Methylmagnesium bromide, reaction with esters

Mixtures that are already 99% (S,S)-diol (a7 )-a-chloro boronic ester on reaction with methylmagnesium bromide or other simple alkylmetallic compounds must undergo destruction of the 1 % (. >,.SJ-diol (o S)-a-chloro boronic ester to byproducts that have very different physical properties from the major product. Thus, this chemistry accounts for the very high diastereomeric ratios noted in Table 1 (Section 1.1.2.1.2.1.). 

The rather different scheme used to prepare the propionic acid side chain in cicloprofen (52-5) leads to the inclusion of this tricyclic compound in the present chapter, which is intended to deal with monocychc compounds. The synthesis starts with the Friedel-Crafts acylation of the hydrocarbon fluoiene (52-1), with the half-ester of oxalyl chloride to give the a-ketoester (52-2) as the product. The required side chain methyl group is then added by reaction of the product with methylmagnesium bromide this apparently proceeds selectively... 

Reaction of optically active seleninate ester (/ )-(—)-107 with methylmagnesium bromide gave the selenoxide (R)-(4-)-108 (Equation 19) <2005JOC5020>. 

Corey and Broger have published a very elegant synthesis of elemol (250) involving, as the key step, the nickel-carbonyl-induced cyclisation of the ester-dibromide (251). According to previous work by Corey and co-workers this reaction could have led to the formation of (252) and/or (253) in addition to other geometric and epimeric isomers. In the event, however, the major product was the elemadiene isomer (253, 7)5-C02Me) and none of the trans,trans-cyclodeca-l,5-diene (252) was formed. The ester (253) was then converted to elemol by treatment with methylmagnesium bromide. 

The synthesis begins with an Sn2 reaction (Chapter 10, Section 10.2) of bromide 141 with potassium cyanide to give 144. Note the use of the aprotic solvent DMF to facilitate the 8 2 reaction. A Grignard reaction of the nitrile with methylmagnesium bromide followed by hydrolysis leads to the requisite ketone (see Chapter 20, Section 20.9.3). The final step simply reacts the methyl ketone with LDA under kinetic control conditions to give the enolate anion (143), which is condensed with the ester (142) to give the diketone target, 140 (Section 22.7.2). 

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