Christian Bittner

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

The asymmetric synthesis of enantiomerically pure a-substituted tertiary homoallylic ethers 4a, 11 and 12a-c by the allylation of ethyl methyl ketone (la) with gamma-substituted allylsilanes 9a-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 la 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 4a, 11 and 12a-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.

Synthesis of Enantiopure Homoallylic Ethers by Reagent Controlled Facial Selective Allylation of Chiral Ketones

The stereoselective allylation of chiral methyl ketones to give tertiary homoallylic ethers, which can easily be transformed into homoallylic alcohols, is described. Reaction of the enantiopure ketones 8a-d and the racemic ketones 26a-d with the norpseudoephedrine derivative 2 or ent-2 and allylsilane in the presence of a catalytic amount of trifluoromethanesulfonic acid, led to a series of homoallylic ethers with good to excellent diastereoselectivity (85:15 to > 97:3). The allylation is reagent controlled and nearly independent from the stereogenic centers in the substrates. A partial kinetic resolution was observed using the racemic ketones 26a-d. In the reaction of the chiral ketones 8a-d with the achiral reagents ethoxytrimethylsilane and allylsilane only a low diastereoselectivity was observed.