- A Highly Efficient Synthesis of 3-Methylcholanthrene
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A five-step synthesis of 3-methylcholanthrene (1) has been achieved starting from 5-methylhomophthalic anhydride and N,N-diethyl-1-naphthamide in 55percent overall yield.Treatment of a solution of the preformed lithium enolate of 5-methylhomophthalic anhydride (3) with an equimolar solution of 2-lithio-1-naphthamide (4), followed by acid hydrolysis, provides cleanly the spirobislactone 5 in 80percent overall yield.In addition, the synthesis features a unique, highly selective double Friedel-Crafts cyclization of the aryl diacid 2 with PPA to give rise, after acetylation, to keto acetate 6.
- Gimisis, Thanasis,Koreeda, Masato
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p. 7158 - 7161
(2007/10/02)
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- Synthesis of Polycyclic Aromatic Hydrocarbons via a Novel Annelation Method
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A new general synthetic approach to polycyclic aromatic hydrocarbons is described.The method is based on the convenient availability of o-lithioarylamides from regiospecific metalation of N,N-diethylarylamides with alkyllithium-amine reagents.Addition of the o-lithioarylamide to an aryl ketone or aldehyde affords a lactone.Reduction of the latter with zinc and alkali or HI generates the free acid which undergoes cyclization with ZnCl2 and Ac2O and reduction with zinc and alkali or HI to furnish the fully aromatic polyarene.Compounds synthesized via this route include 3-methylcholanthrene, benzanthracene, dibenzanthracene, dibenzanthracene, benzopyrene, and their methyl derivatives.Overall yields are generally good.Competitive enolate anion formation depresses the yield in the initial step in the reactions of enolizable ketones.However, this pathway can be suppressed with substantial improvement in yield through deuterium exchange of the hydrogens α to the carbonyl.The last three steps of the general method can be condensed to only one step through reductive cyclization of the lactone intermediates with hydriodic acid in acetic acid.While tertiary lactones are resistant to HI under these conditions, the corresponding free acids undergo reductive cyclization under similar conditions.
- Harvey, Ronald G.,Cortez, Cecilia,Jacobs, Stephen A.
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p. 2120 - 2125
(2007/10/02)
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- SYNTHESIS OF 3-METHYLCHOLANTHRENE
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A novel synthesis of 3-methylcholanthrene is described which is operationally simpler than the method in current use and is potentially applicable to the synthesis of a wide range of other polycyclic hydrocarbons and their oxidized carcinogenic metabolites.
- Jacobs, Stephen A.,Harvey, Ronald G.
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p. 1093 - 1096
(2007/10/02)
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