Homoallylic trifluoromethylated

Difluoromethyl proline has been prepared by a related approach. Synthesis of cis- and fra 5-4-trifluoromethyl-D-prolines has been performed starting from the Garner aldehyde. 4-Trifluoromethyl, difluoromethylene, or difluoromethyl prolines could also be prepared by 5-endo-trig cyclization of A-(homoallyl)-sulfonamides. ... 

Nagai, T. Nishioka, G. Koyama, M. Ando, A. Miki, T. Kumadaki, I. Reactions of trifluoromethyl ketones. IX. Investigation of the steric effect of a trifluoromethyl group based on the stereochemistry on the dehydration of trifluoromethyl homoallyl alcohols./. Fluorine Chem. 1992, 57, 229-237. 

A highly stereoselective synthesis of trifluoromethylated homoallylic alcohols is possible using the transmetallation [Sn(II) to In(IIl)] pathway [205], The indium trichloride/tin-promoted reaction of trifluorobromobutene with various aldehydes afforded the homoallylic alcohols in extremely high yield and diastereos-electivity (Scheme 10-105). The strong preference for the anti products with the simple aldehydes is expected on the basis of previous observations with 2-buteny-lindium reagents explained by the cyclic transition structure xxxiv shown. The syn homoallylic alcohol was obtained upon reaction of glyoxylic acid and 2-pyri-dinyl carboxaldehyde. The syn products were proposed to arise by reaction via the 5-membered chelate transition structures xxxv and xxxvi. 

Indium-mediated reachon of 4-bromo-l,l,l-trifluoro-2-butene with aldehydes in water proceeds stereoselectively to afford the -trifluoromethylated homoallylic alcohols selectively (Scheme 8.4) [18]. 

Bu3Bi mediates the allylation of carbonyl compounds with allyl bromide to give a mixture of homoallyl alcohols and fheir allyl ethers (Scheme 14.133) [278], Tris(4-methoxyphenyl)bismuthane catalyzes the cyanation of carbonyl compounds with MesSiCN [175], In the presence of fluoride ions (CeFsjsBi undergoes nucleophilic substitution with an activated C-F bond of perfluorinated compounds to transfer three CgFj groups [279]. (CFsjsBi can also act as a trifluoromethyl anion equivalent [280]. 

A tin-mediated, indium trichloride promoted allylation reaction provided P-trifluoromethylated homoallylic alcohols, the building blocks of biologically active substances, in high yields and excellent stereoselectivity (R=H, Cy, Ar, COOH) (Scheme 8.25). Since the syntheses can be carried out in water, the reactive OH groups do not need to be protected, and even compounds that are insoluble in organic solvents can be used [36]. 

On the other hand, the couphng of methyl (Z)-2-(bromomethyl)-2-butenoate with the aldehyde under the same conditions generated the desired homoallylic alcohol in 80% yield with a high 93 7 syn/anti selectivity (Eq. 4.21). The indium-mediated aUylation of triflu-oroacetaldehyde hydrate (R = H) or trifluoroacetaldehyde ethyl hemiacetal (R = Et) with an aUyl bromide in water yielded a-trifluoromethylated alcohols. Lanthanum triflate-promoted indium-mediated allylations of aminoaldehydes in aqueous media generated j8-aminoalcohols stereoselectively. Indium-mediated intramolecular carbocychzation in aqueous media generated fused Q -methylene-y-butyrolactones. An advanced intermediate for azaspiracids was only accessible by the indium-mediated aUylation. Other potentially reactive functionalities, such as azide, enone, and ketone, did not interfere with the reaction. 

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