Reductions with Metal Hydrides

The metal hydrides exhibit different reducing properties. The complex metal hydrides (LiAlH4, NaBH4) are nucleophilic in character hydride is transported from the complex anion to the electron-deficient centers of the functional groups. Another group of metal hydrides (boranes, alanes) are strong Lewis acids they interact with centers that are relatively richer in electrons. The selectivity of the reduction can be improved and the scope of its application can be extended by the joint use of these two types (mixed hydrides). 

In the group of electrophilic reagents the reducing power of B2H6 is increased by the addition of a catalytic amount of NaBH4 or BF3 the reaction is accelerated, but at the same time the reaction pathway is changed. New alkylboranes have been developed, for example, thexylborane 119 and 9-borabicyclo[3.3.1]nonane (9-BBN) 120.  

The reactivity of AIH3 has been varied by the preparation of alkyl- and alkoxyalanes.  

The mechanism and stereochemistry of the reduction with metal hydride has been dealt with in many articles. It may be stated in general that the structure of the oxirane and the nature of the reducing agent exert great effects on the rate and pathway of the reaction. 

Reduction with LiAlH4 is an Sjv2-type reaction the complex anion attacks as a hydride-carrier on the side opposite to the oxirane ring if there is no steric hindrance, the ring is opened regiospecifically at the least-substituted carbon atom and yields the more-substituted alcohols. The reactivity increases in the sequence UBH4, UAIH4, and Li(sec-Bu)2BH. Examinations on optically active 1-aryl-l,2-epoxypropane and 2-aryl-2,3-epoxybutane, and 1-phenyl- and 

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The salt 55 (R = H) did not cyclize on reduction with metal hydrides, but instead yielded the tryptamine derivative 58 (R = H) as the sole... 

Eliel, E. L., and M. N. Rerick Reduction with Metal Hydrides, VIII. Reduction of Ketones and Epimerization of Alcohols with Lithium-Aluminium Hydride — Aluminium Chloride. J. Amer. chem. Soc. 82, 1367 (1960). 

Reductions in organic chemistry utilizing zinc, iron, and hydrogen sulfide, have been performed since the 1840 s. Catalytic hydrogenation came about in 1897, and reduction with metal hydrides came into usage in 1947. 

Similarly reductions with metal hydrides, metals and other compounds may give predominantly one isomer. The stereochemical outcome depends strongly on the structure of the ketone and on the reagent, and may be alfected by the solvents. 

Fig. (2). The cyclization of enone (9), gives origin of two Cyclized products (10) and (11). Ketone (10), Ketone (10) is converted to the saturated ketone (14)under standard organic reactions.Bromination and dehydrobromination of ketone (14) yields the a,P-unsaturated ketone (IS), which on subjection to catalytic hydrogenation affords (16) and this on reduction, produces alcohol (17). The compound (13) yields (18) by standard reactions that are used for the transformation of (12) to (16). Reduction with metal hydride followed by oxidation affords ketone (11), which is converted to alcohol (17)...

The state of the art of reductions with metal hydrides a decade ago was the subject of comprehensive reviews. A detailed survey of reductions of carbonyl compounds with alkali and alkaline earth metal hydrides, borane and derivatives, alane and derivatives, metal borohydrides, metal aluminohydrides, silanes, stannanes and transition metal hydrides was compiled. The properties, preparation and applications of each reagent were discussed together with methods for their determination, handling techniques... 

Dissolving metal reductions remain the method of choice, and are frequently the only viable method, for the reduction of sterically hindered cyclohexanones to equatorial alcohols. In the early 1950s it was found that reduction of 11-keto steroids using either Na-propan-l-oP or Li-NHs-dioxane-ethanol gave good yields of the equatorial I la-alcohol. 11-Keto steroids, such as androstan-11-one (29 equation 12) have two axial methyl groups in a 1,3-relationship to the carbonyl group and afford exclusively the axial 11 P-ol (30) on reduction with metal hydrides. 

Benzotriazoles, like their monocyclic counterparts, are often synthesized by reductive cyclizations and it is only when they are activated as salts that reductions with metal hydrides occur. Potassium borohydride, for example, reacts with aqueous solutions of the salt (261) to give 2-methylaminoaniline (262). Some A-demethylation leading to the triazole (263) also takes place, and this may be caused by the prevailing alkaline reaction conditions. LAH in diethyl ether is a more effective reagent for the reductive ring opening of benzotriazoles, and this reagent also cleaves 1,3-dimethylbenzotriazolium methylsulfate (264) to l,2-di(methylamino)benzene(265)." ... 

Very extensive work relating to the field of reduction with metal hydrides has been continued by H. C. Brown and his colleagues. The results of their activities and those of other authors have been treated in a recent review earlier reviews exist as well. ... 

As discussed in Section 3.1.11.1, which covers the reductive cleavage of the 3-hydroxy sulfone derivatives to alkenes, the Julia reaction proceeds by the formation of an anion that is able to equilibrate to the thermodynamic mixture prior to elimination. Therefore, there is no inherent advantage in producing the erthyro- or threo-fi-hydroxy sulfone selectively fix>m the keto sulfone. The ( )/(Z)-mixture of alkenes should be the same. This method is used to produce alkenes in cases where the acid derivative is more readily available or more reactive. The reaction of the sulfone anion with esters to form the keto sulfone, followed by reduction with metal hydrides has been studied. The steric effects in the reduction do become important for the reaction to produce vinyl sulfones, which are formed from the anti elimination of the 3-hydroxy sulfone adduct, as mentioned in Section 3.1.11.6.2. Some examples of the use of esters are presented below. 

Often indolo[2,3-fl]quinolizines (e.g., 109) form the skeletal basis for work in the indole and oxindole alkaloid field. These are most often prepared from pyridinyl- (108) or quinolinylindolethanes via reduction with metal hydrides. The tetrahydropyridines then undergo acid-catalyzed ring closure, often giving mixtures of several compounds (109,110, 111). 

Ketenes react at the carbonyl group of 215a to eliminate carbon dioxide and produce the more extended conjugated system (as in 216 obtained from a cycloheptatrienylidene ketene.)316 Reduction with metal hydride removes the carbonyl oxygen and induces coupling of two residues at the 4-position.317 Addition of dienophiles is not observed in the parent system, but the furan part of the dibenzotropone (217) readily adds quinones and other such addenda.318... 

Reductions with metal hydrides are often preliminary steps for additional reactions. For instance, a product of UAIH4 reduction of syndiotactic poly(methyl methacrylate) can be reacted with succinic anhydride and then converted to an amide " ... 

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