Grignard and Organolithium Reagents

It might be expected that strongly basic alkyllithium reagents (RLi) would deprotonate an arene (ArH) directly to form the aryllithium (ArLi) and the alkane (RH). Although this reaction does occur, it is usually extremely slow and side reactions may compete. In addition, deprotonation of most substituted benzenes will probably occur in a random manner rather than at a particular position in the benzene ring. 

Such deprotonations may be achieved with SchEosser s super base , a combinatian of butyllithium wid potassium terf-butoxide. Me,COK (Bu OK). This reagent is even more basic than organolithium species. 

The ortho substituent stabilizes the molecule by coordination to the lithium as shown in 2. This process is only possible when the lithium occupies the 2-position and so lithiation occurs exclusively at this site. Substituents that can behave in this way are known as directing metal-lation groups (DMG). The coordinating ability of a substituent varies and hence their effectiveness in directing metallation to the ortho position is variable. The process is known as directed orthometallation and is a significant development in the field of aromatic chemistry. 

Other directing groups include CONR. CH=NR, CH. NR, CsN. Cr CH[,OR),. and the heterocyclic groups 

See Chapter B fc r.tner examples of carbanions reacting with carbony compounds and a discussion of the reaction. 

Other directing groups include CONR2, CH=NR, CH NRj, C N, CFg, CH(0R)2, and the heterocyclic groups 

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These compounds are sources of the nucleophilic anion RC=C and their reaction with primary alkyl halides provides an effective synthesis of alkynes (Section 9 6) The nucleophilicity of acetylide anions is also evident m their reactions with aldehydes and ketones which are entirely analogous to those of Grignard and organolithium reagents... 

Section 15 4 Grignard and organolithium reagents react with ethylene oxide to give primary alcohols... 

Addition of Grignard and organolithium reagents to imines 2. derived from enantiomerically pure (S)-valinol (1), provides a-substituted phenethylamines 3 in moderate to good yield and excellent diastereoselectivity (in each case only one diastereomer can be detected by NMR)15. By appropriate selection of imine and organometallic reagent both diastereomeric amines are accessible (see also refs 16 and 17). 

Excellent results are achieved in the diastereoselectivc addition of Grignard and organolithium reagents to hydrazones 17 or 19 derived from either r,-ephedrine17 19 or L-valinol20. 

Decarboxylation reactions of metal carboxylates [Eq. (1)], are of increasing value in the synthesis of organometallic compounds (1-5). The reverse reaction, e.g., carbonation of Grignard and organolithium reagents (6,7), is a well-known source of carboxylic acids. Early reviews of the... 

As emphasized above, the practical utility of organocerium compounds is to circumvent the problems which are faced with the corresponding Grignard and organolithium reagents because of their inability to react effectively with sterically demanding carbonyl compounds and carbon-heteroatom unsaturated bonds which have acidic a-protons. Some of the latest examples are shown below. 

Finally, pure organocopper compounds have found applications in one-step syntheses of tri- and diorganotin halides. Its has now become well established that treatment of Grignard and organolithium reagents with tin(IV) halides always gives a mixture of products (Eqn. 1 in Scheme 1.14) rather than the desired tri- or diorganotin halides. 

Additions of both Grignard and organolithium reagents can be catalyzed by 5-10 mol % of CeCl3. 

Dimethylpyrimido[4,5-f]pyridazine-5,7-dione 23 and its derivatives undergo attack at both C-3 and C-4. Under conditions of kinetic control, addition occurs preferentially at the more electron-deficient C, whereas thermodynamic control conditions, or the use of bulkier nucleophiles, favor addition at the less hindered position 3. This duality is illustrated by the addition of Grignard and organolithium reagents to C of 3-chloro analogue 24 (Equation 9), whereas stabilized nucleophiles such as the anion of nitromethane add at C-3 (Scheme 10) <2000CHE975>. Displacement of the 3-chloride occurs also upon treatment of 24 with amines (Equation 10) <2000CHE1213>. 

These reagents add to the chiral ketones 3 with high 1,5-asymmetric induction. Grignard and organolithium reagents show slight diastereoselectivity.3 Example ... 

The addition of Grignards and organolithium reagents proceeds by attack at the metal center in ir-allylpalladium complexes. The regiochemical selectivity exhibited by these hard carbon nucleophiles with ir-allyl complexes substituted at the termini with alkyl or aryl groups is comparable to the soft carbon nucleophiles (ligand attack) in most cases, with addition occurring predominantly at the less substituted terminus (equations 248 and 249).1591387... 

A range of 2.4.4.6-tetraary 1-4//-thiopyrans has been obtained by the reaction of 3,5-disubstituted 2,4,6-triphenyl-thiopyrylium salts with aryl Grignard and organolithium reagents (Equation 122) <1996JPH(101)33, 1997PS(120)403>. 

Mechanism 14-4 Base-Catalyzed Opening of Epoxides 653 14-14 Orientation of Epoxide Ring Opening 654 14-15 Reactions of Epoxides with Grignard and Organolithium Reagents 656 14-16 Epoxy Resins The Advent of Modern Glues 656 Summary Reactions of Epoxides 658 EssentialTerms 660 Study Problems 662... 

Use Grignard and organolithium reagents for the synthesis of primary, secondary, and tertiary alcohols with the needed carbon skeletons. 

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