Grignard reagents optically active

A. Intermediacy of Radicals and Pathways Leading to Radicals and to Grignard Reagent Optically Active Grignard Reagent... 

If prochiral ketones are hydrosilylated with dihydrosilanes carrying different alkyl groups R ) and the siloxane is treated with a Grignard reagent, optically active silanes are produced (7) ... 

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). 

Especially in the early steps of the synthesis of a complex molecule, there are plenty of examples in which epoxides are allowed to react with organometallic reagents. In particular, treatment of enantiomerically pure terminal epoxides with alkyl-, alkenyl-, or aryl-Grignard reagents in the presence of catalytic amounts of a copper salt, corresponding cuprates, or metal acetylides via alanate chemistry, provides a general route to optically active substituted alcohols useful as valuable building blocks in complex syntheses. 

Preparation of the appropriate optically active sulfmate ester is initially required for reaction with a Grignard or other organometallic reagent. If the method is to produce homochiral sulfoxides, the precursor sulfmate ester must be optically pure. An exception to this statement occurs if the reaction yields a partially racemic sulfoxide which can be recrystallized to complete optical purity. 

Further utility of the Andersen sulphoxides synthesis is demonstrated by the preparation of optically active unsaturated sulphoxides which were first prepared by Stirling and coworkers359 from sulphinate 276 and the appropriate vinylic Grignard reagents. Later on, Posner and Tang360 prepared in a similar way a series of ( )-l-alkenyl p-tolyl sulphoxides. Posner s group accomplished also the synthesis of (+)-(S)-2-(p-tolylsulphinyl)-2-cyclopentenone 287, which is a key compound in the chiral synthesis of various natural products361 (equation 159). 

Treatment of (—)-(S)-276 with allyl Grignard reagents gives optically active allylic sulphoxides 288. This reaction, however, involves an allylic rearrangement via transition state 289 as evidenced by Mislow and his collaborators362 (equation 160). 

C. Reactions of Phosphoric and Phosphinic Acid Derivatives.—The optically active phosphinate ester (90) has been shown to react with benzyl Grignard reagents or lithium anilide with inversion of configuration. Oxidation of... 

Alkenyl sulfoxides (42 and 43) were first prepared in optically active form by Mulvaney and Ottaviani , described in an article overlooked by most workers in the field, and a year later by Stirling and coworkers through the reaction of the appropriate vinyl Grignard reagent with sulfinate ester 19. Both groups studied the addition of nucleophiles to the carbon-carbon double bond . More recently, Posner and coworkers reported a similar synthesis of ( )-l-alkenyl sulfoxides, e.g. 44 and In the synthesis of 45,... 

Optical activity retention is observed in the course of the formation of the Grignard reagent from optically active (+)-R-l-chloro-l-phenylethane and Mg in Et20.124 Treatment of the latter with Mg in EtzO and then with Me3COD gives 88% (-F)-S-PhCHDMe in 6.2% optical yield.124... 

After quenching with DzO or Bu OD, analysis of the products from the Grignard reagents formed from PhCHXMe (X = Cl, Br, I) in the optically active solvent -(R)-2-methoxypentane leads to the conclusion that Grignard reagent formation occurs on the Mg surface within a solvent cage by a one-electron transfer mechanism.1... 

Optically active (—)-menthyltin(IV) derivatives, in which tin is directly bound to a chiral carbon atom, can be synthesized easily by the reaction of the chiral Grignard reagent (—)-menthylMgCl 58 with Me3SnCl yielding (—)-menthyltrimethyltin 5995 ... 

Reaction of Grignard reagents with optically active sulfinate esters (150) is a particularly useful route to optically active sulfoxides and occurs with 100% inversion of configuration (Andersen et al., 1964). Substitution reactions of... 

The most important and widely used approach to chiral sulfoxides is the method developed by Andersen (5) based on the reaction between the diastereomerically pure (or strongly enriched in one dia-stereomer) menthyl arenesulfinates and Grignard reagents. The first stereospecific synthesis of optically active (+H7 )-ethyl p-tolyl sulfoxide 22 was accomplished in 1962 by Andersen (75) from (-)-(iS)-menthyl p-toluenesulfmate 45 and ethylmagnesium iodide. 

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