Lithium aluminum hydride mechanism

Sodium borohydride and lithium aluminum hydride react with carbonyl compounds in much the same way that Grignard reagents do except that they function as hydride donors rather than as carbanion sources Figure 15 2 outlines the general mechanism for the sodium borohydride reduction of an aldehyde or ketone (R2C=0) Two points are especially important about this process... 

The mechanism of lithium aluminum hydride reduction of aldehydes and ketones IS analogous to that of sodium borohydride except that the reduction and hydrolysis... 

Treatment of thiiranes with lithium aluminum hydride gives a thiolate ion formed by attack of hydride ion on the least hindered carbon atoms (76RCR25), The mechanism is 5n2, inversion occurring at the site of attack. Polymerization initiated by the thiolate ion is a side reaction and may even be the predominant reaction, e.g. with 2-phenoxymethylthiirane. Use of THF instead of ether as solvent is said to favor polymerization. Tetrahydroborates do not reduce the thiirane ring under mild conditions and can be used to reduce other functional groups in the presence of the episulfide. Sodium in ammonia reduces norbornene episulfide to the exo thiol. 

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... 

After drying under vacuum this iodo azide (2.43 g) is suspended in 50 ml of ether and added with stirring to a cold (0°) slurry of lithium aluminum hydride (1.2 g) in 70 ml of anhydrous ether in a 250 ml 3-necked flask (fitted with a reflux condenser and a mechanical stirrer with a Teflon blade). The remaining traces of the iodo azide are rinsed into the reaction flask with three 10 ml portions of ether. The reaction mixture is allowed to warm to room temperature and to stir for a total period of 11 hr. 

The reduction of iminium salts can be achieved by a variety of methods. Some of the methods have been studied primarily on quaternary salts of aromatic bases, but the results can be extrapolated to simple iminium salts in most cases. The reagents available for reduction of iminium salts are sodium amalgam (52), sodium hydrosulfite (5i), potassium borohydride (54,55), sodium borohydride (56,57), lithium aluminum hydride (5 ), formic acid (59-63), H, and platinum oxide (47). The scope and mechanism of reduction of nitrogen heterocycles with complex metal hydrides has been recently reviewed (5,64), and will be presented here only briefly. 

A three-necked, round-bottom, 500-ml flask is fitted with a mechanical stirrer, a dropping funnel, and a condenser with openings protected by drying tubes. Lithium aluminum hydride (3.5 g) is placed in the flask with 100 ml of anhydrous ether, and... 

In a 500-ml three-necked flask, equipped with a mechanical stirrer, a dropping funnel, and a reflux condenser (drying tube), is placed 6.7 g (0.05 mole) of anhydrous aluminum chloride. The flask is cooled in an ice bath, 50 ml of dry ether is slowly added from the dropping funnel, and the mixture is stirred briefly. Powdered lithium aluminum hydride (0.6 g) is placed in a 100-ml flask fitted with a condenser, and 20 ml of dry ether is added slowly from the top of the condenser while the flask is cooled in an ice bath. The mixture is refluxed for 30 minutes then cooled, and the resulting slurry is transferred to the dropping funnel on the 500-ml flask. The slurry is added to the stirred ethereal solution of aluminum chloride over 10 minutes, and the reaction mixture is stirred for an additional 30 minutes without cooling to complete the formation of the mixed hydride . 

Epoxides are reduced by treatment with lithium aluminum hydride to yield alcohols. Propose a mechanism for this reaction. 

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). 

From the equation showing the mechanism it is evident that 1 mol of lithium aluminum hydride can reduce as many as four molecules of a carbonyl compound, aldehyde or ketone. The stoichiometric equivalent of lithium aluminum hydride is therefore one fourth of its molecule, i.e. 9.5 g/mol, as much as 2 g or 22.4 liters of hydrogen. Decomposition of 1 mol of lithium aluminum hydride with water generates four molecules of hydrogen, four hydrogens from the hydride and four from water. 

Alkyl bromides and especially alkyl iodides are reduced faster than chlorides. Catalytic hydrogenation was accomplished in good yields using Raney nickel in the presence of potassium hydroxide [63] Procedure 5, p. 205). More frequently, bromides and iodides are reduced by hydrides [505] and complex hydrides in good to excellent yields [501, 504]. Most powerful are lithium triethylborohydride and lithium aluminum hydride [506]. Sodium borohydride reacts much more slowly. Since the complex hydrides are believed to react by an S 2 mechanism [505, 511], it is not surprising that secondary bromides and iodides react more slowly than the primary ones [506]. The reagent prepared from trimethoxylithium aluminum deuteride and cuprous iodide... 

Strong reducing agents like sodium borohydride and lithium aluminum hydride are capable of reducing aldehydes to primary alcohols and ketones to secondary alcohols. The general reaction is the reverse of the reactions used to form aldehydes and ketones by the oxidation of primary and secondary alcohols, respectively (to review, see the earlier section Oxidation reactions ). However, the mechanisms for reduction are different. 

General Comments. The formation of deoxy sugars by hydrogenation over Raney nickel often leads to the abnormal isomer (namely, that formed by diequatorial opening of the oxirane ring) as the major product, in contrast to the product afforded by lithium aluminum hydride this suggests that a different mechanism is involved in the nickel-catalyzed reaction. 

S)-2-Chloropropan-l-ol. Into a 2-L, three-necked, round-bottomed flask equipped with a mechanical stirrer, 250 mL dropping funnel, stopper (Note l) and an efficient reflux condenser fitted with a calcium chloride drying tube, is placed 9.1 g (0.24 mol) of lithium aluminum hydride, 400 mL of dry diethyl ether is added with caution. The slurry is cooled in an ice bath and a... 

The complexation, proposed by R. K. Brown and coworkers (Refs. 199-207), of either one of the ring-oxygen atoms by aluminum chloride is reproduced here as a simplification. It seems evident that the intimate mechanism does not imply (i) attack by aluminum chloride, and then (ii) reduction by lithium aluminum hydride actually, the mixed hydride is the reactive species (Ref. 210), and its identity depends on the ratio between the Lewis acid and the hydride (see, for instance, Refs. 211 and 212, and references cited therein, for a discussion of the nature of mixed hydrides). 

The main methods of reducing ketones to alcohols are (a) use of complex metal hydrides (b) use of alkali metals in alcohols or liquid ammonia or amines 221 (c) catalytic hydrogenation 14,217 (d) Meerwein-Ponndorf reduction.169,249 The reduction of organic compounds by complex metal hydrides, first reported in 1947,174 is a widely used technique. This chapter reviews first the main metal hydride reagents, their reactivities towards various functional groups and the conditions under which they are used to reduce ketones. The reduction of ketones by hydrides is then discussed under the headings of mechanism and stereochemistry, reduction of unsaturated ketones, and stereochemistry and selectivity of reduction of steroidal ketones. Finally reductions with the mixed hydride reagent of lithium aluminum hydride and aluminum chloride, with diborane and with iridium complexes, are briefly described. 

---