Ring-Closing Metathesis of Allylsilanes As a Flexible Strategy toward Cyclic Terpenes. Short Syntheses of Teucladiol, Isotencladiol, Poitediol, and Dactylol and an Attempted Synthesis of Caryophyllene

The development of a strategy consisting of allylsilane metathesis and subsequent S-1 ' electrophilic desilylation (allylsilane RCM/S-E') to construct exo-methylideneeycloalkanes is described Its utility is documented in short syntheses of teucladiol and portediol A key transformation in the synthesis of teucladiol is an aldol addition that establishes three stereochemical relationships in one step with a >= 10 1 diastereoselectivity and provides a fascinating example of double stereodifferentiation/kinetic resolution with racemic reaction partners in the context of mutual product synthesis The synthesis of (+/-)-teucladiol required live steps from cyclopentenone and proceeded in 28% overall yield adaptation of this mute 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 I nip 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 mutual product (+/-)-dactylol (seven steps and 24% yield) Efforts directed toward memporating the RCM/SE' 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 4-dienes A possible mechanism or this unexpected deallylation reaction of 1,4-dienes is provided