Methylmagnesium hydride

The reduction of methyl 6-methoxy-2-naphthyl acetate with lithium aluminium hydride in refluxing ether gives 2-(6-methoxy-2-naphthyl)ethanol, which by treatment with PBr3 in refluxing benzene is converted into 2-(6-methoxy-2-naphthyl)ethyl bromide. Further reaction with KCN in refluxing ethanol-water affords 3-(6-methoxy-2-naphthyl) propionitrile, which is finally treated with methylmagnesium iodide in refluxing ethanol. 

A photochemical preparation of a Cephalotaxus alkaloid synthon (20) has been reported (Scheme 2).10 The readily accessible maleimide (17) was iodinated with iodine and silver trifluoroacetate, in 71% yield, and the resulting compound was transformed in two steps (70% overall yield) into the methylene-pyrrolone (18) by the action of methylmagnesium iodide followed by dehydration. Irradiation of (18) afforded (19) (46% yield), which, by successive hydrogenation and reduction with lithium aluminium hydride, gave the dihydro-pyrrolo[2,l-b][3]benzazepine (20). This derivative has served as a key intermediate in the total synthesis of cephalo-taxine described previously (see Vol. 7 of these Reports). 

Methylmagnesium bromide Magnesium, bromomethyl- (8,9) (75-16-1) Diisopropylamine (8) 2-Propanamine, N-(l-methylethyl)- (9) (108-18-9) 2-Methyi-i-tetralone 1 (2H)-Naphthalenone, 3,4-dihydro-2-methyl- (8,9) (1590-08-5) Cyclopropanone ethyl hemiketal Cyclopropanol, 1-ethoxy- (8.9) (13837-45-1) Sodium hydride (8,9) (7646-69-7)... 

A single diastereoisomer is obtained in the reduction of the ketone with Lithium Aluminum Hydride as illustrated in eq 3. The addition of other nucleophiles such as methylmagnesium iodide also gives single adducts. 

In the case of base-induced elimination, the Peterson alkenation relies on the strong bond formed between silicon and oxygen, and the ready propensity for silicon to be attacked by alkoxide, to drive the reaction. In the original study by Peterson, the -silylcarbinols were prepared by the addition of (trimethylsilyl)methylmagnesium chloride to the carbonyl. The caibinols were subsequently eliminated by treatment with sodium or potassium hydride or with sulfuric acid to form the methylene derivatives in excellent yield. The Peterson reaction has proven to be of general utility in the synthesis of alkenes. ... 

Cyclopropanation of a,jS-unsaturated AT-methoxy-AT-methylamides 5 with dimethyloxo-sulfonium methanide afforded the cyclopropanecarboxamides 6 in yields far superior to those obtained with the corresponding a,/J-unsaturated ketones. In almost all cases, the trans-isomer was exclusively obtained in analogy to the cyclopropanation of the corresponding unsaturated ketones. The oxygen atom of the methoxy group on the A -methoxy-A -methyl-amide 5 was found to facilitate the reaction. The substituted amides 6 can be converted to ketones (methylmagnesium bromide), aldehydes (diisobutylaluminum hydride) and carboxylic acids (potassium rerf-butoxide/water). It is noteworthy that cyclopropanecarbaldehydes and -carboxylic acids, which are not directly accessible from the corresponding a,)8-unsaturated systems under standard cyclopropanation reactions, can be obtained indirectly by this method. 

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