A new practical 10 step synthesis of (1S,2R)-2-acetyl-1 -methylcyclobtRaneacetic acid 15 is reported, which has as a key step a flaodium catalyzed intramolecular carbonoid cyclizstion of the ct-diazo-13-ketosuffone 5, readily available from (+)-cittonellol 2. Since 15 has already been conveRed into (+)-grandisol 1, the major pheromone of the cotton boll-weevil Anthonomus grandis, the described preparation constitutes a new formal synthesis of the optically active pheromone.
The cotton boll weevil (Anthonomus grandis Boheman) is a serious pest responsible for heavy damage to cotton crops in USA and Central America. In 1983 the pest was first detected in Brazilian cotton fields, and since then it has also become a major cause of losses to local cotton farmers. The male weevil produces an aggregation pheromone mixture whose principal component is the terpene (+)-cls-2-isopropenyl-l-methylcyclobntaneethanol (1), named (+)-grandisol. 1 Grandisol, as well as the corresponding aldehyde, grandisal, is also found in the pberomonal secretion of several other beetles. 2
The terpene has been a popular target for the synthetic orgamc chemist, not only due to its commercial importance, but also because of its interesting cyclobutane structure. The potential use of (+)-grandisol in traps for monitoring crop infestation m integrated pest management control prompted us to search for an efficient preparation of the more active 3 (+)-enantiomer.
Among the large number of preparations of 1 published to date many were devised to produce the pure (+)-enantiomer. 4 However, most of the preparations of enantiomerically pore grandisol require photochemical reactors to construct the cyclobutane ring, while others may additionally need tedious resolution, purification steps and/or use starting materials which are not easily accessible. A synthesis adequate for the production of (+)-grandisol in gram scale must obviously by-pass these limitations. Mori 4c has recently disclosed a synthetic route to (+)-1 which avoids sophisticated reactions and uses the readily avmlable (+)carvone as starting material, but purification steps and low overall yield still detract from its efficiency.
We now wish to describe a practical preparation of (+)-grandisol, which starts with the easily available 5 (+)-citronellol 2, uses conventional chemistry to make the cyclobutane ring, and avoids complicated purification procedures, since most of the intermediates are solids readily purified by simple crystallizations. Although not described in detail, the same synthetic sequence and experimental conditions ~ also carried out with racemic citronellol, with identical results. The key step in our approach is