Grignard reagents, asymmetric,

Asymmetric synthesis by the catalytic cross-coupling reaction has been studied most extensively with secondary alkyl Grignard reagents. Asymmetric cross-coupling with... 

With a racemic mixture of the secondary Grignard reagent, asymmetric cross-coupling with chiral catalysts creates a stereogenic center on the nucleophile. Using (iS,S)-chiraphos as ligand, the facile interconversion between the two enantiomers of a-phenethylmagnesium bromide allows the formation of the allylated product in 87% yield and 58% ee by a dynamic kinetic asymmetric transformation (Eq. 8E.28) [207]. 

The asymmetric addition of naphthyl Grignard reagents to l-methoxy-2-... 

Direct addition of Grignard reagents to Zincke-derived chiral pyridinium salts such as 99, meanwhile, allowed subsequent reduction to 1,2,3,6-tetrahydropyridines (e.g., 100, Scheme 8.4.32). This strategy provided entry to asymmetric syntheses of (-)-lupetidin and (+)-solenopsin. Tetrahydropyridines prepared by reduction of chiral... 

The carbonyl carbon of an unsymmetrical ketone is a prochiral center reaction with a Grignard reagent 2 (R 7 R, R") can take place on either face of the carbonyl group with equal chance. The products 8a and 8b are consequently formed in equal amounts as racemic mixture, as long as no asymmetric induction becomes effective ... 

Enantiomerically pure alkylboranes arc known to be excellent reagents for asymmetric reduction but they can also be used to generate enantiomerically pure /V-borylimines by partial reduction of nitriles. Addition of organolithium and Grignard reagents to these compounds affords secondary carbinamines in moderate to good yield but low enantioselectivity13,14. The best results reported so far are shown below. 

Substantially high diastereoselectivity was accomplished by the conjugate addition of Grignard reagents to the amide 1 derived from 1-ephedrine32. The reagent attacked from the Re-face of the double bond, as shown in 2, via a chelated intermediate. Low asymmetric induction was observed when butyllithium was used instead of butylmagnesium bromide. 

Geranyltrimethylsilane, 142 Grignard cross-coupling, asymmetric, 31 Grignard reaction, 39,63 Grignard reagent, 45,58,120,121... 

Simple 1,2,4-triazole derivatives played a key role in both the synthesis of functionalized triazoles and in asymmetric synthesis. l-(a-Aminomethyl)-1,2,4-triazoles 4 could be converted into 5 by treatment with enol ethers <96SC357>. The novel C2-symmetric triazole-containing chiral auxiliary (S,S)-4-amino-3,5-bis(l-hydroxyethyl)-l,2,4-triazole, SAT, (6) was prepared firmn (S)-lactic acid and hydrazine hydrate <96TA1621>. This chiral auxiliary was employed to mediate the diastereoselective 1,2-addition of Grignard reagents to the C=N bond of hydrazones. The diastereoselective-alkylation of enolates derived from ethyl ester 7 was mediated by a related auxiliary <96TA1631>. 

Scheme 23 Double asymmetric induction in the addition of Grignard reagents to chiral a-amino imines and a-amino iminium ions...

Mikolajczyk and coworkers have summarized other methods which lead to the desired sulfmate esters These are asymmetric oxidation of sulfenamides, kinetic resolution of racemic sulfmates in transesterification with chiral alcohols, kinetic resolution of racemic sulfinates upon treatment with chiral Grignard reagents, optical resolution via cyclodextrin complexes, and esterification of sulfinyl chlorides with chiral alcohols in the presence of optically active amines. None of these methods is very satisfactory since the esters produced are of low enantiomeric purity. However, the reaction of dialkyl sulfites (33) with t-butylmagnesium chloride in the presence of quinine gave the corresponding methyl, ethyl, n-propyl, isopropyl and n-butyl 2,2-dimethylpropane-l-yl sulfinates (34) of 43 to 73% enantiomeric purity in 50 to 84% yield. This made available sulfinate esters for the synthesis of t-butyl sulfoxides (35). 

In 1999, Ikeda et al. reported a new type of sulfur-oxazoline ligands with an axis-fixed or -unfixed biphenyl backbone prepared in good yields by coupling reactions of methoxybenzene derivatives substituted with a chiral oxazoline and a sulfur-containing Grignard reagent. These ligands were subsequently evaluated for the test palladium-catalysed asymmetric allylic alkylation... 

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