Polycyclic Hydroxyketones

An ingenious synthesis, albeit in low yield, of 1-oxo-1,2,3,4-tetrahydro-9-hydroxyanthracene has been achieved from a phosphoran and a ketene formed as an intermediate. The phosphoran with homophthalic anhydride (3.3mols.) and trimethylsilane (3mols.) upon themolysis in toluene at 150°C for 40 hours in a sealed tube gave the product in 23% yield (ref.24). 

Pachybasin, 2-methyl-4-hydroxyanthra-9,10-quinone has been obtained in 73% yield by Diels-Alder addition from 2-bromonaphthoquinone and the vinylketene mixed acetal, 1-trimethylsiloxy-1-methoxy-3-methylbuta-1,3-diene, by reaction in dichloromethane containing potassium carbonate, heating with sodium acetate and finally aromatisation of the crude product by refluxing in ethanol The diene was accessible from methyl senecioate (methyl 3-methylbut-2-enoate) by treatment with lithium diisopropylamide and trimethylchlorosilane (ref.25). 

Substituted 2-methyl analogues were also obtained by the use of the appropriate diene. 

In the heterocyclic field, 3-carbonylmethoxypyridine-2-(4-tolyl)methylsulphoxide indicated reacted with benzylideneacetophenone in 1,1-dimethoxyethane by Michael addition in the presence of potassium t-butoxide (2.5mols.), and then cyclisation, to afford a 72% yield of 6-benzoyl-5-hydroxy-7-phenylquinoline during 24 hours at ambient temperature (ref.26). 

In another approach methytthiol as a leaving group has been used to obtain a tricyclic derivative of 2-hydroxyacetophenone. 

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The synthesis has been extended to hydroxyketones derived from polycyclic hydrocarbons (39JA1,51JA3514), steroids (71T711) and heterocycles (70JCS(C)1553), as exemplified in formulae (432)-(434), and the reaction of 7-acetyl-8-hydroxychroman and other isomers with a... 

A key step in the synthesis of 12-epi-lycopodine reported by Wiesner and coworkers is the intramolecular [2 + 2] photocycloaddition of a vinylogous imide and an allene. Irradiation of photosubstrate 46 produced a single cyclobutane 47, in which the allene added to the vinylogous imide anti to the methyl group (Scheme 13)31. Photoadduct 47 was converted to ketal-alcohol 48 via a three-step sequence of ketalization, epoxida-tion and reduction. Hydrolysis of the ketal unmasked the /Miydroxy ketone functionality. Retro-aldol fragmentation followed by aldol closure gave hydroxyketone 49, which was readily converted to the polycyclic alkaloid 12-epi-lycopodine. 

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