Asymmetric cross-coupling bromide

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

Figure 3.47. Scope of Ni/49-catalyzed asymmetric cross-coupling of vinyl bromide with secondary alkyl Grignard reagents.

Figure 3.50. Scope of Pd/54-catalyzed asymmetric cross-coupling of vinyl bromides with a-(trimethylsilyl)benzylmagnesium bromide.

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]. 

The palladium/PPFA-catalyzed asymmetric cross-coupling of a-(trimethylsilyl)-benzylmagnesium bromide 25 has also been applied to the synthesis of optically active propargylsilane 29 (18% ee) by the use of l-bromo-2-phenylacetylene as a coupling partner (Scheme 2-18) [37]. 

The asymmetric cross-coupling was successfully applied to the synthesis of optically active allylsilanes [50,51] (Scheme 10). The reactions of a-(trimethyl-silyl)benzylmagnesium bromide (49) with vinyl bromide (4b), (E)-bromopro-pene (( )-50), and (R)-bromostyrene E)-8) in the presence of 0.5 mol % of a palladium complex coordinated with chiral ferrocenylphosphine, (R)-(S)-PPFA (10a), gave the corresponding (R)-allylsilanes (51) with 95%, 85%, and 95% ee, respectively, which were substituted with phenyl group at the chiral carbon center bonded to the siHcon atom. These allylsilanes were used for the S. ... 

The nickel-catalyzed asymmetric cross-coupling between sec-alkyl Grignard reagents with vinyl bromide finds many applications in the synthesis of optically and biologically active substances, e.g. a-curcumene (eq. 2) and 2-aryIpropionic acids, (anti-inflammatory drugs) (eq. 3). ... 

Enantioposition-selective asymmetric cross-coupling has also been successfully applied to the synthesis of axially chiral biaryl molecules (Scheme 11).155],[56] Reaction of the achiral ditriflate 52 with 2 equiv of phenyhnagnesium bromide in the presence of lithium bromide and 5 mol % of PdCl2[(5)-phephos (10b)] at -30 °C for 48 h gave an 87% yield of the monophenylation product (S)-53, which is 93% ee, and a 13% yield of diphenylation product 54. The enantiomeric purity of the monophenylation product... 

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