Reduction by hydrides

Bicyclo[3.3.1]nonan-9-one is another ketone that exhibits interesting stereoselectivity. Reduction by hydride donors is preferentially syn to electron-attracting substituents at C-5 (X = EWG in the structure shown below) and anti to electron-releasing substituents (X = ERG below). These effects are observed even for differentially substituted phenyl... 

Reduction by hydride transfer from the organometallic reagent can become predominant if bulky organometallics are employed. 

B. Reductions by Hydrides, Metals and Single-Electron-Transfer (SET)... 

D. C. Wigeield, Stereochemistry and Mechanism of Ketone Reductions by Hydride Reagents, Tetrahedron 35,449 (1979). 

Trinitrophenol is degraded in a reaction involving ring reduction by hydride transfer from an NADPH-dependent F420 reductase (Hofmann et al. 2004). 

The interpretation of the basis for this stereoselectivity can be made in terms of the steric, torsional, and stereoelectronic effects discussed in connection with reduction by hydrides. It has been found that crown ethers enhance stereoselectivity in the reaction of both Grignard reagents and alkyllithium compounds.119 This effect was attributed to decreased electrophilicity of the metal cations in the presence of the crown ether. The attenuated reactivity leads to greater selectivity. 

Similar reductions are achieved by trialkylboranes [S26]. These reactions, although different in nature from the reductions by hydrides and complex hydrides, were amongst the first applications of boranes and alanes for the reduction of organic compounds. 

The reactions of simple imine complexes are mainly restricted to hydrogenation or reduction by hydrides or by addition of nucleophiles such as alcohols. For example, complexes of macrocycles (18) undergo catalytic reduction to generate two chiral centres.66 Sodium borohydride has been used to reduce the imine complexes shown in equation (3).67 This technique enables convenient removal of the metal and the consequent synthesis of the reduced free macrocycles. Complexes of the aldimine (20) undergo nucleophilic addition of alcohols.49... 

The structure of this cyclic intermediate B, which contains an immonium structure, suggests the possibility of undergoing a facile reduction by hydride, if present during the course of photocyclization. This expectation was visualized as expected on the various enamides and therefore opened up a new phase of the application of enamide photocyclization (15) (Scheme 16). 

Reduction by hydrides of two types of organometallic compounds has received some synthetic applications so only these cases will be discussed. 

It is worth noting that even lithium aluminum hydride gives as the main isolatable substance the product of Sn2 reduction by hydride ion ... 

A variety of chiral auxiliaries have been used to direct the course of carbonyl reductions by hydride reducing agents. The great majority of them contain heteroatoms capable of coordinating to metal ions, and appear to owe their effectiveness either to their ability to participate in chelated intermediates or to the ability of Lhe heteroatom to bind to a reagent and control its direction of approach. 

The cathodic reduction of 2 leading to a more or less selective cleavage of the S—O bond, appears to be the main goal of different studies in this field because those esters are considered as forms protecting the alcohol ROH. Interest in cathodic deprotection lies mainly in the fact that alternative chemical processes (solvolysis or reduction by hydrides) lead to racemization or inversion of the R group. 

Lactams are cyclic amides and they are reduced by LiAlHq to the cyclic amine. The reduction of a typical lactam such as 2-pyrrolidinone derivative 36 presumably proceeds via initial formation of the a-amino alcohol (37), followed by elimination to an iminium salt (38), and then reduction by hydride to give the amine (39). This reaction is very useful in the synthesis of alkaloids, as seen in the reduction of 40 to 41 in 88% yield as part of Overman s synthesis of (-i-)-aloperine. O The lactam nitrogen is significantly less basic than the corresponding amine and cyclic amines are often protected as the lactam. The amine is then unmasked late in the synthetic sequence by hydride reduction. 

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