Stereochemistry Robinson annulation

Aldol addition and related reactions of enolates and enolate equivalents are the subject of the first part of Chapter 2. These reactions provide powerful methods for controlling the stereochemistry in reactions that form hydroxyl- and methyl-substituted structures, such as those found in many antibiotics. We will see how the choice of the nucleophile, the other reagents (such as Lewis acids), and adjustment of reaction conditions can be used to control stereochemistry. We discuss the role of open, cyclic, and chelated transition structures in determining stereochemistry, and will also see how chiral auxiliaries and chiral catalysts can control the enantiose-lectivity of these reactions. Intramolecular aldol reactions, including the Robinson annulation are discussed. Other reactions included in Chapter 2 include Mannich, carbon acylation, and olefination reactions. The reactivity of other carbon nucleophiles including phosphonium ylides, phosphonate carbanions, sulfone anions, sulfonium ylides, and sulfoxonium ylides are also considered. 

In analogy to Roush s earlier studies (see Scheme 14) the A-ring was incorporated by a Robinson annulation (176 177) which provided the desired stereochemistry at C-5 and C-6. Reduction then unraveled the bicyclic system to yield the expected precursor for cydization (178). Although attempts to cyclize this tetraol were unsuccessful, simple conversion of the 15-hydroxy group to the acetate (179) allowed for smooth cydization and provided the 13-nortrichothecene (180). After standard elaboration to the hydroxy diene (181) it was found that, in sharp contrast to other oxygenated trichothecenes, peracid oxidation selectively epox-idized the 12,13-double bond. This result allowed for rapid completion of the synthesis yielding the natural antipode of anguidine (9). 

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