Nucleophilic Displacements at Carbon by Grignard Reagents

Department of Chemistry, University of Wisconsin-Milwaukee, Milwaukee, Wl 53201 

The Wurt/ coupling side reaction, which generally accompanies the formation of Grignard reagent from alkyl halide and magnesium, gives products 

2 SURVEY OF COUPLING REACTIONS OF GRIGNARI) REAGENTS WITH ORGANIC HALIDES 

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E. Alexander Hill, Nucleophilic Displacements at Carbon by Grignard Reagents, in Grignard Reagents — New Developments (H. G. Richey, Jr., Ed.), John Wiley Sons, Chichester, 2000, 27-64. 

Hill, E. A. Nucleophilic displacements at carbon by Grignard reagents, in Grignard Reagents (ed. Richey, H. G.), 27-64 (Wiley, Chichester, 2000). 

Nucleophilic Displacements at Carbon by Grignard Reagents E. Alexander Hill... 

The reaction of phenylmagnesium bromide with 1,3,2-dioxathioIane 2-oxide (16) gave 3.4-23% ethylene bromohydrin (131) and 42-60% diphenyl sulfoxide (132), depending on the conditions of the reaction. The bromohydrin (131) arises from a nucleophilic displacement at carbon by bromide ion, presumably via (129) and (130), while the sulfoxide (132) is formed by repeated attack of the Grignard reagent at sulfur (56JA454). 

A less common approach to the synthesis of phosphinates is the reaction of electrophilic phosphonates with carbon nucleophiles such as Grignard reagents or lithium enolates. For example, the phosphinic acid analogue 71 of the amino acid statine was synthesized by displacement of tert-butyl lithioacetate on a 5-phenyl phosphonothioate 70 (Scheme 23)d104l The racemic diastereomers of the 5-phenyl phosphonothioate were obtained in pure form, and the displacement of the phenylsulfanyl moiety was found to be stereospecific, although the stereocenter at phosphorus would later be lost on hydrolysis of the ester. A similar displacement reaction has been described using the p h osp h on och I ori d ate.1711... 

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