Reduction metal hydride

A direct attack of nucleophiles on the sulfur atom of the sulfone or sulfoxide group in acyclic or large-ring sulfones and sulfoxides is rather rare, or unknown, excluding metal hydride reductions and/or reductive deoxygenations. The situation is completely different in the three-membered ring systems. 

H. O. House, Metal Hydride Reductions and Related Reactions, Synthetic Reactions, S. 45, W. A. Benjamin Inc., Menlo Park 1972. 

With an efficient synthesis of allylic alcohol 46 in our hands, our attention turned to the selective reduction of the double bond. As stated above, we intended to use the hydroxy group in 46 to deliver hydride from the same face as the hydroxy group. Mainly there were two methods available (i) transition metal-mediated hydrogenation and (ii) metal hydride reduction. 

Asymmetric reduction of carbonyl compounds can usually be achieved either through direct catalytic hydrogenation or by metal hydride reduction. It should be mentioned here that reduction of carbonyl compounds by catalytic hydrogenation may not be chemoselective. Other co-existing functional groups such as the C=C bond may also undergo hydrogenation. 

Crown ethers have also been found to lower the rate of reduction by metal hydrides. Wiegers and Smith (1978) reported that the rate of reduction of camphor by LiAlH4 in tetrahydrofuran was depressed by a factor of 6 on addition of one equivalent of crown ether [201]. They also concluded that, although the free cation shows a catalytic effect in metal hydride reduction, it is not indispensable. Dibenzo-18-crown-6 [11] was also found to lower the rate of... 

Amides seem to behave differently, with complex metal hydride reduction giving an amine, effectively converting the carbonyl group to a methylene (see Section 7.11). 

Dissolving metal reductions were among the first reductions of organic compounds discovered some 130 years ago. Although overshadowed by more universal catalytic hydrogenation and metal hydride reductions, metals are still used for reductions of polar compounds and selective reductions of specific types of bonds and functions. Almost the same results are obtained by electrolytic reduction. 

Many synthetic methods have been reported for the pyrrolidine alkaloids, including procedures based on the Hofmann-Loffler reaction 132,412), the metal hydride reduction of pyrrolines 413,414), the a-alkylation of N-nitro-sopyrrolidine 412,415), the catalytic hydrogenation of pyrroles 133), the reductive amination of 1,4-diketones 25,138), the direct alkylation of 1-methoxy-carbonyl-3-pyrroline 416), the versatile synthesis from the Lukes-Sorm dilac-... 

A series of flavan-4-ols, e.g., 108, was conveniently prepared by metal hydride reduction of the corresponding flavanone. The flavan-4-ols were converted into the 4-methoxyflavans, e.g., 109, by acid-catalyzed solvolysis in methanol. Both these classes of compounds are currently evaluated as anticancer drugs. Enantiomerically enriched cA-flavan-4-ols have been prepared by lipase-catalyzed kinetic resolution of racemic counterparts. ... 

Amides, azides and nitriles are reduced to amines by catalytic hydrogenation (H2/Pd—C or H2/Pt—C) as well as metal hydride reduction (LiAlH4). They are less reactive towards the metal hydride reduction, and cannot be reduced by NaBITj. Unlike the LiAlIU reduction of all other carboxylic acid derivatives, which affords 1° alcohols, the LiAlIU reduction of amides, azides and nitriles yields amines. Acid is not used in the work-up step, since amines are basic. Thus, hydrolytic work-up is employed to afford amines. When the nitrile group is reduced, an NH2 and an extra CH2 are introduced into the molecule. 

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