ANTRACENEDIOLS AS REACTIVE DIENES IN BASE-CATALYZED CYCLOADDITIONS - REDUCTION CYCLOADDITION REACTIONS OF ANTHRAQUINONES

Anthraquinone is readily reduced to the hydroquinone (9,10-anthracenediol), which under basic conditions serves as a reactive diene for cyloaddition purposes. Catalytic hydrogenation in pyridine solvent provides convenient access to this species, and efficient reactions occur with dienophiles in situ, provided that they are sufficiently reactive. Thus N-methylmaleimide (NMM) gives the bicyclic bridgehead diol in near quantitative yield when the H2/Pd reduction of anthraquinone is carried out in pyridine containing 1 equiv of NMM. Fumaronitrile and maleonitrile similarly give high yields in stereospecific reactions, with the dienophile geometry retained in the cycloadduct. Less reactive dienophiles suffer competitive reduction. Dimethyl fumarate in situ gives cycloadduct (stereospecifically) in only 35-60% yield, with the remainder of the dienophile reduced to dimethyl succinate. Stepwise reduction followed by addition of dienophile leads to a higher yield in this and related reactions. The benzologues 5,12-naphthacenedione and 6,13-pentacenedione undergo analogous reactions with NMM, leading to novel bridgehead diols. The monimine of anthraquinone exhibits NMR features attributed to syn/anti isomerism. Under neutral or mildly basic conditions, the aromatic protons on the ring proximal to the NH are clearly distinguished (500 MHz) from those on the distal ring. The addition of acid causes rapid syn/anti NH exchange leading to time averaged symmetry. This imine behaves similarly to anthraquinone in the reduction/cycloaddition sequence. For example, with NMM in situ an essentially quantitative yield of the novel bridgehead amino alcohol adduct is obtained. Related benzologue reactions and attempts to extend the sequence to the oxime and methylene analogues of anthraquinone are described. Base-catalyzed ring opening of the cycloadduct of NMM/anthracenediol leads to a novel retro-bis-aldol reaction, resulting in the formation of anthraquinone and N-methylsuccinimide.