取代薁酮的反应性研究：秋水仙碱合成新策略的探索

Reactivities of Substituted Azulenone: Strategic Exploration on the Novel Synthesis of Colchicine

本工作以探索秋水仙碱(Colchicine)合成新策略为目标,研究了烷氧基取代薁酮2a的独特反应性,发现了一系列罕见的重排过程和环庚三烯(Tropilidene)降蒈二烯(Norcaradiene)互变异构现象,探讨了相应的反应机理.

Strategic exploration towards a novel synthesis ofcolchicine based on the angular aryl-substituted azulenone 2a is reported. Unique reactivities of 2a are documented in this report which features the valency tautomerization of tropilidene norcaradiene. The starting azulenone 2a was readily prepared by an unusual condensation of bis-（trimethoxy）phenylketene with ethoxyacetylene according to an earlier discovery by Nieuwenhuis and Arens in 1958. Although the mechanism of this transformation was rationalized later by Woodward and Barton respectively, the synthetic value of this reaction has not been demonstrated so far. We envisioned an interesting strategy towards the synthesis of eolchicine via an addition-ring expension pathway （2b --4 2e）. Hydride reduction of 2a followed by acidolysis afforded a spirocycle 4 instead of the anticipated azulenone intermediate 2b, via presumably the vanlency tautomer 3a. Upon further hydride reduction and acidic hydrolysis 4 was converted into the rearranged azulenone 5 along with naphthalene 6. Treatment of azulenone 5 with triflic acid led to a bridge cyclic enone 8, a facile Friedel-Crafts type cyclization product. While mild acidic conditions resulted in the cleavage of the fused cyclopentenone. Azulenone 13 was readily prepared from 2a via partial hydrogenation, hydride reduction, and acidolysis. Upon treatment with triflic acid, 13 was transformed into the angular aryl-shifted enone 14 stereospecifically, via presumably a cationic cyclopropane intermediate 15. In summary, although azulenone derivatives 5 and 13 synthesized from 2a did not undergo the planned transformation, other intriguing reactivity patterns were revealed.