Sulfones, aryl with Grignard reagents

Tosylates and other sulfonates and sulfates couple with Grignard reagents, most often those prepared from aryl or benzylic halides.Alkyl sulfates and sulfonates generally make better substrates in reactions with Grignard reagents than the corresponding halides (10-57). The method is useful for primary and secondary R. 

Scheme 4-218. Example of an iron-catalyzed cross-coupling of aryl halides or sulfonates with Grignard reagents.

The Grignard reagents used in the reaction may be either those derived from aryl halides or those formed from alkyl halides. Phenyllithium reacted with the tosylate to give sulfones rather than azoxy compounds. 

Cyclopropyl phenyl sulfones. 3-Bromo-l-(phenylsultonyl)-l-propene (1), prepared as shown, reacts with allyl, propargyl, aryl, and benzyl Grignard reagents to give (E)-2-substituted cyclopropyl phenyl sulfones (2) in moderate to good yield. This reaction is not observed with alkyl Grignard reagents. 

It should be noted that direct substitution of sulfonate or iodide derivatives at C6 is sensitive to steric hindrance. Kishi reported a failure in the substitution of a primary tosylate by vinyl cuprate in the synthesis of mycalamides where C4 had two geminal methyl substituents. An alternate five step route was developed to introduce the vinyl substituent [119]. Direct substitution of a primary triflate by an aryl Grignard reagent is a key step in the formal synthesis of (+)-apicularen A from D-glucal [194]. Displacement of a triflate with an alkynyllithium has also been used in the total synthesis of (+)-panaxacol [195]. 

The procedure iliustrated here is representative of a generai and versatile method for the preparation of 2-substituted tetrahydrofurans and tetrahydropyrans from cyclic ether sulfones and the appropriate alkynyl, vinyl, or aryl Grignard reagent. From the examples shown in the Table and others previously reported, - a selectivity for the trans-product is observed with 6-substituted tetrahydropyrans irrespective of the initial geometry of the sulfone. This implies the presence of a common reaction intermediate such as an oxonium ion which is trapped by preferred axial bond... 

Dialkyl sulfates react analogously to sulfonic esters with aryl or benzyl Grignard reagents, giving alkylated aromatic compounds.336,337... 

Cross-coupling reactions of aryl halides and sulfonates with organolithium and Grignard reagents, the Kharasch reaction... 

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