Trimethylsilylmethyl magnesium chloride

The diol function of 130 was protected as its acetonide 131 (88 %). Next, the enone function was installed by a-selenation of the enoxysilane, followed by peroxide oxidation and elimination (57 % over two steps). Finally, the unsaturated ketone 132 was homologated by 1,4-addition of trimethylsilylmethyl magnesium chloride, trapping with chlorotrimethylsilane, and reoxidation, to afford the target 117 (88 %). 

Naphthyl diethyl phosphate stirred with trimethylsilylmethyl magnesium chloride in ether containing nickel acetoacetonate at ambient temperature during 10 hours... 

Based on this methodology, syntheses of ( )-estrone methyl ether and ( )-6P-methylestra-l,3,5(10)-triene-17-one were then developed.In the estrone synthesis (Scheme 20), the aromatic component 149 was obtained in high yield from 3-methyl-4-chlorophenol. The trimethylsilylmethylene moiety was introduced in >90% yield by nickel catalyzed cross-coupling of trimethylsilylmethyl magnesium chloride and aryl chloride 148. 

Homoallyl bromide 314, prepared from readily available non-racemic ester 313, was converted to the Grignard reagent, which reacted with non-racemic epoxide, derived from D-maUc acid, to afford the alcohol 305. Ozonolysis of the alkene gave a ketone, which was converted into enol tri-flate 316. Ni-catalyzed cross coupling with trimethylsilylmethyl magnesium chloride afforded the allyl silane, which was converted into the allyl stan-nane 317. The asymmetric allylation of 313 with 317 provided 304 with a ration of 8.5 1. Methyl etherification and oxidative cleavage of exo-methylene... 

Trimethylsilyldiazomethane is obtained via the interaction of trimethylsilylmethyl-magnesium chloride and diphenyl phosphorazidate (DPPA), as shown below ... 

Preparative Methods available by a Reformatsky reaction from ethyl bromoacetate, and by reaction of trimethylsilylmethyl-magnesium chloride with ethyl chloroformate. An alternative approach requires the treatment of ethyl acetate with triph-enylmethylsodium followed by chlorotrimethylsilane The use of a nitrogen base with ethyl acetate in THF followed by reaction with chlorotrimethylsilane results in a mixture of C- and O-silylation. The use of HMPA as additive in the reaction medium increases the amount of 0-silylation to 90%. Similar methods can be used to prepare analogs. 

Peterson Alkenation. Trimethylsilylmethyllithium (1) provides an alternative to a Wittig approach for the preparation of methylene compounds from carbonyl precursors. In some cases the use of (1) is superior to the Wittig approach. Condensation of (1) with a carbonyl compound results in the formation of a 8-hydroxysilane. Elimination to the alkene can be acconqtlished by use of acidic or basic conditions (eq 1). acetyl chloride or thionyl chloride can also be used to accomplish this elimination. A wide variety of aldehydes and ketones have been used as substrates in this reaction. The use of cerium(III) chloride has been advocated with reagent (1) to favor nucleophilic addition with enolizable carbonyl corrqtounds. The use of the lithium agent (1) gives superior yields compared to the use of trimethylsilylmethyl-magnesium chloride with cerium, ... 

The copper-mediated Sn2 reaction of ( )-3-f-butyldimethyl-silyl-1-methyl-2-propenyl carbamate with trimethylsilylmethyl-magnesium chloride furnishes a-trimethylsilylmethyl-substituted (Z)-crotylsilane regio- and stereoselectively (eq 22)7 On the other hand, a similar reaction of the corresponding (Z) carbamate with trimethylsilylmethyllithium exhibits the opposite stereoselectivity (eq 23). 

When 1,3-diene is the radical acceptor, a three-component coupling reaction of alkyl halide, 1,3-diene, and trimethylsilylmethyl-magnesium chloride takes place to afford homoallylsilane The final step of the three-component coupling is reductive elimination from allyl(trimethylsilylmethyl)cobalt that predominates over conceivable /3-hydride elimination. 

Trimethylsilylmethylallenes, previously unreported, can be prepared in good yields by treatment of propargylic tosylates or acetates with trimethylsilylmethyl-magnesium chloride in the presence of copper(i) salts e.g. Scheme 102). 

Trimethylsilylmethyl Af-methylanilides (20.1) are conveniently synthesized from a nitrobenzene by successive treatments with trimethylsilyimethyl magnesium chloride at 0°C, reduction of the nitro group and yV-acylation. The anilide cyclizes in high yield at — 20°C. 

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