Facial-Selective Allylation of Methyl Ketones for the Asymmetric Synthesis of -Substituted Tertiary Homoallylic Ethers

Abstract

The asymmetric synthesis of enantiomerically pure α-substituted tertiary homoallylic ethers 4 a, 11 and 12 a–c by the allylation of ethyl methyl ketone (1 a) with γ-substituted allylsilanes 9 a–h is described. The allylsilanes were obtained by a nickel-catalysed Grignard cross-coupling reaction of (E)- and (Z)-(3-iodoallyl)trimethylsilane with various Grignard reagents. The reaction of the allylsilanes with 1 a in the presence of the trimethylsilyl ether of N-trifluoroacetylnorpseudoephedrine (3), and catalytic amounts of a mixture of trimethylsilyl triflate and trifluoromethanesulfonic acid led to the homoallylic ethers 4 a, 11 and 12 a–c with two new stereogenic centres, with a selectivity of 1:9 to >20:1 for the homoallylic and of 1:99 to >60:1 for the allylic centre. The facial selectivity does not depend on the configuration of the allylsilane, and in all reactions the anti product is preferentially formed. Interestingly, a pronounced switch of facial selectivity takes place with increasing length of the alkyl group of the allylsilane.