Regioselective reactions of 1,4,5-trihydroxy-9,10-anthraquinone

The regioselective alkylation of 1,4,5-trihydroxy-9,10-anthraquinone via reaction of its leuco compound is significant for the synthesis of anthracyclinones. In the presence of pyrrolidine in toluene solution, the leuco compound 3 selectively forms the 4-pyrrolidino enamine 11 , which undergoes deamination to give 1,5-dihydroxy-9,10-anthraquinone. If an aldehyde is added, however, the enamine is alkylated, eventually yielding the 3-alky 1-1,4,5-trihydroxy-9,10-anthraquinone. Both of the above reactions of 3 give high yields with 100% regioselectivity. The enamine intermediate 11 has been trapped by oxidation to 4-pyrrolidino-1,5-dihydroxy-9,10-anthraquinone, which, after reduction, undergoes the same reactions as 3 giving either the alkylation or deamination product. The selective formation of 11 is explained in terms of an enhancement of carbonyl group electrophilicity by a relay of hydrogen bonds.