Generation and Alkylation

Reagents i. PhCHjNF.t,CI. 50% aq. NaOH, BrCHjCHjBr R = COjEt. CN. COMc R = COjH. CN. COMe 

A slightly different group of catalysts that have been developed for the PTC alkylation of active methylene compounds are the 2-dialkylaminopyridinium salts 

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Reactions of carbon nucleophiles with organohalogen compounds have great diversity for the construction of now carbon-carbon bonds. The intriguing synthon, ethoxyethynylsodium, is generated and alkylated in 1-ETHOXY-1-BUTANE. Following an alkylation of propynylsodium, a vinyl halide is generated in a stereoselective manner... 

A useful alternate procedure which allows the generation and alkylation of the less stable enolate anion has been reported by Stork.This method takes advantage of the fact that the thermodynamically less stable enolate anion formed in the lithium ammonia reduction of a conjugated enone... 

The two bridgehead hydrogens Ha and Hb in the anisaldehyde dithioace-tal (130) have a large difference in their acidities, as indicated by the NMR chemical-shift difference (4.88 and 5.03 ppm). Preparation of the monocarbanion (1 BuLi in THF at -78°C) and quenching with DC1 removed only the higher field hydrogen. The carbanion can be reacted with electrophiles such as primary halides, acid halides, or aldehydes to produce (135). Carbanion generation and alkylation can be repeated on (135) to yield the disubstituted derivative (136) as shown in Scheme 44. 

Notice that in each a carbanion is generated and alkylated. Also the H2N— group is introduced as a protected amide or imide group. 

Carbanions can be generated and alkylated in a two-phase liquid-liquid system using concentrated aqueous sodium or potassium hydroxide as the base. Makosza has shown that deprotonation occurs at the interface, Fig. 5.10 [12]. 

Scheme5.34. Generation and alkylation ofa-halo organometallic compounds [187, 309, 310, 316],...

Scheme5.51. Generation and alkylation ofa-halo or a-(tosyloxy)vinyllithiurr, compounds [332, 440—442].

Not only alky] groups, but also aryl [492, 493], vinyl [494], acyl [276, 495—497], alkoxycarbonyl [498], aminocarbonyl [499-501], silyl [502-504], or phosphoryl groups [279, 280] can migrate to a vicinal carbanion (Scheme 5.68). Because some of these groups can be used to stabilize a-heteroatom-substituted carbanions by chelate formation, migration of these groups to the carbanion is a potential side reaction in the generation and alkylation of chelate-stabilized carbanions. 

Generation and alkylation or other reactions of, e.g., organic oxygen, nitrogen, or sulfur anions are efficiently carried out using PTC methodology. The kind of base and system used depends on the acidity of the precursors. Phenols are readily O-alkylated in the presence of potassium carbonate in liquid-solid systems, whereas for aliphatic alcohols use of stronger bases such as concentrated aqueous NaOH is necessary ... 

The alkylation of carbon nucleophiles by SN2-type processes is an important transformation in the synthesis of organic compounds. The generation and alkylation of such nucleophiles are described in this chapter. Alkylation and acylation of nucleophilic carbon species by other mechanisms are discussed in Chapter 2. 

FuchigamiT NY (1987) Electrolytic transformation of fluoroorganic compounds. 2. Generation and alkylation of a stable (trifluoromethyl)malonic ester enolate using an electrogenerated base. J Org Chem 52 5276-5277... 

Reactions.—If allylic chlorides are treated with strong base in the presence of a primary bromide then a -haloallyl-lithiums are both generated and alkylated in situ [equation (10)], thus avoiding self-consumption of the allyl halide exclusive a-alkylation is observed. 

Sequential addition of stabilized anions and alkyl iodides to tetracarbonyliron complexes of methyl acrylate and methyl crotonate affords products consistent with regiospecific generation and alkylation of an organoironcarbonylate anion intermediate. The tetracarbonyliron group in this example is therefore serving as a control element for effecting regiospecific introduction of two carbon-carbon bonds into an acrylate ester (Scheme 13). ... 

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