Synthesis of 8-substituted 1,5-diazabicyclo[3.2.1]octane derivatives via double aza-Michael addition of homopiperazine to 3-trifluoroacetyl-4 H -chromenes

The reaction of homopiperazine with 2-trifluoroacetyl-1H-benzo[f]chromenes affords 2-(1,5-diazabicyclo[3.2.1]octan-8-yl)-3-(trifluoromethyl)-2,3-dihydro-1H-benzo[f]chromen-3-ols, while 3-trifluoroacetyl-4H-chromenes give 2-[2-(1,5-diazabicyclo[3.2.1]octan-8-yl)ethyl]phenols. Both reactions are the first examples of synthesis of 1,5-diazabicyclo[3.2.1]octane core via double Michael addition and include cascade Michael addition/pyran ring opening/Michael addition.