S Butyllithium

It should be noted that the sense of asymmetric induction in the lithiation/ rearrangement of aziridines 274, 276, and 279 by treatment with s-butyllithium/ (-)-sparteine is opposite to that observed for the corresponding epoxides (i.e. removal of the proton occurs at the (S)-stereocenter) [102], If one accepts the proposed model to explain the selective abstraction of the proton at the (R) -stereo-center of an epoxide (Figure 5.1), then, from the large difference in steric bulk (and Lewis basicity) between an oxygen atom and a tosyl-protected nitrogen atom, it is obvious that this model cannot be applied to the analogous aziridines. 

Related compounds have been generated from BocRNCH2SnR 3 and s-butyllithium/ CuCN which also added to conjugated ketones. Other amino-cuprates are known to give conjugate addition reactions... 

Tertiary amides 9-1, 9-2, and 9-3 are lithiated at the (3-carbon, rather than the a-carbon by s-butyllithium-TMEDA. It is estimated that the intrinsic acidity of the a-position exceeds that of the (3-position by about 9 pK units. What causes the (3-deprotonation to be kinetically preferred ... 

Hyperbranched polymers have also been prepared via living anionic polymerization. The reaction of poly(4-methylstyrene)-fo-polystyrene lithium with a small amount of divinylbenzene, afforded a star-block copolymer with 4-methylstyrene units in the periphery [200]. The methyl groups were subsequently metalated with s-butyllithium/tetramethylethylenediamine. The produced anions initiated the polymerization of a-methylstyrene (Scheme 109). From the radius of gyration to hydrodynamic radius ratio (0.96-1.1) it was concluded that the second generation polymers behaved like soft spheres. 

Several nonreductive methods for cleavage of benzyl groups have also been developed. Treatment with s-butyllithium, followed by reaction with trimethyl borate and then hydrogen peroxide, liberates the alcohol.24 The lithiated ether forms an alkyl boronate, which is oxidized as discussed in Section 4.9.2. 

The above synthetic methods for oxetane all involve formation of a new C—O bond. Cyclization by formation of a new C—C bond has been applied with compounds having benzylic or alkylic CH groups. Recent examples of this type of ring closure are the rearrangement of trans- 2,3-epoxycyclohexyl allyl ether by means of s-butyllithium and the dehydrochlorination of a-cyanobenzyl 2-chloroethyl ether with aqueous base and phase transfer catalyst (equation 86). Both reactions probably involve carbanion intermediates (76TL2115, 75MIP51300). 

In this synthesis the geometry of the acyclic double bonds is controlled through their formation as part of the thiane ring. Thiacyclohexanone (711) was converted to 4-thia-l-methylcyclohexene by reaction with methylmagnesium iodide and subsequent dehydration. Metallation of (712) with s-butyllithium and alkylation of the anion with the epoxide (713) gave a tertiary alcohol which was dehydrated to yield (714). A second alkylation of (714) with trails-4-chloro-3-methyl-2-butene 1-oxide (715) completed the carbon skeleton of the Cis juvenile hormone. Reduction of (716) with lithium in ethylamine and then desulfurization with Raney nickel led to trienol (717), a product converted previously to (718). 

Reaction of the anion prepared by deprotonation of a ketene thioacetal (799) (LDA or s-butyllithium) with a carbonyl compound has been shown to afford generally the product of y-addition (800) (80JOC2236). Mercury ion-assisted hydrolysis of the 5-hydroxy ketene thioacetal provides access to a y-lactone (801 Scheme 187). The y-selectivity of carbonyl substrates is to be contrasted with the a-selectivity generally exhibited by alkyl halides in... 

Asymmetric deprotonation of /V-(/-butoxycarbonyl)indolincs at the 2-position with s-butyllithium-(—)-sparteine has been reported.161 Results of an ab initio MO study of deprotonated 2,3-dihydrooxepin suggest that the allylic anion is 15 kcal mol 1 more stable than the vinylic anion, which is, in turn, 8 kcal mol 1 more stable than the vinyl anion of cyclohepta-l,3,5-triene.162... 

Reaction of an alkyltriphenylphosphorane in tetrahydrofuran with an aldehyde produces the oxaphosphetane B, which can be further treated with 1 eq. of. s-butyllithium to from the P-oxidophosphonium ylide C. This ylide can in turn react with another aldehyde, for instance, paraformaldehyde to give, after work-up, the trisubstituted olefin D. 

Conversion of dihydrofuran and dihydropyrrole A-triisopropylbenzenesul fonyl aziridines into alkynyl amino alcohols occurs with s-butyllithium-PMDETA (Scheme 64). A mechanism has been proposed.100... 

In 1950, Letsinger reported that carbonation of 2-lithiooctane, 15, prepared by exchange of (—)-2-iodooctane with s-butyllithium in petroleum ether at —70 °C, gave (—)-2-methyl-heptanoic acid21. However, after first warming the 2-lithiooctane solution to 0°C over 20 minutes the resulting carboxylic acid was racemic. This was the first observation that a secondary alkyllithium compound inverts much more slowly than does a primary RLi compound. 

Add 22 mL of a 1.3 M solution of s-butyllithium in cyclohexane dropwise to the terphenyl solution at -78°C, and stir at that temperature for 10 min. Replace the dropping funnel by a septum. 

Simple benzamides undergo slow deprotonation with amide bases. Stronger base systems such as s-butyllithium in tetramethylethylenediamine (TMEDA) are too nucleophilic for simple benzanudes but /V,7 -dimethyl-2,4,6-triisopropylbenzamide is deprotonated in only 5 min at -78 C, and this anion is alkylated with methyl iodide to give a 77% yield of the expected product. ... 

Preparative Methods (—)-(R)-(4-methylcyclohexylidene)methyl bromide in THF is treated with s-Butyllithium... 

Alkyl carbamates, derived from 2,2,4,4-tetramethyl-1,3-oxazo-lidine (R-CH2-OCby), are deprotonated by s-Butyllithium- —)-sparteine with differentiation between the enantiotopic protons (eq 5). The pro-S proton is removed with high stereoselectivity and reliability, and, subsequently, stereospecifically substituted by electrophiles with stereoretention to give enantiomerically enriched secondary alcohols (>95% ee) after deprotection, ... 

General Considerations. The title reagent can he sequentially alkylated a to the carbonyl group in a stereocontrolled fashion (eq 2). Lithiation of the parent hicyclic lactam with s-Butyllithium and reaction with an alkyl halide affords the monoalkylated product. The epimeric mixture is treated again with s-BuLi and a second alkyl halide to give the dialkylated hicyclic lactam. The initial epimeric mixture is used directly in the second alkylation since this step proceeds via a planar enolate. It is the second alkylation that dictates the final diastereomeric ratio. The opposite stereochemistry at C-6 can be obtained by inverting the order of electrophile addition. 

The mechanism of the deprotonation of dipole-stabilized anions has been studied in detail. It has been shown by IR spectroscopy that a preequilibrium exists between the butyllithium base and the amide or amidine, forming a coordination complex prior to deprotonadon. A recent mechanistic study has shown that, in cyclohexane solvent, this prior coordination is between the amide (or added TMEDA) and aggregated s-butyllithium, and that the effect of the coordination is to increase the reactivity of the complex. The diastereoselectivity of proton removal in chiral benzylic systems has also been examined,but since the anions invert, this selectivity is of little consequence in the alkylation step. 

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