Sodium f-butoxide

A 250-ml flask was charged with the step 3 product (5.52 mmol), l-bromo-4-iodoben-zene (16.55 mmol), palladium dibenzanthracene (0.33 mmol), DPPF (0.66 mmol), and 80 ml toluene. The mixture stirred for 10 minutes and was then treated with sodium f-butoxide (12.14 mmol) and heated to 80°C for 4 days. It was then diluted with 1 liter of toluene and 1 liter of THF, filtered through a plug of silica and celite to remove insoluble salts, and concentrated to a brown oil. The residue was purified by flash column chromatography on silica gel using CH2Cl2/hexanes, 1 10, respectively, and 4.8 g product isolated as a yellow powder. 

Shibasaki made several improvements in the asymmetric Michael addition reaction using the previously developed BINOL-based (R)-ALB, (R)-6, and (R)-LPB, (R)-7 [1]. The former is prepared from (R)-BINOL, diisobutylaluminum hydride, and butyllithium, while the latter is from (R)-BINOL, La(Oz -Pr)3, and potassium f-butoxide. Only 0.1 mol % of (R)-6 and 0.09 mol % of potassium f-butoxide were needed to catalyze the addition of dimethyl malonate to 2-cy-clohexenone on a kilogram scale in >99% ee, when 4-A molecular sieves were added [15,16]. (R)-6 in the presence of sodium f-butoxide catalyzes the asymmetric 1,4-addition of the Horner-Wadsworth-Emmons reagent [17]. (R)-7 catalyzes the addition of nitromethane to chalcone [18]. Feringa prepared another aluminum complex from BINOL and lithium aluminum hydride and used this in the addition of nitroacetate to methyl vinyl ketone [19]. Later, Shibasaki developed a linked lanthanum reagent (R,R)-8 for the same asymmetric addition, in which two BINOLs were connected at the 3-positions with a 2-oxapropylene... 

A significant drawback of the standard conditions for palladium-catalyzed animation of aryl halides is the use of strong base. This procedure precludes the use of substrates with aromatic nitro groups, many substrates with enolizable hydrogens, substrates with esters other than /-butylesters, and substrates with base-sensitive stereochemistry, such as some protected amino acids. Thus, conditions that employ milder bases are required. A solution that involves reaction temperatures as low as those for reactions employing sodium f-butoxide has not been developed. However, carbonate and phosphate bases can be used with certain catalysts at reaction temperatures comparable to those of reactions involving the first- and second-generation catalysts. 

Compounds substituted in the 1- and 2-positions are best prepared by the series of reactions outlined in Scheme 6.22 The first step in the sequence (condensation of a hydroxyacetonaphthone with a ketone or aldehyde) gives good yields only in cases where R3 and/or R4 are not aryl.23 Condensation with a diaryl ketone (i.e., a benzophenone) can be accomplished in low yield with sodium f-butoxide in... 

Preparation of symmetrical and unsymmetfical aliphatic ethers can be accomplished by coupling alkyl halides and sodium alkoxides (H illiamson). The formation of the alkoxide may be slow and incomplete because the slow-dissolving alkoxide coats the sodium. This difficulty can be overcome by using a large excess of alcohol. After the sodium has dissolved, the alkyl halide is added to form the ether which is finally removed by fractional distillation. Sodium f-butoxide is not only formed slowly but also reacts very slowly with alkyl halides. The reaction of the f-alkyl halide with the sodium alcoholate is not any better, for the chief products are olefins. Consequently, another method must be considered for preparing f-alkyl ethers (method 118). Even in the conversion of s-alkyl halides, olefin formation occurs. 

Silver trifluoroacetate, 327, 328 Silyl ethers, 477-478 Simmons-Smith reagent, 436-437 (3-Sinensal, 283 Sirenin, 424 Sodium, 246, 268, 437 Sodium acetate, 578 Sodium aluminum chloride, 438 Sodium aluminum diethyl dihydride, 438 Sodium aluminum hydride, 316 Sodium amalgam, 41,438-439 Sodium amide, 231, 305,403,439 Sodium amide-Sodium f-butoxide, 439-440 Sodium-Ammonia, 26, 32,134, 260,438 Sodium azide, 9, 77, 210, 323, 440-441 Sodium benzoxide, 111 Sodium bis-(2-methoxyethoxy)aluminum hydride, 164, 293, 360,441-442 Sodium bistrimethylsilylamide, 442-443,... 

Triethylene glycol ditosylate (2) f-Butanol [FLAMMABLE] Sodium f-butoxide [CORROSIVE ... 

Under an inert atmosphere, prepare a solution of /-butanol (250 mL), sodium f-butoxide (20.0 g, 0.21 mol) and diethanolamine (17.0 mL, 18.9 g, 0.09 mol). Stir at 40 °C in a 1 L three-necked round-bottomed flask, fitted with a pressure-equalized addition funnel and a thermometer, for 30 min. Add a solution of triethylene glycol ditosylate, 2, (40.0 g, 0.9 mol) in dry 1,4-dioxane (150 mL) dropwise over 2h from the addition funnel. During the addition the reaction appears to be slightly exothermic and holds 40 °C with minimal external heating. Once all the ditosylate has been added continue to stir for a further 1 h and allow the solution to cool to room temperature. 

The original Thorpe conditions involved a catalytic amount of base, as the mechanism would imply. Later workers found that in certain reactions equivalent amounts of base were required or that catalytic and equivalent amounts of base gave different products. As shown in Scheme 84, the Michael dimer (177) is the major product when adiponitrile (175) is cyclized with a trace of sodium f-butoxide in f-butyl alcohol, whereas an equivalent of this base in toluene gave the monomer (176). 

Organometallic cross-coupling reactions provide a regiocontrolled method for the introduction of substituents to the indole ring. Palladium-catalzyed cross-coupling of 2-indolyldimethylsilanols have been utilized in the synthesis of 2-arylindoles <04OL3649>. For example, treatment of indole-2-silanol 206 and aryl iodides 207 with a palladium catalyst, copper iodide, and sodium f-butoxide provided 2-arylindoles 208. 

INDOLES Phenylhydrazine. Sodium amide-Sodium f-butoxide. 

Both sodium t-butoxide and potassium hexamethyldisilazide were used in palladium-catalyzed ketone arylations. While reactions involving electron-neutral or electron-rich aryl halides were more selective for monoarylation when JCHMDS was used, sodium f-butoxide gave good selectivity with electron-poor aryl halides, without direct decomposition of the aryl halide. Bis(diph-enylphosphino)ferrocene-ligated palladium complexes were... 

Fig. 6.18. The hexameric and nonameric aggregates of sodium f-butoxide, 186 (Reproduced from...

Sodium f-butoxide promotes reaction of isobutyrophenone, Ph-C(=0)-CHMe2, with an excess of benzaldehyde (>4mol), to give flnri-l,3-dibenzoyloxy-2,2-dimethyl-1,3-diphenylpropane (70). This easy access to a useful C2-symmetric chiral 1,3-diol 0 occurs via sequenbal aldol-Tishchenko and Tishchenko reactions. 

Anionic polymerization of bismaleimides can be achieved with butyl lithium at 40°C or with sodium f-butoxide at 20°C. Alkali tertiary butoxides have been used as anionic initiators at temperatures as low as -72°C [5]. 

The cyclization of 2-bromobezhydrazones 66 in PEG 400 in the presence of copper powder and sodium f-butoxide afforded 1-arylindazoles 67 (Scheme 36) [60]. 6-Aza-analogue (67, X = N, = H, Ar = Ph) was also prepared with... 

Buchwald and coworkers also disclosed a protocol for an enantioselective inter-molecular arylation and vinylation of racemic oxindoles 152 under palladium catalysis. Various aryl bromides but also 1-bromoalkenes were shown to react under the usual basic conditions maintained by an excess of sodium f-butoxide. It turned out that only axially chiral monophosphine ligands like 144b led to significant enantioselectivity. However, arylated products 154 were obtained in very high enantiomeric excess with the axially chiral and / -stereogenic ligand 153 (Scheme 5.50) [73]. 

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