Benzaldehyde reactions with butyllithium

Methylthiomethyllithium was prepared by Peterson [304] from the reaction of dimethyl sulfide with the (TMEDA)-n-butyllithium complex. Subsequent reaction with benzaldehyde afforded the corresponding alcohol in an 84% yield. 

The halogen metal exchange reaction between 7-bromo or 7-iodo-3-phenyltriazolopyrimidine 165 and butyllithium in iV,N,N, N -tetra-methylethylenediamine afforded the 7-lithio compound 166, whereas a similar reaction with the 7-chloro derivative 165 (R = H) gave the ring-fission product, 5-amino-l-phenyl-l//-l,2,3-triazole-4-carbonitrile 169 (91 CPB2793). Reaction of 166 with electrophiles such as benzaldehyde and ketones gave 170 and 167 respectively, together with 7,7 -bis[3-phenyl-3//-1,2,3-triazolo[4,5-d]pyrimidine] 168 (Scheme 34). 

Recently, functionalized butyl tellurides (e.g., 159) prepared by hydrotelluration of enones 158 (Section 9.13.5.2.4), were reacted with /-butyllithium to give the functionalized alkyllithiums (e.g., 160) which were captured with benzaldehyde or transformed into functionalized alkylcyano cuprates by reaction with CuCN-2 LiCl. In both cases, the obtained organometallics reacted as expected (Scheme 93).251... 

In 1987, Sonoda and co-workers reported that the tellurium-lithium exchange reaction of l-(phenyltelluro)-2-phenylethene with -butyllithium, followed by capture with benzaldehyde, gave the corresponding allylic alcohol with retention of the double-bond configuration.243 It was observed that, depending on the length of time the reaction mixture of the aryl vinyl telluride and -butyllithium was allowed to equilibrate prior to addition of the electrophile, a complex mixtures of products could be formed (Scheme 97).256... 

In the presence of weaker bases than butyllithium or sodamide active methyl groups are still able to take part in a variety of condensation reactions with carbonyl compounds. In fact, only catalytic amounts of the proton acceptor may be needed. Thus, 2-methylimidazole reacts with benzaldehyde to form the 2-styryl compound ((187), and l,2-dimethyl-5-nitroimidazole condenses with dimethylformamide dicyclohexyl acetal to give an 86% yield... 

Chiral Modification of Achiral Organometallic Reagents. The addition of n-Butyllithium or Ethylmagne-sium Bromide to aldehydes or ketones in the presence of (—)-sparteine resulted in the formation of optically active secondary or tertiary alcohols with 20% ee or lower. Optically active acyl sulfoxides (<15% ee) were obtained by acylation of p-Tolylsulfinylmethyllithium. The asymmetric Reformatsky reaction of ethyl bromoacetate with benzaldehyde proceeds with 95% ee, in an exceptional case (eq 1). ... 

Taylor and Martin (1019, 1020) have described a new procedure for the direct introduction of alkenyl substituents into the pyrazine nucleus 2-chloropyrazine (63) with methylenetriphenylphosphorane (a Wittig reagent) (64, R = H) (from methyltriphenylphosphonium bromide and butyllithium) in 1,2-dimethoxyethane and subsequent treatment with benzaldehyde gave 2-styrylpyrazine (67, R = H). A similar reaction with propionaldehyde gave 2-(but-l -enyl)pyrazine (1020). 

Treatment of benzaldehyde oxime ether (166) with butyllithium (pentane/-10 C) demonstrates the complexity of the reaction (Scheme 32) as the desired alkoxyamine (167 R = Bu) is accompanied by other oxime-derived side products" (entry 1, Table 12). Selectivity is reagent/solvent dependent as allyl Grignard (ether)," allylzinc bromide (THF)," and butyllithium (THF)" treatment produce predominantly amine (171 R = allyl) (the Beckmann rearrangement derived product), alkoxyamine (167 R = allyl) (the oxime addition product) and ketone (169 R = Bu) (the nitrile-derived pro ct), respectively (entries 2-4, Table 12). 

Dropwise addition of butyllithium to a solution of ( )-l,3-dithiane 5,5 -dioxide (110) in pyridine-THF (1.5 1) generates an anion (111), which reacts with an aldehyde to give an adduct (112) as a 1 1 diastereomeric mixture. The reaction is extremely rapid at -78 °C, but the kinetic selectivity is moderate. In the reaction with benzaldehyde or pivalaldehyde, equilibration is attained at 0 C to give predominantly a single diastereomer in good yield (Scheme 31). ... 

Cleavage of a C —Cl and a C —O bond occurred on reaction of methyl tra i-3-(acetoxychlo-romethyl)-2,2-dimethylcyclopropanecarboxylate with sodium cyclopentadienide to give methyl tran.s-3-(cyclopenta-2,4-dienylidenemethyl)-2,2-dimethylcyclopropanecarboxylate. " Treatment of [cyclopropyl(phenylselanyl)methyl]triphenylphosphonium perchlorate with butyllithium followed by benzaldehyde resulted in cleavage of the C Se and the C-P bond and formation of a 1 1 mixture of ( /Z)-l-cyclopropyl-2-phenylethene in 76% yield.Re-... 

The anions (67c)-((i7e) are prepared by the low temperature transmetallation reactions of n-butylli-thium with the corresponding allylic tin or lead compounds. The addition of (67d) to aldehydes and ketones proceeds with C—C bond formation at either terminus. Dialkyl ketones give the a-products, while benzaldehydes and benzophenone afford the y-products. Aliphatic aldehydes, acetophenone and substituted acetophenones give both types of products. The anion (67e) is not stable in solution even at -95 °C and cannot be preformed prior to its reaction with the desired substrate (67e) may be generated by Li-Br exchange between n-butyllithium and 3,3-difluoro-3-bromopropene at -95 C. ) en this preparation is performed in the presence of chlorosilanes, aldehydes, ketones, and esters, the a-products are obtained, often in good yields (Scheme 46). Reactions of (67c) with TMS-Cl and benzaldehyde afford y-adducts, whereas those with methyl iodide, acetophenone and pentanal produce a-adducts predomi-nantly. ° Anions (67a) and (67b) give a-alkylation products wiA aliphatic halides and TMS-Cl, but afford y-adducts with iminium salts. ... 

All of the oxido ylide reactions demand the presence of at least one equivalent of lithium halide. This requirement is most easily satisfied when the starting alkylidenetriphenylphosphorane is generated by the conventional butyllithium method from phosphonium salts in THF. Thus, Maryanoff et al. (22a) treated Ph3P C4Hg Br" sequentially with butyllithium, benzaldehyde, butyllithium, and acid to give 60 (R = phenyl replace Me by propyl) con-... 

Warren showed that olefination of ketones and aldehydes, or even esters, with phosphine oxide carbanions allows some control of stereochemistry in the alkene products. Reaction with an aldehyde or ketone generates diastereomeric P-hydroxyphosphine oxide products, which can be isolated and then chromatographically separated. Reaction of 573 with n-butyllithium was followed by addition of 3,4-methylenedioxy-benzaldehyde (574, known as piperonal) to give a 9 1 mixture of 575/576, the syn and anti alcohol, respectively.514 7i,e pyre syn alcohol 575 was isolated in 75% yield by chromatography on silica gel. 

All of the reactions of fluoroaziridines described above involve ring opening, but introduction of substituents onto an intact ring is an important addition to the reaction repertoire. Paralleling oxirane chemistry (e.g., 34-36), chiral aziridine 147 was deprotonated with butyllithium at — 102°C, and the resulting anion 201 was allowed to react with a variety of electrophiles." They included aldehydes, ketones, halides, and a disulfide. Reaction with benzaldehyde, for example, afforded aziridinyl alcohol 202 with preservation of configuration in 82% yield. 

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