Reduction with zinc/copper couple

Ethynylallenes [35], the didehydro analogs of vinylallenes, have also been known for some time, the parent system 7 having been obtained in 1960 by reduction of 3-chloro-l,4-pentadiyne (101) with zinc-copper couple in butanol [36] and the 5-methyl derivative 103 by base-catalyzed isomerization of 1,4-hexadiyne (102) with sodium ethoxide in ethanol (Scheme 5.13) [9]. 

Acyloin-type reactions of esters provide the simplest route to 1-siloxy-l-alkoxycyclopropane [21,22] Eq. (6). The reaction of commercial 3-halopropionate with sodium (or lithium) in refluxing ether in the presence of Me3SiCl can easily be carried out on a one mole scale [21]. Cyclization of optically pure methyl 3-bromo-2-methylpropionate [23], available in both R and S form, gives a cyclopropane, which is enantiomerically pure at C-2, yet is a 1 1 diastereo-meric mixture with respect to its relative configuration at C-l Eq. (7). Reductive silylation of allyl 3-iodopropionate with zinc/copper couple provides a milder alternative to the alkali metal reduction [24] Eq. (8). 

A very practical route to zinc homoenolate involves reduction of 3-iodoesters with zinc/copper couple in the presence of a polar solvent, e.g. DMF, DMA [49] Eq. (51). The nature of the species obtained in this approach is not well-defined, but appears to be essentially the same as the one obtained along the siloxycyclo-propane route. Acylation, arylation, and vinylation reactions have been reported. 

Diketo diester 512 has played a key role in one of Paquette s approaches to the pentagonal dodecahedrane. Direct hydroboration-oxidation of502 provided as the principal product the unwanted isomer 511 (49 %) rather than 512 (30 %). This complication was circumvented by the improvisation of the cross-corner oxygenation sequence outlined in Scheme 75.420,42 The iodolactonization of diacid 510 proceeded with high efficiency to give 513 which underwent cleavage to 514 in the presence of methanolic sodium methoxide at room temperature. Oxidation to a-iodo ketone 515 followed by reductive deiodination with zinc-copper couple and ammonium chloride in methanol solution furnished isomerically pure 512. 

The chloro nitroso adducts of the ( -protected glycals were converted, via the intermediate oximes, to 2-amino-2-deoxy sugars48,50,53,59 the overall oxyamination of glycals is hence accomplished. Amines of the opposite configuration are prepared depending on the method of reduction. The chloro nitroso adducts can be directly treated with zinc-copper couple in acetic acid, or can be first converted to fully acetylated oximes which are then catalytically hydrogenated. 

Synthesis of allenes. A report by Ginzburg5 that reduction of dimethylethynyl-carbinyl chloride (5) with zinc-copper couple in ethanol affords 3-methyl-1,2-... 

Alternatively, reductive dehydroxylation of 326 with zinc-copper couple followed by N-acetylation and debenzylation with lithium in liquid ammonia affords 328. Ruthenium dioxide-sodium periodate oxidative cleavage of the furyl ring and conversion to the methyl ester with diazomethane affords the (R)-a-amino acid ester 329, which is a fully protected a-epimeric jS-alkoxy-a-amino acid [114]. 

Preparative Methods several methods for the preparation of bis[(trimethylsilyl)methyl]zinc have been reported. Addition of powdered anhydrous zinc(II) chloride to a solution of [(trimethylsilyl)methyl]magnesium chloride in diethyl ether at 0 °C and subsequent stirring for 4 days at room temperature affords the title compound in 90% yield after fractional distillation. A second route consists of the reaction of (iodomethyl)tri-methylsilane with zinc/copper couple (prepared by reduction of CuO with dihydrogen in the presence of zinc dust) at reflux for 3 h and affords the title compound in 56% yield. Bis[(trimethylsilyl)methyl]zinc can also be prepared quantitatively by reacting bis[(trimethylsilyl)methyl]mercury with an excess of zinc at ambient conditions. ... 

Ekong, D. E. U., J. I. Okogun, and B. L. Sondengam The Meliacins (Limonoids) Minor Constituents of Khaya anthotheca. Reduction of the Meliacins with Zinc-Copper Couple. J. Chem. Soc. Perkin Trans. I, 1975, 2118. 

The natural product (—)-hyoscyamine 12 was readily prepared in four simple steps from diastereoisomers 7 and 8 (Scheme 19.6). Treatment of 7 and 8 with zinc-copper couple followed by ketone reduction with excess DIBAL gave 6,7-dehydrotropine 11 stereoselectively in 92% yield for the two steps. The acylation of 11 with 0-acetyltropyl chloride and deprotection with hydrochloric acid gave 12 in 88% yield for the two steps. The intermediate 11 has proven to be a versatile intermediate, allowing access to a variety of important tropane alkaloids. 

With special techniques for the activation of the metal—e.g. for removal of the oxide layer, and the preparation of finely dispersed metal—the scope of the Refor-matsky reaction has been broadened, and yields have been markedly improved." The attempted activation of zinc by treatment with iodine or dibromomethane, or washing with dilute hydrochloric acid prior to use, often is only moderately successful. Much more effective is the use of special alloys—e.g. zinc-copper couple, or the reduction of zinc halides using potassium (the so-called Rieke procedure ) or potassium graphite. The application of ultrasound has also been reported. ... 

Zinc/copper couple (Zn/Cu), produced by the treatment of zinc with HC1, followed by the addition of copper(n) sulfate, has been known since the seminal work of Simmons and Smith.67 A less reactive form of activated zinc, but one that is sufficiently active for most applications, is produced by the treatment of the metal with 1,2-dibro-moethane, followed by Me3SiCl.68 The most reactive form of activated zinc, the so-called Rieke zinc (Zn ), is finely divided metallic zinc produced by the homogenous reduction of zinc halides in THF.69... 

Buynak et al. reported the synthesis of representative 7-vinylidenecephalosporine derivatives bearing an axial allene chirality (Scheme 4.5) [9]. A chiral allene 24 was prepared stereoselectively utilizing the reaction of an organocopper reagent with propargyl triflate 23, obtained by a diastereoselective ethynylation of the ketone 22 with ethynylmagnesium bromide. Terminally unsubstituted allene 26 was synthesized via bromination of the triflate 23 followed by reduction of the bromide 25 with a zinc-copper couple. 

The use of the zinc-copper couple to effect the reduction of the methanesulfonate 168 with rearrangement furnished 169 (Scheme 20.34) [10]. Treatment of 168 with methylmagnesium bromide in the presence of copper(I) cyanide to induce an SN2 -type reaction produced the methylated adduct 170. The half-life of the Myers-Saito cyclization of 169 is 66 h at 37 °C, whereas that of 170 is 100 min. The faster rate of cyclization for 170 has been attributed to a steric effect favoring the requisite s-cis or twisted s-cis conformation. 

Let us continue with the example of copper ions in contact with copper metal and zinc ions in contact with zinc metal. This combination is usually referred to as the Darnell cell or zinc/copper couple(Fig. 6.5a). For this electrochemical cell the reduction and oxidation processes responsible for the overall reaction are separated in space one half reaction taking place in one electrode compartment and the other takes place in the other compartment. 

Divalent chromium salts show very strong reducing properties. They are prepared by reduction of chromium(III) compounds with zinc [187] or a zinc-copper couple and form dark blue solutions extremely sensitive to air. Most frequently used salts are chromous chloride [7SS], chromous sulfate [189], and less often chromous acetate. Reductions of organic compounds are carried out in homogeneous solutions in aqueous methanol [190], acetone [191], acetic acid [192], dimethylformamide [193] or tetrahydrofuran [194] (Procedure 37, p. 214). 

Solutions of low-valence titanium chloride (titanium dichloride) are prepared in situ by reduction of solutions of titanium trichloride in tetrahydrofuran or 1,2-dimethoxyethane with lithium aluminum hydride [204, 205], with lithium or potassium [206], with magnesium [207, 208] or with a zinc-copper couple [209,210]. Such solutions effect hydrogenolysis of halogens [208], deoxygenation of epoxides [204] and reduction of aldehydes and ketones to alkenes [205,... 

An interesting reaction takes place when diketones with the keto groups in positions 1,4 or more remote are refluxed in dimethoxyethane with titanium dichloride prepared by reduction of titanium trichloride with a zinc-copper couple. By deoxygenation and intramolecular coupling, cycloalkenes with up to 22 members in the ring are obtained in yields of 50-95%. For example, 1-methyl-2-phenylcyclopentene was prepared in 70% yield from 1-phenyl-1,5-hexanedione, and 1,2-dimethylcyclohexadecene in 90% yield from 2,17-octa-decanedione [206, 210]. 

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