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Regiospecific addition of the tin enolate nucleophile 2.99 to polysubstituted cyclohexadienyliron complex 2.45 generated diene derivative 2.104 in high yield. A substantial portion (15 out of 20 skeletal carbon atoms) of the stemodane and aphidicolane skeleta was set in place in this single operation. This reaction provided a method of joining two six-membered rings at highly substituted positions, forming contiguous quaternary carbon centers.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI). Transformation of 2.104 into aldehyde-chloride 2.134 or aldehyde-tosylate 2.129 was accomplished through a sequence of 12 synthetic manipulations. Attempts to cyclize 2.129 resulted in complicated mixtures, caused by high reactivity of the tosylate toward basic elimination and some other side reactions. In contrast, intramolecular enolate alkylation of 2.134 produced the spiro tricyclic intermediate 2.130 in excellent yield. Subsequent conversion of 2.130 into 4-nor-Δ3,4-stemodinone (2.150) was realized in 6 steps. This route represents a convergent approach to the tetracyclic framework of stemodane derivatives.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI). Two additional points in this work are also noteworthy: (1) ammonium chloride was found to considerably improve an unfavorable Claisen rearrangement of an allyl vi nyl ether intermediate; (2) a pro-C ring carbon unit for the stemodane and aphidicolane skeleta was introduced at an early stage, thus, overcoming the difficulties encountered in more traditional approaches to these molecules. |
