Tandem dinucleophilic cyclization of cyclohexane-1,3-diones with pyridinium salts

Mostafa Kiamehr,Linda Supe,Firouz Matloubi Moghaddam,Satenik Mkrtchyan,Viktor O Iaroshenko,Alexander Villinger,Peter Langer,Volodymyr Semeniuchenko

doi:10.3762/bjoc.9.124

Abstract

The cyclization of cyclohexane-1,3-diones with various substituted pyridinium salts afforded functionalized 8-oxa-10-aza-tricyclo[7.3.1.02,7]trideca-2(7),11-dienes. The reaction proceeds by regioselective attack of the central carbon atom of the 1,3-dicarbonyl unit to 4-position of the pyridinium salt and subsequent cyclization by base-assisted proton migration and nucleophilic addition of the oxygen atom to the 2-position, as was elucidated by DFT computations. Fairly extensive screening of bases and additives revealed that the presence of potassium cations is essential for formation of the product.

Highlights

The nucleophilic addition to pyridinium salts has recently been proven to be a powerful method for the construction of various dihydropyridines [1,2,3,4], which are valuable intermediates in organic synthesis [5,6,7,8,9,10,11,12], and interesting compounds in medicinal [13] and bioorganic chemistry [14,15,16]
During the course of the above-mentioned study we discovered an interesting reaction that represents an external dinucleophilic addition of the dimedone molecule to the pyridinium salt 2a, taken as a random example, delivering 8-oxa-10-azatricyclo[7.3.1.02,7]trideca-2(7),11-diene (3a) in modest yield (Scheme 1)
We studied the reaction of pyridinium salt 2a with dimedone (1a) using various bases in different solvents (Table 1)

Summary

Introduction

The nucleophilic addition to pyridinium salts has recently been proven to be a powerful method for the construction of various dihydropyridines [1,2,3,4], which are valuable intermediates in organic synthesis [5,6,7,8,9,10,11,12], and interesting compounds in medicinal [13] and bioorganic chemistry [14,15,16]. During the course of the above-mentioned study we discovered an interesting reaction that represents an external dinucleophilic addition of the dimedone molecule to the pyridinium salt 2a, taken as a random example, delivering 8-oxa-10-azatricyclo[7.3.1.02,7]trideca-2(7),11-diene (3a) in modest yield (Scheme 1). We studied the reaction of pyridinium salt 2a with dimedone (1a) using various bases in different solvents (Table 1).

Results

Conclusion