Methylmagnesium chloride, reactions

Thiocarbonyl tetrachloride, 46, 21 m Thiocresol (Warning), 47, 107 Thionyl chloride, 46, 16 98 Thiophosgene 46, 21 Thiophosphoryl chloride, reaction with methylmagnesium bromide to i lelci tetramethylbiphosphine disulhdc 46,102... 

Methylmagnesium chloride has been added to various d-(4-substituted-phenyl) <5-oxo esters 15 (X = H, Cl 13, F, Cl, Br, OC11,) which provides the diastereomeric -lactones 1642. The electronic properties of the phenyl 4-substituent have no significant influence on the diastereoselectivity. Except for the 4-methoxyphenyl compound, which is unreactive even at 60 °C, a ratio of ca. 40 60 in favor of the anti-Cram product is observed at 60 "C in tetrahydrofuran as reaction solvent. Lowering the reaction temperature to 0 °C slightly increases the anti-Cram selectivity in the case of the 4-fluoro-, 4-chloro-, and 4-bromo-substituted compounds. On the other hand, a complete loss of reactivity is observed with the <5-phenyl- and <5-(4-methylphenyl)-substituted h-oxo esters. 

After stirring at room temperature for 1 hour, methylmagnesium chloride (1.0 M THF solution, 112mL) was added at 0°C over 30 minutes. The reaction mixture was stirred at room temperature for 1 hour. To this solution, borane-THF complex (1.0 M, 70 mL) was added at 0 °C, and the mixture was stirred at the same temperature for 1 hour. 

Thiocarbonyl tetrachloride, i6, 21 Thionyl chloride, 45, 16, 98 Thiophosgene, 45, 21 Thiophosphoryl chloride, reaction with methylmagnesium bromide to yield tetramethylbiphosphine disulfide, 45,102 Toluenesulfonybromide, 46, 88 Trichloroacetyl fluoride, 46, 6 1,1,3-Trichloiio- -nonane, 46,104 Tricyclo[2.2.1.0 ]heptan-3-ol, 45,... 

Methyltrichlorosilane is produced by the Grignard reaction of silicon tetrachloride and methylmagnesium chloride (structure 17.24). Dimethyldichlorosilane, used in the synthesis of polydimethylsiloxane, is obtained by the reaction of methylmagnesium chloride and methyltrichlorosilane (structure 17.25). 

With unsubstituted 5-iodouracil 336, a trimagnesiated species 337 can be formed by sequential treatment with methylmagnesium chloride and isopropylmagnesium chloride, and reaction with various electrophiles then selectively gives 5-functionalized uracil derivatives 338 <20070L1639>. The same procedure was also successfully applied to the functionalization of 6-iodouracils, including the synthesis of Emivirine and l-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (ElEPT) precursors <20070L1639>. 

SCHEME 17a. Reaction of methylmagnesium chloride and 2-methoxyacetaldehyde (a-1) and its extension to the chiral reaction (a-2)... 

Surprisingly, when the same authors started from a 6,8-dichloropurine derivative, the course of the reaction depended on the reagent. Phenylboronic acid showed a marked preference for the 6-position again, while the iron catalyzed coupling of methylmagnesium chloride proceeded selectively in the 8-position (8.3.), The rationale behind the observed selectivity is still unclear.8... 

Experiments (31P nmr) using 0.8 and 2 equivalents of octylmagnesium chloride with ethyl benzenephosphinate indicate that the nucleophilic displacement occurs first, followed by proton abstraction (80). Interestingly, the order of the two steps is reversed when methylmagnesium chloride is used (81). This reaction demonstrates the difference in reactivity between the octyl and the methyl Grignard reagents. 

The electrolysis of methylmagnesium chloride in THF at a three dimensional anode consisting of lead pellets is the principal reaction of the NALCO-process, which produces 18.000 tons of Pb(Me)4 per year 617 Another technical process for the preparation of Pb(Me)4 was developed by Ziegler and Lehmkuhl 618 electrolyzing NaAl(Me)4 in diglyme at a lead anode. 

Reduction of the olefinic bond in 12 and Swem oxidation of the free carbinol function provided ketone 53, onto which installation of the methyl group was performed by reaction with methylmagnesium chloride in THF. After protection of the resulting tertiary alcohol as a TBS-ether, fully protected triol 54 was obtained with a useful 80% diastereomeric excess. Acetonide deblocking and oxidative fission of the diol formed led to aldehyde 55, ready for the planned cyclization step. Exposure of aldehyde 55 to TBSOTTDIPEA reagent system smoothly resulted in formation of the desired bicyclic adducts 56 and 57 which were isolated in a 82% combined yield (60 40 ratio). 

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