An Approach to the Total Synthesis of Dendrobine

Article abstract of DOI:10.1021/jo00221a033

The possible rearrangement of a 5-azatricyclo<6.1.1.0^5,9>decane immonium ion (3) to the 2-azatricyclo<5.2.1.0^4,10>decane carbocation 5 has been investigated as a route to the physiologically potent alkaloid dendrobine (1). tert-Butyl acetoacetate is converted in seven steps and 40percent overall yield into cyclopentenone 15, which undergoes intramolecular <2 + 2> photoaddition to the tricyclic ketone 16.The structure of this material was vouchsafed by single-crystal X-ray analysis of the crystalline oxime, 18.Methanolysis of the oxime benzoate 20 provides nitrile ester 21, which is transformed by straightforward operations into lactam 24.Reduction of 24 gives an immonium ion, which may be trapped as amino nitrile 26.However, the immonium ion shows no propensity to rearrange to the 2-azatricyclo<5.2.1.0^4,10>decane system.To provide a more reactive immonium ion, oxime 18 was converted into carbinol amides 34a and 34b (six steps, 54percent overall yield).Solvolysis of this material in 95percent formic acid yields rearranged alkene 38, tertiary formate 41, alcohol 40, and secondary formate 44.When the rearrangement is carried out at 100 deg C, compound 44 may be isolated in 55percent yield.Lithium aluminum hydride reduction of 44 provides crystalline amino alcohol 45.The structure of this material was firmly established by extensive proton NMR studies and single-crystal X-ray analysis.A likely mechanism for the rearrangement of 34 to 44 is put forth, and plans for the eventual use of the rearrangement in a dendrobine synthesis are discussed.