Cyclization precursors bicyclic dienes

Ionic hydrogenation of the same bicyclic diene 382 by Et3SiH in the presence of CF3COOH at room temperature or at 80 °C via ions 387 and 388 is accompanied by transannular cyclizations (equation 139)192. The behavior of diene 382 under Ritter reaction conditions (MeCN, H2SO4) reveals new possibilities to control the transannular cyclizations (equation 140)193. Depending on the sulfuric acid concentration, the reaction temperature and the presence of a nucleophilic solvent, these transformations can be directed to the formation of either the bicyclic amides 389 and 390 having the precursor structure or the tricyclic products 391193. 

The synthesis of the eight possible diastereoisomeric racemates of dactyl-oxene-B (44) has been carried out recently by Ohloff and co-workers (15). In the course of this work, they have observed that the spiro bicyclic ethers 46 and 49 are formed more rapidly than their C-5 epimers 47 and j>0 respectively on acid cyclization (p-TSA in CHgClg) of the hydroxy-diene precursors 45 and 48 (R- = CH3 and R3= C=CH or the opposite configuration). 

A short asymmetric synthesis of the 2-ketocarbacepham (27) involving as the initial step for the preparation of the starting piperidone, a hetero Diels-Alder reaction of the benzylimine derived from the enantiomer of Gamer s aldehyde with Danishesky s diene, has been described <02JOC598>. The key cyclization step to form the bicyclic P-lactam system was achieved from a P-amino acid precursor using the Mukaiyama reagent, 2-chloro-A-methylpyridinium iodide. 

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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