Model study:

The hydroxy group and the cyclic carbonyl function of model compound 27 were simultaneously protected as tert. butyldimethylsilyl acetal. Consequently hydrogenolysis of the benzylether yielded ketoalcohol 28. In contrast to the debenzylation product of 27, the corresponding tricyclic compound 28 did not form a highly stable hemiacetal, so that the deprotected alcohol could be transformed to the desired isobutanoate 29. In this case the isobutyl group represented an essential part of the ten membered ring to be formed.

All attempts to couple the ketoester in a McMurry or pinacol type reaction failed till now, whereas more drastic reductive conditions were successful. For example, lithium in liquid ammonia led to the vicinal diol 30 and the alcohol 31 as coupling products with major portions of the reduction product 32. Excess lithium naphthalenide in THF unfortunately yielded ketone 33 as the main product. By utilizing exactly two equivalents of lithium naphthalenide the hydroxyketone 34 was obtained in good yields. This reaction proceeded extremely fast at -78deg.C with excellent stereoselectivity (no other diastereomer could be detected, the configuration of the newly formed stereocenter was not determined so far).

Acyloin reaction type conditions (Na-K alloy, ether, trimethylsilyl chloride) led to a mixture of the silylenolethers 35.

Back to first page