Pentan alkyl halides from

Organolithium compounds are sometimes prepared in hydrocarbon solvents such as pentane and hexane, but nonnally diethyl ether is used. It is especially important that the solvent be anhydrous. Even trace amounts of water or alcohols react with lithium to form insoluble lithium hydroxide or lithium alkoxides that coat the surface of the metal and prevent it from reacting with the alkyl halide. Furthennore, organolithium reagents are strong bases and react rapidly with even weak proton sources to fonn hydrocarbons. We shall discuss this property of organolithium reagents in Section 14.5. 

The result of the retrosynthetic analysis of rac-lO is 2-hydroxyphenazine (9) and the terpenoid unit rac-23, which may be linked by ether formation [29]. The rac-23 component can be dissected into the alkyl halide rac-24 and the (E)-vinyl halide 25. A Pd(0)-catalyzed sp -sp coupling reaction is meant to ensure both the reaction of rac-24 and 25 and the ( )-geometry of the C-6, C-7 double bond. Following Negishi, 25 is accessible via carboalumination from alkyne 27, which might be traced back to (E,E)-farnesyl acetone (28). The idea was to produce 9 in accordance with one of the methods reported in the literature, and to obtain rac-24 in a few steps from symmetrical 3-methyl-pentane-1,5-diol (26) by selective functionalization of either of the two hydroxyl groups. 

Generally, smaller particles are obtained with polar, more highly solvating solvents. However, these solvents do not necessarily yield the most active metal slurries. The reactivities vary, and the metal slurries can be fine tuned somewhat for use in specific types of reactions. For example, nickel particles from pentane are very active as hydrogenation catalysts, whereas nickel particles from THF are not active as hydrogenation catalysts but are very active in alkyl halide reactions. 

The metalated hydrazones are alkylated by alkyl halides, dialkyl sulfates or alkyl sulfonates at low temperatures in tetrahydrofuran (—95°C) or diethyl ether (— 110°C) to form the a-sub-stituted hydrazones in nearly quantitative yields. The ambident azaenolates react exclusively at the C-terminus side products resulting from N-, di-, or polyalkylation are not observed. The crude alkylated hydrazones can be purified by distillation or silica gel chromatography (diethyl ether/pentane) without epimerization. However, in most cases, they are pure enough to be directly cleaved to the desired alkylated carbonyl compound. 

A solution of 1 equiv of (S)- or (/ )-2-methoxymetliyl-1-[(2,2-dimethyl-l,3-dioxan-5-ylidene)amino]pyrro-lidine in THF (4 mL/mmol) is cooled to — 78 °C. 1.1 Equiv of tert-butyllithium in hexane (1.7 M) are added dropwise and the mixture is stirred for 2 h at — 78 °C. The solution of the metalated hydrazone is cooled to — 100 CC, 1.2 equiv of the alkyl halide (neat or as a solution in anhyd THF) are added dropwise, and the mixture is stirred for 1 h at —100 °C and then warmed slowly to r.t. (about 15 h). Finally, diethyl ether (30 mL/mmol) is added and the mixture is washed with pH 7 buffer (3 mL/mmol) and two 3-mL portions of brine, dried over MgSO and evaporated under reduced pressure. The Crude product is heated to 50 C for a short time if necessary (about 15 min for isomerization from the Z- to the L-isotiler monitored by TLC) and purified by silica gel column chromatography (diethyl ether/ pentane, 1 1 -2 5 Rf - > RfZ-iso-mer) to give a colorless or pale yellow product. See Table 2 for physical data. 

Seebach and Naef1961 generated chiral enolates with asymmetric induction from a-heterosubstituted carboxylic acids. Reactions of these enolates with alkyl halides were found to be highly diastereoselective. Thus, the overall enantioselective a-alkyla-tion of chiral, non-racemic a-heterosubstituted carboxylic acids was realized. No external chiral auxiliary was necessary in order to produce the a-alkylated target molecules. Thus, (S)-proline was refluxed in a pentane solution of pivalaldehyde in the presence of an acid catalyst, with azeotropic removal of water. (197) was isolated as a single diastereomer by distillation. The enolate generated from (197) was allylated and produced (198) with ad.s. value >98 %. The substitution (197) ->(198) probably takes place with retention of configuration 196>. 

Aikyl fluorides by exchange from alkyl halides or methanesulfonates. The resin used for the reaction is the F form of Amberlyst-A26 (Rohm and Haas), a macroreticular anion-exchange resin containing ammonium groups. When this material and primary alkyl halides or sulfonates are refluxed in a solvent (pentane, hexane, ether), alkyl fluorides are formed, usually in satisfactory yields. Alkenes accompany fluorides in the reaction of secondary substrates. This reaction has been conducted previously under phase-transfer catalysis (5, 322). ... 

The dioxolane, which is crystalline and easily purified, is then exchanged for the acetal derived from pentan-3-one, ready for a reduction to the rather challenging hindered ether (direct alkylation with a hindered alkyl halide would struggle to avoid competing E2 elimination). 

The reactions of bare Fe" " ions and related species in the gas phase continue to attract much interest. The remote functionalisation of 1,6-hexanediol by Fe occurs by C-H activation at C(3) and C(4).26 Functionalisation of 3-methyl-2-pentanone at C(4) is diastereoselective, probably because of the conformation of a chair-like intermediate. Reactions of Fe with anisoles and phenols have also been studied.28 Interaction of Fe with silanes gives both silene and silylene species, though the two are not interconvertible. The reactions of Fe(alkene)+ complexes with pentane were found to differ dramatically from those of bare Fe" , and C-H and C-C activation were also observed in reactions of Fe(C2H4) with oxygen. 0,31 interaction of Fe(benzyne)+ with alkyl halides led to C-X or C-C addition followed by p-elimination and loss of HX.32 The gas phase reaction of Fe(NH2)Me" with C2H4 is best explained by insertion into the Fe-C bond followed by P-elimination and loss of propene. The reaction of FeMe with 1-octyne also leads to C-C bond forming processes. 

The interest of chemists in this topic originated in two findings reported more than a century ago that exposed the influence of solvents on the rate of esterification of acetic acid by ethanol, estabhshed in 1862 by Berthelot and Saint-Gilles, and on the rate of qua-temization of tertiary amines by alkyl halides, discovered in 1890 by Menschutkin. In his study, Menschutkin found that even so-called inert solvents had strong effects on the reaction rate and that the rate increased by a factor about 700 from hexane to acetophenone. Subsequent kinetic studies have revealed even higher sensitivity of the reaction rate to the solvent. Thus, the solvolysis rate of tert-butyl chloride increases 340,000 times from pure ethanol to a 50 50 v/v mixture of this alcohol and water," and by a factor of 2.88x10 " from pentane to water. Also, the decaiboxylation rate of 6-nitrobenzisoxazol 3-carboxylate increases by a factor of 9.5x10 from water to HMPT. ... 

Grignard reagent was generated by the reaction of Mg (0.35 g 14.4 mmol) with the alkyl or aryl halide in EtjO (25 mL). Bicyclic JV,0-acetal (5.0 mmol) was added and the mixture was heated for 12 h. Then excess Grignard reagent was destroyed by addition of HjO (50 mL). The crude product was obtained by extraction of the aqueous layer with EtjO (3 x 30 mL). Evaporation of the solvent and distillation in a Kugelrohr apparatus or recrystallization from pentane gave pure products. 

The necessity of using a hydrocarbon as the solvent in the reactions discussed thus far raised the problem of using a home-made lithium reagent, since these derivatives are best made from a halogen/lithiiun exchange in an ethereal solvent. This difficulty may be circumvented if pentane, hexane, or cumene is added to the RLi,LiX reagent, prepared in ether, but a larger amoimt of sparteine has to be added, since the diamine coordinates efficiently with the lithiiun halide. The best way is to start from an alkyl chloride, so that liCl already precipitates in ether, and to piunp off this solvent after the addition of ciunene under these conditions, a 1 1 ratio of sparteine Rli can be used [27]. 

Further (c/. Vol. 1, p. 89) Russian work on fluoroalkenylcarbaboranes has been reported (see p. 60), fluoroalkylborates have been synthesized via reaction of hexafluoroacetone and related ketones with boron halides, organoboron halides, or alkylthioboranes (see p. 257), and from perfluoro-alkyl hypochlorites (see p. 264), CFj-S—B compounds have been prepared (see p. 270), and conductivity studies on the complex acid HBfOaC CFj) and its caesium salt have been described. Attempts to isolate the tristri-fluoroacetate B(02C CF3)a from products of the reaction systems B(OH)3-(CFs CO) , BCl3-(CF9 CO)jO-n-pentane, and BCl3-CF3-C02H-n-pentane have yielded only I(CF3 C0s)2B]20 or [(CF3 C02)2B]30-B(02C CF3)3 mixtures (c/. ref. 58). 

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