Sec-alkyl Grignard reagents

The nickel-catalyzed asymmetric cross-coupling between sec-alkyl Grignard reagents with vinyl bromide finds many applications in the synthesis of optically and biologically active substances, e.g. a-curcumene (eq. 2) and 2-aryIpropionic acids, (anti-inflammatory drugs) (eq. 3). ... 

To obtain a measure of the versatility of the method, a series of alkyl Grignard reagents were examined (32,90). The isopropyl and sec-butyl reagents failed to generate the corresponding diphosphine disulfide with... 

Fig. 10.28. The addition of a Grignard reagent to aromatic carbonyl compounds proceeds via SET in part, which is demonstrated by the partial racemizations observed here the sec-alkyl radical that occurs as an intermediate undergoes an extremely rapid racemiza-tion. The more stable the simultaneously formed magnesium-bound ketyl radical is, the larger is the share of the racemization.

Alkanes, RH (Sec. 7.7) (Sec. 10.7) (Sec. 10.8) (Sec. 19.9) from alkenes by catalytic hydrogenation from alkyl halides by protonolysis of Grignard reagents from alkyl halides by coupling with Gilman reagents from ketones and aldehydes by Wolff-Kishner reaction... 

The Grignard reagent, we recall, has the formula RMgX, and is prepared by the reaction of metallic magnesium with the appropriate organic halide (Sec. 3.16). This halide can be alkyl (P, 2°, 3°), aJlylic, aralkyl (c.g., benzyl), or aryl (phenyl... 

Let us try to get a broader picture of the synthesis of complicated alcohols. We learned (Sec. 15.12) that they are most often prepared by the reaction of Grignard reagents with aldehydes or ketones. In this chapter we Have learned that aldehydes and ketones, as well as the alkyl halides from which the Grignard reagents are made, are themselves most often prepared from alcohols. Finally, we know that the simple alcohols are among our most readily available compounds. We have available to us, then, a synthetic route leading from simple alcohols to more complicated ones. 

An enolate anion is a nucleophile and, unlike Grignard reagents and organolithium reagents, reacts easily with the electrophilic carbon of an alkyl halide. Although both the oxygen and the carbon are nucleophilic (sec. 9.3.B), the carbon is usually the most nucleophilic site in the enolate. As with other carbon nucleophiles, such as acetylides (sec. 8.3), the electron rich carbon attacks the electrophilic carbon of the halide to form a new carbon-carbon bond, with lithium iodide (Lil) as the byproduct. 

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