Methylmagnesium bromide Subject

In a final consideration regarding 1,2- and 1,4-addition reactions, a,(3-unsaturated carbonyl systems can be sequentially subjected to both mechanisms. As illustrated in Scheme 7.18, if methyl vinyl ketone is treated first with dimethyllithiocuprate and then with methylmagnesium bromide, the resulting product is 2-methyl-2-pentanol. 

The sequence of reactions nicely points out the relative reactivity of carbonyl groups at positions 3, 11 and 17. Reaction of the triketone 29-2 with a controlled amount of pyrrolidine leads to the formation of the enamine from the most reactive ketone, that at C3 (30-1) (Scheme 5.30). Treatment of this intermediate with methylmagnesium bromide leads to exclusive addition to C17. Although the ketone at Cn is virtually inert to addition reactions, it is subject to reduction. Reaction of 30-2 with lithium aluminum hydride thus leads to the corresponding j8-hydroxy derivative. The enamine is then removed by acid hydrolysis (30-4). Reaction of the newly formed alcohol with /i-toluenesulfonyl... 

Baneijee et al.66 have developed an alternative synthesis of the compound (129) whose utility in synthesis of Mansonone F (120) has been reported by Suh and collaborators.65 This is described in Scheme 13. Tetralone (127) was reduced with sodium borohydride to alcohol which on alkylation with benzyl chloride produced benzyl derivative (132). Its conversion to (133) was attempted by treatment with boron tribromide in dichloromethane. C ompound (133) (characterized b y m ass s pectroscopy) was obtained in poor yield. The major product was the diol (134), whose structure was confirmed by spectral data. It indicates that the demethylation was accompanied by debenzylation. Treatment of diol (134) with triethyl orthoformate and aluminium chloride afforded aldehyde (135) which was subjected to catalytic hydrogenation to produce compound (136). It was transformed to ketone (137) by oxidation and then made to react with methylmagnesium bromide in ether. The resulting tertiary alcohol on heating with p-toluenesulfonic acid in toluene for 24 hr produced the naphthalene (129) in 78% yield. 

Scheme 13 Reduction of tetralone (127) with sodium borohydride afforded alcohol, which was benzylated to obtain the derivative (132), which on treatment with boron tribromide in dichloromethane yielded this diol (134) in major proportion. It was converted to compound (136) by treatment with triethyl orthoformate and then catalytic hydrogenation. Oxidation of (136 and on subjection of the resulting ketone with methylmagnesium bromide followed by heating with p-toluensulfonic acid in toluene produced compound (129).

Dideoxy-DL-hexoses were prepared from 137 in the following way the carbon atom chain of the substrate was extended to a seven-carbon atom chain by a low temperature Grignard reaction with methylmagnesium bromide. The product obtained, 145, was separately cis-hydroxylated (to stereoisomeric tetraols 14<) or epoxidized (to epoxides 147). Products 146 and 147 were hydrolyzed and subsequently subjected to Ruff degradation. Pairs of stereoisomeric 2,6-dideoxy-DL-hexoses could be separated by column chromatography. Essentially the same approach served for a synthesis of 2-deoxy-DL-eo f/ ra-pentose. In this case compound 138 (X = OH) was used as a substrate for epoxidation. 

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