• DOI:10.1021/jo101439h
• Corpus ID: 31659867

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.

@article{Dowling2010RingclosingMO,
  title={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.},
  author={Matthew S. Dowling and Christopher D. Vanderwal},
  journal={The Journal of organic chemistry},
  year={2010},
  volume={75 20},
  pages={
          6908-22
        }
}

• M. Dowling, C. Vanderwal
• Published 13 September 2010
• Chemistry, Biology
• The Journal of organic chemistry

The development of a strategy consisting of allylsilane ring-closing metathesis and subsequent S(E)' electrophilic desilylation (allylsilane RCM/S(E)') 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(E)' 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.