Lithium aluminum hydride as reducing agent

Lithium aluminum hydride as reducing agent permits formation of alcohol 40 in the first step. This is then convened to iodide 41. Another reduction with a nucleophilic boron reagent produces an ethyl group at C-13 and thus structure 12. 

With lithium aluminum hydride as reducing agent in tetrahydrofuran, bis[4-inethoxyphenyl] dilellurium was obtained in 93% yield1. 

Dialkyl alanes, R2AIH, are now widely used in place of lithium aluminum hydride as reducing agents because they are particularly readily... 

Various cyclopropanecarbonitriles have been converted to the corresponding cyclopro-panecarbaldehydes using diisopropylaluminum hydride, " - tri-hexylsilane, " lithium aluminum hydride, lithium diethoxyaluminum hydride, and lithium bis(2-methoxyethoxy)aluminum hydride as reducing agents. The yields were at best moderate. 

In ketones having a chiral cluster next to the carbonyl carbon reduction with lithium aluminum hydride gave one of the two possible diastereomers, erythro or threo, in larger proportions. The outcome of the reduction is determined by the approach of the reducing agent from the least hindered side (steric control of asymmetric induction) [828]. With lithium aluminum hydride as much as 80% of one diasteromer was obtained. This ratio is higher with more bulky reducing hydrides [837]. 

Isocyanides have been reduced to N-methylamines with lithium aluminum hydride as well as with other reducing agents. 

Lithium aluminum hydride usually reduces carbonyl groups without affecting carbon-carbon double bonds. It is, in addition, a good reducing agent for carbonyl groups of carboxylic acids, esters, and other acid derivatives, as will be described in Chapter 18. 

Disni.wion Lithium aluminum hydride as a reducing agent is too basic for use... 

The ability of reducing agents, such as lithium aluminum hydride, to reduce halides and sulfonates to their corresponding alkyl derivatives is well known. Lithium aluminum hydride is also selective for the reduction of primary halides and sulfonates over secondary analogs. As shown in Scheme 6.70, this reaction was applied to a bis-tosylate with the major isolated product being the mono-tosylate with deoxygenation at C-6 [109]. 

The hydride is similar to lithium aluminum hydride as a reducing agent. In tetrahydrofurane or tetrahydrofurane-pyridine at —65 to —45° it reduces esters of carboxylic acids to aldehydes in yields of 50-85%. Aliphatic aldehydes are obtained in higher yields than aromatic aldehydes. Under the same conditions lithium aluminum hydride gives lower yields. ... 

DIRECT REDUCING AGENT IN CERTAIN ORGANIC REACTIONS. The USe of lithium aluminum hydride as a selective reducing agent has enjoyed tremendous popularity in the laboratory, since its discovery was reported by Schlesinger and coworkers in 1947 (11). The use of lithium aluminum hydride reductions has become so well known that little in the way of elaboration is needed here. 

Carboxylic acids are exceedingly difficult to reduce Acetic acid for example is often used as a solvent in catalytic hydrogenations because it is inert under the reaction con ditions A very powerful reducing agent is required to convert a carboxylic acid to a pri mary alcohol Lithium aluminum hydride is that reducing agent... 

Lithium borohydride is a more powerful reducing agent than sodium borohydride, but not as powerful as lithium aluminum hydride (Table 6). In contrast to sodium borohydride, the lithium salt, ia general, reduces esters to the corresponding primary alcohol ia refluxing ethers. An equimolar mixture of sodium or potassium borohydride and a lithium haUde can also be used for this purpose (21,22). 

Iodine azide, on the other hand, forms pure adducts with A -, A - and A -steroids by a mechanism analogous to that proposed for iodine isocyanate additions. Reduction of such adducts can lead to aziridines. However, most reducing agents effect elimination of the elements of iodine azide from the /mwj -diaxial adducts of the A - and A -olefins rather than reduction of the azide function to the iodo amine. Thus, this sequence appears to be of little value for the synthesis of A-, B- or C-ring aziridines. It is worthy to note that based on experience with nonsteroidal systems the application of electrophilic reducing agents such as diborane or lithium aluminum hydride-aluminum chloride may yet prove effective for the desired reduction. Lithium aluminum hydride accomplishes aziridine formation from the A -adducts, Le., 16 -azido-17a-iodoandrostanes (97) in a one-step reaction. The scope of this addition has been considerably enhanced by the recent... 

Acylation of norephedrine (56) with the acid chloride from benzoylglycolic acid leads to the amide (57), Reduction with lithium aluminum hydride serves both to reduce the amide to the amine and to remove the protecting group by reduction (58), Cyclization by means of sulfuric acid (probably via the benzylic carbonium ion) affords phenmetrazine (59), In a related process, alkylation of ephedrine itself (60) with ethylene oxide gives the diol, 61, (The secondary nature of the amine in 60 eliminates the complication of dialkylation and thus the need to go through the amide.) Cyclization as above affords phendimetra-zine (62), - Both these agents show activity related to the parent acyclic molecule that is, the agents are CNS stimulants... 

As in the preceding experiment, a lithium aluminum hydride-aluminum chloride reducing agent is prepared by the addition of 1.67 g (0.044 mole) of lithium aluminum hydride in 50 ml of anhydrous ether to 24.2 g (0.18 mole) of anhydrous aluminum chloride in 50-55 ml of anhydrous ether. 

Azo, azoxy, and hydrazo compounds can all be reduced to amines. Metals (notably zinc) and acids, and Na2S204, are frequently used as reducing agents. Borane reduces azo compounds to amines, though it does not reduce nitro compounds. " Lithium aluminum hydride does not reduee hydrazo compounds or azo compounds, though with the latter, hydrazo compounds are sometimes isolated. With azoxy compounds, LiAHLj gives only azo compounds (19-48). 

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