Grignard reagents allylic acetals

In the 1952 paper mentioned above [3], Gilman reported on the formation of lithium dimethylcuprate from polymeric methylcopper and methyllithium. These so-called Gilman cuprates were later used for substitution reactions on both saturated [6] and unsaturated [7, 8, 9] substrates. The first example of a cuprate substitution on an allylic acetate (allylic ester) was reported in 1969 [8], while Schlosser reported the corresponding copper-catalyzed reaction between an allylic acetate and a Grignard reagent (Eq. 2) a few years later [10]. 

Initial studies on the application of these catalysts to allylic substitution reactions showed that the arenethiolate moiety functions as an excellent nontransferable group, and that the regioselectivity can be completely reversed by suitable changes in the reaction parameters [33]. If the reaction between geranyl acetate and n-BuM gl was carried out inTHFat—30°C with fast addition of the Grignard reagent to the reaction mixture, complete a selectivity was obtained. Raising the tempera-... 

The effect of the leaving group was briefly examined, but cinnamyl bromide gave a substantially lower ee (38%). Cinnamyl dimethyl phosphonate, or acetate, gave very poor results. The cyclohexyl-substituted allylic acetate 21, on the other hand, afforded a completely y-selective reaction, but the product turned out to be racemic. Changing the Grignard reagent halide from bromide to either chloride or iodide resulted in very low ees. 

Although an a-CF3 group is known to retard. S n2 reactions of carbon nucleophiles with alkyl sulfonates, it has now been found that y-trifluoromethylated allylic acetals undergo 5k2 -type reactions with Grignard reagents in presence of catalytic amounts of CuCN and TMS-C1 without formation of 5N2 products.110 This provides an alternative means of introducing a carbon nucleophile adjacent to a CF3 group. 

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