Grignard reagents coupling with allylic alcohols

Activation of allylic and propargylic alcohols. These alcohols can couple with Grignard reagents in the presence of an a-chloroenamine. For this purpose the related reagent l-chloro-2-methyl-N,N-tetramethylenepropenyIamine (2) is more effective than 1. 

Allylic chlorides are generally more useful than allylic alcohols for further synthetic operations since they are subject to SN2 displacements and, particularly, to coupling with Grignard reagents. Thus (2) on coupling with methallyl chloride in THF-HMPT gives the 1,5-diene (3) in high yield. Use of HMPT as solvent is essential for satisfactory yields. 

The reaction gives good yields with primary, secondary, and tertiary alcohols, and with alkyl and arylhthium reagents. Allylic alcohols also couple with certain Grignard reagents in the presence of a nickel complex to give both normal products and the products of allylic rearrangement. 

In addition to Ni and Pd catalysts, Li2CuCU is also an effective catalyst for the coupling of alkenyl iodides with Grignard reagents. Since the stereochemistry of alkenyl iodides is also retained, the coupling reactions are useful for the stereoselective synthesis of disubstituted alkenes, - trisubstituted al-kenes, allylsilanes, allyl alcohols and tetrasubstituted alkenes (equations 25-29). ... 

Hydroxymethylation of organic halides can bt effected by metal-catalyzed cross-coupling with the Grignard reagent (diisopropoxymcthylsilyl)methylmagnesium chloride (1) followed by oxidation. This two-step process i- particularly useful for regio- and ster-eocontrolled conversion of vinyl halides into al.ylic alcohols and of allylic halides into homoallylic alcohols. ... 

Asymmetric Coupling Reactions of Chiral Grignard Reagents Derived from Ephedrine Derivatives. Asymmetric coupling reactions of Allyl Bromide and chiral Grignard reagents derived from ephedrine methyl ether in the presence of Copper(I) Iodide (10 mol %) followed by oxidation affords optically active homoallyl alcohols with 60% ee (eq 12). ... 

Allylic alcohols do not react with alkyl- and aryl-Grignard reagents [90]. However, Swierezewski [91] reported that methyl-, phenyl-, and benzylmagnesium bromides reacted with allylic alcohols in the presence of a catalytic amount of NiCl2(PPh3)2 to give either a mixture of SN2/SN2 -coupled products, or when Ri or R2 is equal to phenyl, to the sole Sn2 compound [Eq. (91) and Table 23]. The same selectivity has been observed by Wenkerl in similar conditions [92]. 

Homoallyl bromide 314, prepared from readily available non-racemic ester 313, was converted to the Grignard reagent, which reacted with non-racemic epoxide, derived from D-maUc acid, to afford the alcohol 305. Ozonolysis of the alkene gave a ketone, which was converted into enol tri-flate 316. Ni-catalyzed cross coupling with trimethylsilylmethyl magnesium chloride afforded the allyl silane, which was converted into the allyl stan-nane 317. The asymmetric allylation of 313 with 317 provided 304 with a ration of 8.5 1. Methyl etherification and oxidative cleavage of exo-methylene... 

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