A formal total synthesis of 9-isocyanopupukeanane

• Main Author: Winter, Manfred
• Language: English
• Published: 2010
• Online Access: http://hdl.handle.net/2429/22563

A synthesis of (±)-9-pupukeanone (7) is described. The key reaction was the establishment of the tricyclic carbon skeleton of 7 by means of an intramolecular Diels-Alder cycloaddition. The 1,3-cyclohexanedione 48 was obtained from ethyl methacrylate and ethyl 2-methylacetoacetate by a Michael addition followed by cyclization. Treatment of 48 with isobutyl alcohol in benzene furnished the enol ether 54 which was alkylated with the tetrahydropyranyl ether of α -bromoethanol to give the ketone 55. The latter was converted into the α -enone 57 by sequential treatment with lithium aluminum hydride and acetic acid in acetone. The lithium enolate of the compound 57 could be silylated to give the silyl enol ether 60 and phosphorylated to give the enol phosphate 63. Selective tetrahydropyranyl ether cleavage in 63 with hydrochloric acid in methanol provided the alcohol 64. A similar selective de-protection of 60 to the alcohol 43 could not be accomplished. The aldehyde 65 was synthesized from the alcohol 64 by a Moffatt-type oxidation of the latter. The nitrile 76 was obtained from the aldehyde 65 in 2 steps via the corresponding oxime. Reaction of 65with vinyllithium or vinyl magnesium bromide furnished the allylic alcohol 69 which, upon reflux in xylene, smoothly cyclized to the Diels-Alder adduct T8. The allylic alcohol 69 could not be oxidized to the α -enone 71. The enol phosphate 78 was converted into the keto alcohol 18 with sodium ethoxide in ethanol. Treatment of either the alcohol 78 or 18 with 2,2-dimethyl-l ,3-propanediol in benzene provided the ketal alcohol 86 which could be cleanly oxidized to the ketal ketone 87 with pyridinium dichromate. Addition of isopropenyllithium to 87 generated the tertiary alcohol 90. The diene 20 was obtained from 90 by simultaneous dehydration and deketalization with boron trifluoride etherate. Hydrogenation of the compound 20 with iridium black as catalyst furnished a sample of 9-pupukeanone (7). The alcohol 78 was oxidized with pyridinium dichromate to the ketone 96, which, upon reaction with 2,4,6-triisopropylbenzene-sulfonylhydrazide, provided the trisylhydrazone 97. The compound 97 could not be induced to decompose to a vinyl lithium intermediate by treatment with butylithium. [See thesis for diagrams]. === Science, Faculty of === Chemistry, Department of === Graduate