Ring-Closing Metathesis of Allylsilanes As a Flexible Strategy toward Cyclic Terpenes. Short Syntheses of Teucladiol, Isoteucladiol, Poitediol, and Dactylol and an Attempted Synthesis of Caryophyllene
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- 作者：Matthew S. Dowling ; Christopher D. Vanderwal
- 刊名：Journal of Organic Chemistry
- 出版年：2010
- 出版时间：October 15, 2010
- 年：2010
- 卷：75
- 期：20
- 页码：6908-6922
- 全文大小：1377K
- 年卷期：v.75,no.20(October 15, 2010)
- ISSN：1520-6904
文摘
The development of a strategy consisting of allylsilane ring-closing metathesis and subsequent S<sub>Esub>′ electrophilic desilylation (allylsilane RCM/S<sub>Esub>′) to construct exo-methylidenecycloalkanes is described. Its utility is documented in short syntheses of teucladiol and poitediol. A key transformation in the synthesis of teucladiol is an aldol addition that establishes three stereochemical relationships in one step with ≥10:1 diastereoselectivity and provides a fascinating example of double stereodifferentiation/kinetic resolution with racemic reaction partners in the context of natural product synthesis. The synthesis of (±)-teucladiol required five steps from cyclopentenone and proceeded in 28% overall yield; adaptation of this route to an enantioselective synthesis of (−)-teucladiol enabled the determination of the absolute configuration of this terpene natural product. The use of fluoride-mediated conditions in the final desilylation step preserves the location of the alkene, delivering the natural product (±)-isoteucladiol (five steps and 21% yield from cyclopentenone). The synthesis of poitediol showcases the power of RCM for constructing eight-membered rings and features a highly diastereoselective epoxidation/fluoride-mediated fragmentation sequence for installing the exo-methylidene group with an adjacent hydroxyl-bearing stereocenter. The synthesis of (±)-poitediol required seven steps and proceeded in 18% overall yield. Again, fluoride-mediated desilylation of a late-stage intermediate (with retention of double-bond location) delivered the natural product (±)-dactylol (seven steps and 24% yield). Efforts directed toward incorporating the RCM/S<sub>Esub>′ sequence into a synthesis of caryophyllene are also disclosed. While ultimately unsuccessful, these efforts resulted in the identification of a novel metal alkylidene-promoted deallylation reaction of terminal 1,4-dienes. A possible mechanism for this unexpected deallylation reaction of 1,4-dienes is provided.