2-aryl-3-nitro-2H-chromenes
A practical and efficient synthesis of 2-aryl-3-nitro-2Hchromenes in good yields under mild conditions is still needed. 2,3,4-Trisubstituted chromanes are usually obtained through nucleophilic additions of activated 2H-chromenes with 1,3dicarbonyl compounds,[16,17] pyrrole[18] or indole.[19]
We report a facile access to 2-aryl-3-nitro-2H-chromenes through tandem oxaMichael-Henry reactions of various salicylaldehydes and β-nitrostyrenes using the combination of pyrrolidine and benzoic acid as catalyst, and the Michael additions of 2-aryl-3-nitro-2Hchromenes with acetone are firstly performed under the same catalytic combination in brine to provide multi-substituted chromanes in good yields
Summary
2-Aryl-3-nitro-2H-chromenes and 2,3,4-trisubstituted chromanes are important building blocks in organic synthesis and key intermediates for pharmaceutics.[1,2,3] Due to their versatile transformations in synthetic chemistry, a simple and efficient preparation of these valuable bulding blocks has drawn much attention from synthetic chemists.[4,5,6] The tandem oxa-MichaelHenry reaction of salicylaldehyde with β-nitrostyrenes is considered to be the most straightforward for preparation of 2-aryl-3-nitro-2H-chromenes. We report a facile access to 2-aryl-3-nitro-2H-chromenes through tandem oxaMichael-Henry reactions of various salicylaldehydes and β-nitrostyrenes using the combination of pyrrolidine and benzoic acid as catalyst, and the Michael additions of 2-aryl-3-nitro-2Hchromenes with acetone are firstly performed under the same catalytic combination in brine to provide multi-substituted chromanes in good yields. It was found that there is no transformation when benzoic acid was used as the sole catalyst, and pyrrolidine was used as sole catalyst to give 2phenyl-3-nitro-2H-chromene 3a in 32% yield (entry 1).
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