Pyridine-n-Butyllithium

REDUCTION, REAGENTS Bis(N-methylpi-perazinyl)aluminum hydride. Borane-Di-methyl sulfide. Borane-Tetrahydrofurane. Borane-Pyridine. n-Butyllithium-Diisobu-tylaluminum hydride. Calcium-Amines. Diisobutylaluminum hydride. 8-Hydroxy-quinolinedihydroboronite. Lithium aluminum hydride. Lithium 9-boratabicy-clo[3.3.1]nonane. Lithium n-butyldiisopro-pylaluminum hydride. Lithium tri-j c-butylborohydride. Lithium triethylborohy-dride. Monochloroalane. Nickel boride. 2-Phenylbenzothiazoline. Potassium 9-(2,3-dimethyl-2-butoxy)-9-boratabicy-clo[3.3.1]nonane. Raney nickel. Sodium bis(2-methoxyethoxy)aluminum hydride. Sodium borohydride. Sodium borohy-dride-Nickel chloride. Sodium borohy-dride-Praeseodymium chloride. So-dium(dimethylamino)borohydride. Sodium hydrogen telluride. Thexyl chloroborane-Dimethyl sulfide. Tri-n-butylphosphine-Diphenyl disulfide. Tri-n-butyltin hydride. Zinc-l,2-Dibromoethane. Zinc borohydride. 

Reducing agents Aluminum hydride. Bis-3-methyl-2-butylborane. n-Butyllithium-Pyridine. Calcium borohydride. Chloroiridic acid. Chromous acetate. Chromous chloride. Chromous sulfate. Copper chromite. Diborane. Diborane-Boron trifluoride. Diborane-Sodium borohydride. Diethyl phosphonate. Diimide. Diisobutylaluminum hydride. Dimethyl sulfide. Hexamethylphosphorous triamide. Iridium tetrachloride. Lead. Lithium alkyla-mines. Lithium aluminum hydride. Lithium aluminum hydride-Aluminum chloride. Lithium-Ammonia. Lithium diisobutylmethylaluminum hydride. Lithium-Diphenyl. Lithium ethylenediamine. Lithium-Hexamethylphosphoric triamide. Lithium hydride. Lithium triethoxyaluminum hydride. Lithium tri-/-butoxyaluminum hydride. Nickel-aluminum alloy. Pyridine-n-Butyllithium. Sodium amalgam. Sodium-Ammonia. Sodium borohydride. Sodium borohydride-BFs, see DDQ. Sodium dihydrobis-(2-methoxyethoxy) aluminate. Sodium hydrosulflte. Sodium telluride. Stannous chloride. Tin-HBr. Tri-n-butyltin hydride. Trimethyl phosphite, see Dinitrogen tetroxide. 

The utility of a-silyl- and a-stannyl-substituted crotyl-9-BBN [4] has been extended to realize the stereoregulated synthesis of four [8a] carbon units (Table 6.26). Consequently, the reaction of a-silyl- or -stannyl-substituted cro-tyl-9-BBN with aldehydes in the presence of certain bases (such as pyridine, n-butyllithium, or sec-butyllithium) provides the high regulation of the stereochemistries over four consecutive acylic carbon atoms the threo relation between C-1 and C-2 and the ds-configuration at C-3 and C-4 (Scheme 16.28) [8aj. 

Synthesis and Spectroscopic Characterization. 3-(Methyldichlorosilyl)-pyridine (1) was synthesized by the reaction of 3-lithiopyridine, prepared in situ from 3-bromopyridine and n-butyllithium, with a large excess of methyltrichlorosilane at -76° (Scheme 2). The product is a colorless distillable liquid which is soluble in aromatic, aliphatic and chlorinated hydrocarbons and extremely sensitive to moisture and protonic solvents. 

The synthesis of the representative compound of this series, 1,4-dihydro-l-ethyl-6-fluoro (or 6-H)-4-oxo-7-(piperazin-l-yl)thieno[2/,3/ 4,5]thieno[3,2-b]pyridine-3-carboxylic acid (81), follows the same procedure as that utilized for compound 76. Namely, the 3-thienylacrylic acid (77) reacts with thionyl chloride to form the thieno Sjthiophene -carboxyl chloride (78). Reaction of this compound with monomethyl malonate and n-butyllithium gives rise to the acetoacetate derivative (79). Transformation of compound 79 to the thieno[2 3f 4,5]thieno[3,2-b]pyhdone-3-carboxy ic acid derivative (80) proceeds in three steps in the same manner as that shown for compound 75 in Scheme 15. Complexation of compound 75 with boron trifluoride etherate, followed by reaction with piperazine and decomplexation, results in the formation of the target compound (81), as shown in Scheme 16. The 6-desfluoro derivative of 81 does not show antibacterial activity in vitro. 

Lithiation of thiazolo[5,4-b]pyridine-N-oxides (503) by n-butyllithium at -65°C is selectively directed by the pyridine N-oxide moiety, whereas lithiation of the parent heterocycle by LDA at -78°C exclusively occurs at the C-4 position (89TL183). Interestingly, no metalation of the furan ring occurred (Scheme 152). 

Ring metallation generally succeeds with /V-oxides. a-Lithio derivatives (348) can be generated in non-protic conditions by treating pyridine 1-oxides with n-butyllithium. These may be intercepted by various electrophiles such as cyclohexanone (Scheme 35). Reaction of substituted lithio /V-oxides with carbon dioxide gives carboxylic acids with elementary 02 and S8 (347, X = 0, S) are produced. 

With 2,4-dimethyl-pyridine and -quinoline, selective alkylation or acylation may be achieved at either position. n-Butyllithium promotes ionization at the 2-methyl groups, whereas lithium diisopropylamide reacts at the 4-methyl group. 

Ethyl pyridine-2-acetates and ethyl 6-methylpyridine-2-acetate have previously been prepared by carboxylation of the lithio derivatives of a-picoline and lutidine, respectively. Use of ethyl carbonate to acylate the organometallic derivative avoids the intermediacy of the (unstable) carboxylic acid, and the yields are better. In the present procedure potassium amide is used as the metalating agent the submitters report that the same esters may be formed by metalation with sodium amide (43% yield) or with n-butyllithium (39% yield). The latter conditions also yield an appreciable amount of the acid (which decarboxylates). 

Undheim and Riege267 obtained 1 1 adducts from pyridine-2-thiones (60) and acetylenic amides, esters, and ketones. The reaction rate increases with increase in activation of the acetylenic bond by the adjacent carbonyl group and is affected by the pyridine 6-substituent, which may also affect the stereochemical course. Product-isomer ratios corresponding to kinetic control were obtained in chloroform. Amides gave E isomers, ketones gave Z, and esters a slight preponderance of the E isomers (61). Successive addition of n-butyllithium and DMAD to... 

An improved route to the key intermediate 326 was also developed (165). Namely, 322 was converted to the monoprotected 1,4-dione 327 by sequential addition of the Grignard reagent derived from 2-(2-bromoethyl)-2-methyl-l,3-dioxolane followed by oxidation of the resulting benzylic alcohol with pyridin-ium dichromate (PDC). The ketone 327 was then smoothly transformed to the 2-azadiene 328 by olefination with BAMP. The regioselective addition of n-butyllithium to 328 as before followed by alkylation of the resulting metalloenamine with benzyl A-(2-bromoethyl)-A-methylcarbamate and acid-catalyzed hydrolysis furnished 325, which was converted to the cyclohexenone 326 by base-induced cycloaldolization and dehydration. 

Similarly to the analogous reaction with furo[2,3-Z>]pyridines, metallation of compound (20) with n-butyllithium in TMEDA followed by the addition of DMF afforded the 2-formyl derivative in 66% yield. Likewise, metallation of the isomer (22) under the same conditions afforded the 2-formyl derivative in comparable yield <84JHC785>. Introduction of a carbonyl group at C-3 of compound (20) was accomplished by halogen-metal exchange between 3-bromothieno[2,3-6]pyridine and n-butyllithium. Table 45 lists some of the thieno[2,3-Z>]pyridine derivatives formed by this method <74JHC355>. 

Nitrosation at the 5-position of 3-methoxy-4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine (237) has been used as a method to block this basic nitrogen in the synthesis of compound (242) (Scheme 23), a conformationally restricted 7V-methyl-(/ )-aspartic acid analogue, for evaluation as a potential excitor of neurotransmitters in the mammalian central nervous system <82Mi 708-02, 86ACS(B)92>. Lithiation of the derivative (238) with n-butyllithium regiospecifically at the 4-position followed by C-alkylation with the addition of methyl chloroformate gave the 4-methoxycarbonyl derivative (239), albeit in a low 16% yield. The remainder of the synthetic sequence involves a stepwise deprotection sequence (239)-(242). 

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