Part I. The total synthesis of (+)-trehazolin: Optically active spiroheptadienes as useful precursors for the synthesis of aminocyclopentitols. Part II. An inexpensive, nonbasic alternative to the Horner-Emmons olefination reaction

Polysubstituted cyclopentyl rings are a common structural feature in nature. Densely functionalized five-membered carbocycles feature prominently in many natural products. Because of this ubiquity, a versatile synthon for the construction of enantiomerically pure polyfunctional cyclopentanes would be a valuable addition to the armamentium of the organic chemist. We believed that spiro[2.4]hepta-4,6-diene-1-methanol could fill this role. As a demonstration of the power of this synthon, we describe a total synthesis of the trehalase inhibitor trehazolin. The synthesis of the trehalase inhibitor trehazolin is fairly concise; the fully functionalized aminocyclitol core is prepared in just 14 steps. Highlights include (1) preparation of optically active spiro[2.4]hepta-4,6-diene-1-methanol, (2) one-step aminohydroxylation of the cyclopentadiene moiety, (3) imidate opening with Li2NiBr 4, and (4) the use of 1,6-anhydro-beta-D-glucose in the preparation of the glycosylating agent. Optically active spiro[2.4]hepta-4,6-diene-1-methanol and its derivatives should prove valuable in the construction of other cyclopentanoid natural products.;A number of important enantioselective processes utilize allylic relationships to install chirality, and the Horner-Emmons olefination reaction has long been the gold standard for the stereoselective synthesis of these substrates from aldehydes and ketones. It was recently reported by Herrmann and coworkers that methyltrioxorhenium was capable of catalyzing the olefination of aldehydes with ethyl diazoacetate in the presence of a stoichiometric amount of triphenyl phosphine. We found that triethyl phosphite was capable of both reducing Re(VII) and promoting the reaction. With as little as 1% catalyst, a wide variety of aldehydes were converted into the corresponding (E)-enoates efficiently. An extremely mild, inexpensive alternative to the Horner-Emmons reaction has been described. The chemoselectivity of this process (aldehyde vs. ketone) should prove useful in organic synthesis.