Asymmetric synthesis and Lewis acid mediated type II carbonyl ene cyclisations of (R)-2-isopropyl-5-methylhex-5-enal

The asymmetric synthesis of (R)-2-isopropyl-5-methylhex-5-enal in 98% ee is described. It was discovered that the key alkylation step employing an Eva ns chiral auxiliary and 3-methylbut-3-en-1-yl trifluoromethanesulphonate as the alkylating agent led to significant competing O-alkylation, a phenomen on not previously reported. Type II carbonyl ene cyclisation of the aldehyd e with a range of Lewis acids led to either the (R,R)- or (R,S)-5-methylide necyclohexanols without concurrent racemisation of the alpha stereogenic ce ntre of the aldehyde. Conditions for effecting the easy racemisation of a m odel enantiomerically pure aldehyde, (S)-2-methylbutanal, were developed. I n an effort to secure a dynamic kinetic resolution procedure, these conditi ons were applied to (R)-2-isopropyl-5-methylhex-5-enal. However, a competin g and dominant Prins cyclisation occurred instead leading to a mixture of a ll possible cycloadducts, all of which were obtained in 98% ee. Any unreact ed aldehyde was found to be enantiomerically pure. (C) 2000 Elsevier Scienc e Ltd. All rights reserved.