Methyl Grignard reagent

Therefore one route involves the addition of a methyl Grignard reagent to a five carbon aldehyde... 

Experiments ( P nmr) using 0.8 and 2 equivalents of octyhnagnesium chloride with ethyl ben2enephosphinate indicate that the nucleophilic displacement occurs first, foHowed by proton abstraction (80). Interestingly, the order of the two steps is reversed when methyhnagnesium chloride is used (81). This reaction demonstrates the difference ia reactivity between the octyl and the methyl Grignard reagents. 

The reaction of Grignard reagents with the keto group of 5a-cholestan-3-one (7) was first described in 1937/ In a later study, Barton obtained the two epimeric tertiary alcohols (8) and (9), in a ratio of 40 60 by exposing (7) to the action of methyl Grignard reagent. 

The ratio of 1,2 and 1,4-addition products is approximately 1 1. However, addition of cuprous chloride to the methyl Grignard reagent leads to exclusive 1,4-addition in yields greater than 90%. ° With isopropyl- and /-butylmagnesium bromide, only 1,4-addition products are isolated even in the absence of cuprous chloride. ... 

An isomeric mixture of 7a-methyl- (31) and 7)5-methyl-A -3-ketones (32) is obtained by cuprous chloride-catalyzed 1,6-addition of the methyl Grignard reagent to (30). ° ... 

In some cases products of rearrangement are obtained either partially or exclusively on treatment of Grignard reagents with epoxides. Thus, reaction of the 2/ ,3/ -epoxide (14) with methyl Grignard reagent affords a mixture of two epimeric secondary A-nor alcohols (15) in 80% yield and the tertiary hydroxy compound, 2a-methyl-5a-cholestan-2/f-ol (16) in 15 % yield. ... 

Ci9 — C21 pregnenolone (addition of 1 carbon side-chain to 17-keto steroid via cyanohydrin, then 1 additional carbon via methyl Grignard reagent)... 

The reaction of 17-keto steroids with hydrogen cyanide (or acetone cyanohydrin) to form a mixture of the 17-cyano-17-hydroxy compounds, followed by dehydration and reaction with methyl Grignard reagent, is one of the earliest methods for the conversion of androstanes to pregnanes. 

Reaction of estrone methyl ether with methyl Grignard reagent followed by Birch reduction and hydrolysis of the intermediate enol ether affords the prototype orally active androgen in the 19-nor series, normethandrolone (69). ° (Note that here again the addition of the methyl group proceeded stereoselectively by approach from the least hindered side.) The preparation of the ethyl homolog starts by catalytic reduction of mestranol treatment of the intermediate, 70, under the conditions of the Birch reduction and subsequent hydrolysis of the intermediate enol ether yields norethandrolone (71). ... 

Reaction of the ester with methyl Grignard reagent completes construction of the side chain (111). Photolysis... 

Besides the addition of vinylation reagents, methyllithium and methyl Grignard reagents can react with a,/1-epoxy aldehydes in a nonchelation-controlled mode79. However, the level of diastereoselectivity is moderate. 

The low yields, which are observed among styrenyl adducts, reflect a combination of the poor reactivity of the styrene at the low temperature of the reaction. For example, the combination of t-butyl Grignard with the 2,4-bis-OBoc-benzyl alcohol 15 affords the corresponding benzopyran 50 in only 50% yield even when carried out in the presence of 5-10 equivalents of the styrene (method H, Fig. 4.27).27 Yields for substituted benzopyran styrene adducts are still lower (method G, Fig. 4.27). For example, addition of methyl lithium to 2,4-bis-OBoc-benzylaldehyde 5 followed by the addition of the dienophile and magnesium bromide affords benzopyran 51 in a paltry 27% yield. Method F is entirely ineffective in these cases, because the methyl Grignard reagent competes with the enol ether and with styrene 1,4-addition of methyl supercedes cycloaddition. 

The (Et0)4.Si could have been converted to Me4.Si with a methyl Grignard reagent if desired (16). 

A very interesting study of the reaction of methyl Grignard reagents with homoleptic imido complexes of Tc(VI) has been performed [104]. Reduction of 91 with Na in THF gave the first homoleptic Tc(VI)-imido complex [Tc2(N-Ar)6] (Ar = 2,6-dimethylphenyl) [105], Under more vigorous conditions dimerization to the second homoleptic Tc(VI)-imido complex [Tc2(N-Ar)4(/i-N-Ar)2] (94)... 

Scheme 22. Reaction of homoleptic dinuclear Tc-imido complex 94 with methyl Grignard reagent...

Next is the construction of the D ring. The TMS enol ether of compound 111 undergoes oxidation with m-CPBA, providing the C-5a trimethylsilyloxy ketone 112. Addition of methyl Grignard reagent to the ketone group and subsequent dehydration provides compound 113. Osmylation of the C=C double... 

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