P. Kraft, K. Popaj
2008
Citations
0
Influential Citations
6
Citations
Journal
European Journal of Organic Chemistry
Abstract
To study the olfactory properties of spirocyclic analogs of Iso Gamma (3) with improved water solubility and bioavailability, it was envisaged to spiroannulate 1-acetyl-1,2-dimethylcyclohexanone at the 4-position with a 3,3-dimethyltetrahydrofuran-2-yl moiety that would mimic the polarity of the double bond by its ether function. 3,3-Dimethyl-4-methylenehex-5-en-1-ol (9) was prepared by copper(I)-mediated 1,4-conjugate addition of the Grignard reagent of chloroprene (7) to 3-methylbut-2-enal with subsequent LAH reduction. However, the Diels–Alder reaction of diene 9 with (E)-3-methylpent-3-en-2-one in the presence of Me2AlCl unexpectedly provided exclusively the undesired meta adduct 10, as was discovered after cyclization to 11 with MeSO3H. The wrong selectivity was due to a tethering effect of the Lewis acid, and this could be evaded by changing the carbonyl function of the dienophile to a hydroxy group. Thereby the (5′R*,7′S*,8′S*)-configured 1-(4′,4′,7′,8′-tetramethyl-1′-oxaspiro[4.5]decan-7′/8′-yl)ethan-1-ones 11 and 14, as well as the like-configured 1-(4′,4′,7′-trimethyl-1′-oxaspiro[4.5]decan-7′/8′-yl)ethan-1-ones 16 and 19, were prepared selectively and studied for their odor characters, threshold values, and octanol/water partition coefficients. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)