Acetophenone with butyllithium

The synthesis of pyrazolines and pyrazoles of the [CCNN + C] type with the creation of two bonds, N(2)-C(3) + C(3)-C(4) (or N(l)-C(5) + C(5)-C(4)), has been studied by several groups. Beam and coworkers have published a series of papers on the synthetic utility of lithiated hydrazones. Thus, the methylhydrazone of acetophenone (598) is converted by butyllithium into the dianion (599), which in turn reacts with methyl benzoate to afford the pyrazole (600) (76SC5). In earlier publications Beam et al. have used aldehydes and acyl chlorides to obtain pyrazolines and pyrazoles by the same method. 

Carbanions derived from optically active sulfoxides react with esters, affording generally optically active )S-ketoesters ° . Kunieda and coworkers revealed that treatment of (-t-)-(R)-methyl p-tolyl sulfoxide 107 with n-butyllithium or dimethy-lamine afforded the corresponding carbanion, which upon further reaction with ethyl benzoate gave (-l-)-(R)-a-(p-tolylsulfinyl)acetophenone 108. They also found that the reaction between chiral esters of carboxylic acids (R COOR ) and a-lithio aryl methyl sulfoxides gave optically active 3-ketosulfoxides The stereoselectivity was found to be markedly influenced by the size of the R group of the esters and the optical purity reached to 70.3% when R was a t-butyl group. 

D. 2-Methyl-2-phenyl-4-pentenal (7). A dry, 100-mL three-necked, round-bottomed flask with 14/20 joints is fitted with a magnetic stirrer, reflux condenser, and a rubber septum (Note 16). The flask is charged with 50 nL of anhydrous tetrahydrofuran (Note 17) and cooled to -78°C in a dry ice/isopropyl alcohol bath, and a solution of butyllithium (12.0 mmol) in hexane (Note 18) is added with stirring. To this stirred solution is added dropwise via syringe a solution of 3.06 g (12.0 mmol) of diethyl N-benzylideneaminomethyl phosphonate (5) in 5 it of anhydrous tetrahydrofuran, and the colored solution is stirred an additional hour at -78°C. A solution containing 1.20 g (10.0 mmol) of freshly distilled acetophenone in 5 nL of anhydrous tetrahydrofuran is added dropwise, and the cooling bath is removed. The solution is stirred for 1 hr at room temperature and then at reflux for 2 hr. After the solution is cooled to room temperature, it is poured into a 250-nt round-bottomed flask and the solvents are removed under reduced pressure on a rotary evaporator. The yellow residue is partitioned between... 

It is a modification of the Shapiro olefin synthesis3 which allows the vinyl anion intermediate to be trapped with primary halides and other electrophiles. Use of triisopropylbenzenesulfonylhydrazones as the vinyllithium precursor4 is an improvement over previously4 used toluenesulfonylhy-drazones,5 6 which can be employed in the sequence provided excess sec-butyllithium (typically 4.5 equiv) and alkyl halide (3.0 equiv) are used. Methyl ketones (e.g., acetone, acetophenone, 2-octanone) can also be used and can be converted into their dianions using 2.2 equiv of the weaker base, n-butyllithium. The conditions described above, with the slight modifications noted, have been used for a variety of ketones as shown in Table I. 

Borohydride Reagent. Treatment of NB-enantrane with t-Butyllithium provides the lithium trialkylborohydride NB-Enantride (eq 4). This reagent is an effective asymmetric reducing agent for acetophenone and alkyl methyl ketones such as 2-octanone (eq 5). Few reagents show selectivity for such alkyl ketones. 

Lithiated DBU (40), prepared from DBU and -butyllithium, was reacted with benzophenone, acetophenone, benzaldehyde, phenylacetyl chloride, benzyl chloride, 1-bromopentadecane and phenyl isocyanate to give the respective 6-substituted pyrimido-[l,2-a]azepines (562-564) (86JHC885). When heated at 150 or 180°C, the hydroxy derivatives 562 decomposed and the starting ketones and DBU were recovered. 

Seyferth ef al." generated chlorocarbene from /i-butyllithium and methylene chloride in the presence of triphenylphosphine to produce triphenylphosphine chloromethyl-enc, which reacts with acetophenone to give a mixture of W.v- and rran.v-l-chloro-2-phenyl-l-prupene (2). 

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. ... 

Tiimethylsilyl)ethanesulphonyl chloride, Me3SiCH2CH2S02Cl, is useful for the protection of primary and secondary amines as sulphonamides, which are smoothly cleaved by fluoride ion. Use of the triazene moiety as a protecting group for aromatic amines is illustrated in eqnation 110. The protected compounds react with s-butyllithium, followed by an electrophile E (carbon dioxide, acetophenone or trimethylsilyl chloride), to give, respectively, the corresponding carboxyhc acid, alcohol or trimethylsilyl daivative, which are converted into the free amines by the action of nickel -aluminium alloy in aqueous-methanolic potassium hydroxide-... 

Methyl isocyanide in dry tetrahydrofuran added dropwise with stirring at -70° to butyllithium in tetrahydrofuran-hexane, after 10 min. acetophenone in tetrahydrofuran added dropwise at the same temp., and the product isolated after an additional 10 min. -> l-isocyano-2-phenyl-2-propanol. Y 1S%. F. e. s. W. A. Boll et al., Ang. Ch. 82, 482 (1970). 

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