Synthesis of exo-methylidenecycloalkanes via allylsilane ring-closing metathesis/SE' electrophilic desilylation. Short syntheses of teucladiol, poitediol, dactylol, and 4beta,6beta-dihydroxy-1alpha,5beta(H)-guai-9-ene (isoteucladiol)

In part I, the development of a novel strategy for constructing exo-methylidenecycloalkanes, which are embedded in many terpenoid natural products, is described. The two-step strategy involves allylsilane ring-closing metathesis and subsequent SE' electrophilic desilylation (allylsilane RCM/SE'). The power of this strategic combination of reactions is documented in short syntheses of the sesquiterpenes teucladiol and poitediol. The flexibility of the allylsilane RCM/SE' strategy is demonstrated through the synthesis of the natural products dactylol and 4beta,6beta-dihydroxy-1alpha,5beta(H)-guai-9-ene (isoteucladiol) from late-stage intermediates en route to poitediol and teucladiol, respectively.;Teucladiol was synthesized in both racemic and enantioenriched forms, which allowed the absolute configuration of natural teucladiol to be established. The syntheses of (+/-)-teucladiol and (--)-teucladiol both required five steps from aldehyde 3.34, and proceeded in 28% and 16% overall yield, respectively. The synthesis of poitediol demonstrates the power of the allylsilane RCM/SE' strategy for synthesizing exo-methylidenecyclooctanes, in this case with the simultaneous stereoselective incorporation of an allylic hydroxy group. The synthesis of poitediol was accomplished in seven steps and 18% overall yield.;Efforts toward incorporating the allylsilane RCM/SE' sequence into total syntheses of caryophyllene and oxypterine are also disclosed. The efforts directed toward caryophyllene resulted in the identification of a novel metal alkylidene-promoted deallylation reaction of terminal 1,4-dienes.;In part II, efforts directed toward constructing the core architectures of the pauciflorine and tenuisine families of Kopsia alkaloids are described. A biogenetically inspired plan for converting the pauciflorine core in the core architecture of the tenuisine, lundurine, and lapidilectine families of Kopsia alkaloids is advanced.;The synthetic plan for constructing the pauciflorine core features a challenging type II intramolecular Diels--Alder (type II IMDA) reaction. While the substrate for this transformation was constructed, it failed to undergo the desired type II IMDA reaction. Several strategies for constructing the core architecture of the tenuisine family of Kopsia alkaloids were pursued. In one set of approaches, the key step constituted an intramolecular SmI2-mediated cyclization to forge the indoline C--C bond. Another approach sought to employ a Nozaki--Hiyama--Kishi reaction to accomplish the same task. Neither of these strategies was successful.