Butyllithium as base

Pyridine A-oxides are readily deprotonated at C(2) using LDA or -butyllithium as base in THF and the reagents thus produced react in the usual way in high yields with a variety of electrophiles including iodine, alkyl halides, aldehydes, and ketones < 1995J(P 1 )2503>. For example, -lithio derivative 361 can be generated and intercepted by various electrophiles, e.g., carbon dioxide, elementary sulfur, or cyclohexanone giving 362 note that the lithiation prefers the carbon to the oxide rather than that ortho to the chlorine. 

The regioselectivity of the iodolactonization of l,6-hcptadicnc-4-carboxylic acid derivatives24 is strongly affected by electronic factors. In fact, the electronic control, as a consequence of the differential alkene substitution, was proven in the iodolactonization of 2-methyl-l,6-heptadi-ene-4-carboxylic acid and 2-methyl-l,6-octadiene-4-earboxylie acid. The conditions employed play an important role in the selectivity low temperature, tetrahydrofuran as solvent and butyllithium as base strongly increase the trans/cis selectivity in favor of the methallyl moiety. 

Reduction of pseudoephedrine amides with metal amide-borane complexes, and lithium amidotrihydroborate (LAB) in particular, furnishes the corresponding primary alcohols in high yield. In the initial report, LAB was prepared by deprotonation of the commercial, solid reagent borane-ammonia complex, using slightly less than 1 equiv of butyllithium as base (eq 11). In... 

One reason for the low yields in these reactions was eventually traced to the attack by butyllithium at the sulfur center in competition with deprotonation of the terminal acetylenes. By using the more hindered mesityllithium, we were able to improve the yield of the 24-mem-bered ring, mixed heterocyclic 95 from 5 ti (butyllithium as base) to 24% (mesityllithium as base) [22]. The earlier reactions outlined in Fig. 9-26 that involve deprotonation of sulfur-containing substrates by butyllithium have not been reexamined using mesityllithium as the base. 

Z-Olefins are also obtained in 95% geometrical purity if THF-HMPT (2 1) or THF-DMSO (2 1) is used as solvent. In these systems potassium can be replaced by -butyllithium as base. ... 

Because carbonyl compounds are only weakly acidic, a strong base is needed for enolate ion formation. If an alkoxide such as sodium ethoxide is used as base, deprotonation takes place only to the extent of about 0. l% because acetone is a weaker acid than ethanol (pKa - 16). If, however, a more powerful base such as sodium hydride (NaH) or lithium diisopropylamide ILiNO -CjHy ] is used, a carbonyl compound can be completely converted into its enolate ion. Lithium diisopropylamide (LDA), which is easily prepared by reaction of the strong base butyllithium with diisopropylamine, is widely used in the laboratory as a base for preparing enolate ions from carbonyl compounds. 

In the reaction of 1,3-dithiane oxide anions with iV-acylimidazoles the optimum procedure involved a sodium hexamethyldisilazide/butyllithium mixture as base [101]... 

An attempt to functionalize position 6 of the oxazolo[4,5- ]pyridine 112 was unsuccessful when using -butyllithium and an electrophile at —78°C however, successful Heck coupling was achieved using palladium(ll) acetate and tri-o-tolylphosphine in dimethylformamide (DMF) with triethylamine as base (Equation 20 Table 19) <1996TL2409, 1997T5159, 1998BMC1963>. The Stille (Equation 21 Table 20) and Suzuki couplings were also found to be successful (Equation 22). 

General methods for the preparation of a.jS-unsaturated iron-acyl complexes are deferred to Section D 1.3.4.2.5.1.1. examples of the alkylation of enolates prepared via Michael additions to ii-0 ,/ -unsaturated complexes prepared in situ are included here. Typical reaction conditions for these one-pot processes involve the presence of an excess of alkyllithium or lithium amide which first acts as base to promote elimination of alkoxide from a /f-alkoxy complex to generate the -a,)S-unsaturated complex which then suffers 1,4-nucleophilic addition by another molecule of alkyllithium or lithium amide. The resulting enolate species is then quenched with an electrophile in the usual fashion. The following table details the use of butyllithium and lithium benzylamide for these processes44,46. 

Similarly, iV-silylmethylbenzotriazole derivatives have been prepared, using in this case n-butyllithium as the base and various electrophiles including cyclohexenone. Even alkylation of RSMA-type benzotriazole derivatives can be performed, leading to a new class of SMA (R2SMA).157... 

The TOSMIC anaiog -(tosyl)benzyl isocyanide readily reacts with simple acceptors (ethyl acrylate, acrylonitrile, etc.) to give 4-substituted 2-arylpyrroles. Extension to 2,3-diaryl derivatives by use of styryl acceptors required the use of n-butyllithium as a base. <95SC795>... 

Hydrogen atoms at the 3- and 5-positions of isoxazoles are readily removed as protons. Such reactions, with nucleophilic reagents acting as bases, usually result in ring opening. When the 3- and 5-positions are blocked, deprotonation at an unsubstituted 4-position can lead to metalla-tion by, for example, n-butyllithium, as in Eqs. (19)-(21).153-155... 

Silylcyclopropanation. This ylide reacts with a,/3-unsaturated cyclohexenones and cyclopentenones to give silylcyclopropyl ketones in fair yields (35-65%). The method by which 1 is generated is extremely important for this reaction. Neither t-nor n-butyllithium can be used as base. Epoxides, which would have resulted from desilylation to dimethylsulfonium raethylide, are not formed. 

In addition to their behavior as bases, primary and secondary amines can also act as very weak acids because an N-H proton can be removed by a sufficiently strong base. We ve seen, for example, how diisopropylamine (p/Cy = 40) reacts with butyllithium to yield lithium diisopropylamide (LDA Section 22.5). Dialkylamine anions like LDA are extremely powerful bases that are often used... 

Soai et al. investigated the effects of amines on the diastereoselectivity of the conjugate addition of butyllithium to the a,j -unsaturated amide 274, derived from the a-amino acid of S-proline. When DBU was applied as base, (-)-(/ )-3-phenylheptanoic acid (275) was obtained in 55% e.e. (83SC27). 

Very often phosphonium ylides are generated with organolithium compounds (in particular phenyl-, methyl-, /j-butyl- and /-butyl-lithium) as bases.- However difficulties may be attached to this method in some cases. When alkyllithium compounds are used, ligand exchange at phosphorus may occur, thus giving rise to the alternative or additional formation of a second ylide. To avoid this phenomenon in the case of triphenylphosphonium salts phenyllithium has to be used as base. Ligand exchange may also be suppressed if one uses, instead of /j-butyllithium for example, the more bulky tertiary... 

Generation of cyclic organothio(sulfonyl)carbenes which undergo addition to nucleophilic al-kenes to give spiro-products 2, require the use of butyllithium as a base. ... 

Cyclopropyl-l,l-dihaloethenes with or without an additional halogen atom attached to C2, are generally converted to alkynes by treatment with butyllithium. The yields were generally good. The structure of the products depended on the amount of butyllithium as well as how the reaction mixture was quenched. When more than 2 equivalents of base were employed and quenching was performed with water or alcohol, the corresponding acetylenylcyclopropane was formed. ° 1 s 16,1 s 19,1820 However, when more than 2 equivalents... 

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