Asymmetric cross-coupling chlorides

Optically active (Z)-l-substituted-2-alkenylsilanes are also available by asymmetric cross coupling, and similarly react with aldehydes in the presence of titanium(IV) chloride by an SE process in which the electrophile attacks the allylsilane double bond unit with respect to the leaving silyl group to form ( )-s)vr-products. However the enantiomeric excesses of these (Z)-allylsilanes tend to be lower than those of their ( )-isomers, and their reactions with aldehydes tend to be less stereoselective with more of the (E)-anti products being obtained74. 

Trimethyl(l-phenyl-2-propenyl)silane of high enantiomeric excess has also been prepared by asymmetric cross coupling, and reacts with aldehydes to give optically active products in the presence of titanium(IV) chloride. The stereoselectivity of these reactions is consistent with the antiperiplanar process previously outlined75. 

A catalytic version of the coupling was also developed, by using 10 mol % of CuCl2 and 20 mol % of sparteine 1 (silver chloride was used as a stoichiometric oxidant to regenerate the copper (II) oxidant). This catalytic system was applied to the asymmetric cross-coupling leading to 101 in a 41% yield and 32% ee. 

In the late 1970s and early 1980s, Kumada described nickel-catalyzed asymmetric cross-coupling reactions of 1-arylethylmagnesium chlorides with vinyl bromide in... 

A polystyrene-bound chiral aminophosphine-Ni(II) chloride complex catalyzes the asymmetric cross-coupling reaction of a secondary alkyl Grignard reagent with vinyl bromide in a moderate optical yield (25). 

An example of practical application of the asymmetric cross-coupling, enantioselective synthesis of a-curcumene (19), is shown in Scheme 8F.6 [21]. The compound was synthesized with 66% ee through Ni/(S)-(/ )-PPFA (lOa)-catalyzed cross-coupling of 1 -(p-tolyl)ethylmag-nesium chloride (17) and vinyl bromide (4b). 

The asymmetric cross-coupling of 1-phenylethylmagnesium chloride 20a with vinyl bromide 21 a has been reported by Hayashi and Kumada to proceed in the presence of 0.5 or 1 mol% of nickel or palladium catalyst coordinated with a chiral ferrocenylphosphine ligand to give optically active 3-phenyl-1-butene 22 [28]. 

After these findings, asymmetric cross-coupling of the secondary alkyl (jrignard reagents has been attempted using various kinds of optically active phosphine ligands. The reaction most extensively studied so far is that of 1-phenylethylmagnesium chloride... 

Asymmetric cross-coupling of secondary alkyl Grignard reagents represented by 1-phenylethylmagnesium chloride, which undergo racemization under the reaction conditions, produces enantiomericaUy emiched alkenes of up to 94% ee. The reaction has been studied mainly with nickel catalysts rather than palladium catalysts. 

Experimentally, a-(trimethylsilyl)benzylmagnesium chloride gives higher enantiomer excesses in asymmetric cross-coupling than does a-methylbenzyl-magnesium chloride [31], The same modelling procedure as described above... 

Plate 1 A possible sequence of intermediates involved in asymmetric cross-coupling of a-methylbenzylmagnesium chloride with p-methoxy-p-bromostyrene, showing first the oxidative addition of the halide, and then the formation of a dialkylpalladium complex with reductive elimination in the final step. The molecular models were produced in Chem3D Plus, using literature crystallographic coordinates to generate the initial complex. 

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