Selective Partial Reduction of Various Heteroaromatic Compounds with Bridgehead Nitrogen via Birch Reduction Protocol

2005-03-18T00:00:00Z (GMT) by Joseph T. Kim Vladimir Gevorgyan
For the first time various heteroaromatic compounds with bridgehead nitrogen, including indolizines, bispyrrolopyrimidines, pyrroloquinolines, pyrroloisoquinolines, and bispyrrolopyrazines, were selectively partially reduced under Birch reduction conditions. It was found that the double bond in the fused heterocycles which possesses the highest LUMO density can be selectively reduced under these conditions. Indolizine <b>6</b>, containing an ester group at C-6, was reductively alkylated to give dihydroindolizines <b>8 </b>and <b>9</b> possessing a quaternary carbon center in good yield. It was found that ambident substrate <b>12</b>, under Birch reduction conditions, underwent smooth partial reduction to give 4,5-dihydroquinoline <b>14</b> as a sole product with no evidence of reduction of the side chain olefin. It was also shown that electron-rich pyrroloisoquinoline <b>15</b>, which cannot be reduced via catalytic hydrogenation conditions, was efficiently transformed into its dihydrocounterpart <b>16</b> by using the Birch reduction protocol. Finally, it was shown that various fused diazines were smoothly and stereoselectively reduced under Birch reduction conditions to give <i>trans</i>-4,5-disubstituted dihydropyrimidines <b>30</b> and <b>32 </b>in virtually quantitative yields.