Grignard reagents, reaction with sulfoxides

Another useful reaction of these Diels-Alder adducts is shown in equation (54). Dihydrothiazine oxide (123) from ( . )-2,4-hexadiene can be opened with a Grignard reagent to allylic sulfoxide (124) which undergoes a stereoselective 2,3-sigmatropic rearrangement via the envelope-like transition state conformation shown, having a quasi-equatorial methyl group to afford sulfenate ester (125). Desulfurization of (125) provides E)-threo smino alcohol derivative (126) in excellent overall yield. If ( ,Z)-2,4-hexadiene is used, the E)-erythro epimer of (126) is formed cleanly. 

In all cases, the major diastereoisomer (9) is crystalline. The sulfinate esters (9a-d) undergo clean reaction with Grignard reagents to yield sulfoxides in good yield and with complete inversion of configuration at sulfur as highhghted in Scheme 2.12. 

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. 

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). 

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,... 

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... 

An alternative route to enantiomeric methyl alkyl sulfoxides (95) is based on the reaction of aliphatic Grignard reagents with the dia-... 

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