Reduction using metal hydrides, solvent

Hydrogenolysis of epoxides to yield alcohols has been much reported in the patent literature, because of its importance as an industrial process, but studies on reactivity and selectivity have not been done systematically. The selectivity is highly dependent on the substituents, as in the case of reduction using metal hydrides. As a metal catalyst, Raney Ni was intensively examined in the early stage. It usually requires high pressures (ca. 100 atm) and temperatures (100 C), as shown in Table 10. Alcohols, benzene, THF and even water have been used as solvents. Accordingly, a hydroxy group in the epoxides remains intact, and hydrocarbons are formed only as by-products. In some cases by-product formation can... 

Remarkable solvent effects on the selective bond cleavage are observed in the reductive elimination of cis-stilbene episulfone by complex metal hydrides. When diethyl ether or [bis(2-methoxyethyl)]ether is used as the solvent, dibenzyl sulfone is formed along with cis-stilbene. However, no dibenzyl sulfone is produced when cis-stilbene episulfone is treated with lithium aluminum hydride in tetrahydrofuran at room temperature (equation 42). Elimination of phenylsulfonyl group by tri-n-butyltin hydride proceeds by a radical chain mechanism (equations 43 and 44). 

Tetraazamacrocyclic complexes131 of cobalt and nickel were found110 to be effective in facilitating the reduction of C02 at -1.3 to -1.6 V versus SCE (Table 8). An acetonitrile-water mixture and water were used as solvents, while in dry dimethylsulfoxide no catalytic reduction of C02 took place. Using an Hg electrode, both CO and H2 were produced, where total current efficiencies were greater than 90%. The turnover numbers of the catalysts were 2-9 h 1. The catalytic activity lasted for more than 24 h and the turnover numbers of the catalysts exceeded 100. A protic source was required to produce both CO and H2, and the authors suggested that both products may arise from a common intermediate, which is most likely a metal hydride. The applied potential for C02 reduction was further reduced by using illuminated p- Si in the presence of the above catalysts.111... 

Eq. (8) requires determination of the two-electron oxidation potential of L M by electrochemical methods. When combined with the two-electron reduction of protons in Eq. (9), the sum provides Eq. (10), the AGh- values of which can be compared for a series of metal hydrides. Another way to determine the AGh-entails the thermochemical cycle is shown in Scheme 7.3. This method requires measurement of the K of Eq. (11) for a metal complex capable of heterolytic cleavage of H2, using a base (B), where the pK., of BH+ must be known in the solvent in which the other measurements are conducted. In several cases, Du-Bois et al. were able to demonstrate that the two methods gave the same results. The thermodynamic hydricity data (AGh- in CH3CN) for a series of metal hydrides are listed in Table 7.4. Transition metal hydrides exhibit a remarkably large range of thermodynamic hydricity, spanning some 30 kcal mol-1. 

Although the method has been supplanted for synthetic purposes by the use of hydride donors, the reduction of ketones to alcohols by alkali metals in ammonia or alcohols provides some mechanistic insight into dissolving-metal reductions. The outcome of the reaction of ketones with metal reductants is determined by the fate of the initial ketyl intermediate formed by a single-electron transfer. The intermediate, depending on its structure and the reaction medium, may be protonated, disproportionate, or dimerize.137 In hydroxylic solvents such as liquid ammonia or in the presence of an alcohol, the protonation process dominates over dimerization. As will be discussed in Section 5.5.3, dimerization may become the dominant process under other conditions. 

Use of more efficient solvents (tetrahydrofuran, isopropyl ether, dimethoxyethane) or more soluble metal hydride reagents (sodium borohydride, lithium tributoxy aluminum hydride, sodium bis(2-methoxyethyl) aluminum hydride) favors the alternative reduction pathway to the hydroquinone. 

The reduction of tosylhydrazones by complex metal hydrides has been used very effectively to prepare saturated steroid hydrocarbons in high yields.317 In certain cases this reduction (with lithium aluminum hydride) takes a different course, and olefins are formed.318 The effect is dependent on both the reagent concentration and the steric environment of the hydrazone.319 Dilute reagent and hindered hydrazone favor olefins borohydride gives the saturated hydrocarbon. The hydrogen picked up in olefin formation comes from solvent, and in full reduction one comes from hydride and the other from solvent. This was shown by deuteriation experiments with the hydrazone (150) 319... 

Catalytic reduction of alkynes to ds-alkenes. This reduction is not possible with 10% Pd/C alone because this metal is too reactive and the alkane is formed readily. The selective reaction is possible if the Pd/C is deactivated by either Hg(0) or Pb(0), obtained by reduction of metal acetate with NaBH4. Sodium phosphinate, H2P02Na, is the preferred hydride donor. Since this donor is not soluble in the Organic solvents used, a phase-transfer catalyst, benzyltriethylammonium chloride, is added.3... 

Isopropylidene acetals (also known as acetonides) are used more frequently than any other protecting group for the protection of 1,2- and 1,3-diols. They are easily prepared and they are stable to most reaction conditions except pro-tic and Lewis acids. They typically survive strong metal hydride reactions, but the Lewis acidic nature of diisobutylalane and borane can cause complications as shown by the solvent-dependent reductive cleavage of a dioxolane in Scheme 3.L2... 

Lithium hydride is perhaps the most useful of the other metal hydrides. The principal limitation is poor solubiHty, which essentially limits reaction media to such solvents as dioxane and dibutyl ether. Sodium hydride, which is too insoluble to function efficiently in solvents, is an effective reducing agent for the production of silane when dissolved in a LiCl—KCl eutectic at 348 0 (63—65). Magnesium hydride has also been shown to be effective in the reduction of chloro- and fluorosilanes in solvent systems (66) and eutectic melts (67). 

This is a common method for preparing transition-metal hydrides (see Table I) " . Borohydride reduction is complex, e.g., RujfCOjj with NaBH in THF gives over a dozen products, but a few useful mechanistic generalizations can be offered. Syntheses of metal hydrides proceed through intermediate borohydride complexes. Electron-pair bases (an ethereal solvent may be sufficient) are then necessary to complex and remove BHj. In a few examples the borohydride complexes are observable ... 

Sodium borohydride, a representative borohydride reagent, behaves as an effective source of nucleophilic hydride in an aprotic polar solvent, such as DMSO, sulfolane, HMPA, DMF or diglyme, and is used for the reduction of alkyl halides. As shown in Table 3, primary and secondary iodides, bromides and chlorides are converted to hydrocarbons at temperatures between 25 and 100 C using sodium borohydride. Vicinal dihalides, such as 1,2-dibromooctane, are smoothly converted to the corresponding saturated hydrocarbons, in contrast to the reductions using LiAlH4 or low-valent metal salts, which predominantly afford alkenes. 

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