Lithium borohydride handling

Caution. Care should be used in handling lithium borohydride as it is toxic, and corrosive and ignites in the presence of water. Lithium borohydride should be stored under nitrogen or argon to maintain its purity and reactivity. 

Lithium borohydride is intermediate in activity as a reducing agent between lithium aluminium hydride and sodium borohydride. In addition to the reduction of aldehydes and ketones it will readily reduce esters to alcohols. It can be prepared in situ by the addition of an equivalent quantity of lithium chloride to a 1m solution of sodium borohydride in diglyme. Lithium borohydride should be handled with as much caution as lithium aluminum hydride. It may react rapidly and violently with water contact with skin and clothing should be avoided. 

Note. (1) Reaction of lithium borohydride with water may be rapid and violent do not expose to high humidity and avoid contact with eyes, skin and clothing (contact with cellulosic material may cause combustion). It should be handled with the same caution as is afforded to lithium aluminium hydride (Section 4.2.49, p. 445). 

L1AIH4 is often the best reagent, and gives alcohols by the mechanism we discussed in Chapter 12. As a milder alternative (L1AIH4 has caused countless fires through careless handling), lithium borohydride in alcoholic solution will reduce esters—in fact, it has useful selectivity for esters over acids or amides that LiAlH4 does not have. Sodium borohydride reduces most esters only rather slowly. 

The use of TEMPO to effect oxidative demercuration was originally demonstrated by Whitesides [16], and is attractive because it gives a functional handle for further structural elaboration. This technique was invoked by Kang in the syntheses of (-t-)-lactacystin and (-l-)-furanomycin [17]. For example, alkene 10 was subjected to mercurioamidation conditions to afford the cyclized organomercury intermediate 11 (Scheme 4). Treatment with lithium borohydride in the presence of TEMPO forms the unstable organomercury hydride. This fragments to release the primary carbon radical, which is trapped by TEMPO to yield the masked alcohol product 12, an intermediate in the synthesis of the neurotropic factor (-l-)-lactacystin. 

Lithinm borohydride, LiBH4, has attracted attention because of its high hydrogen content (18.5 wt%) compared with other metal borohydrides [39,40]. It is a hygroscopic white crystalline solid that is decomposed by water. Thus, it is generally handled under inert atmosphere. Lithium borohydride occurs as two phases under ambient pressure. The higher temperature phase forms above 107°C [41]. Lithium borohydride is currently manufactured in far smaller volumes than sodium borohydride. 

We don t need to spend much time on this—sodium borohydride does it very well, and is a lot easier to handle than lithium aluminium hydride. It is also more selective it will reduce this nitroketone, for example, where LiAlH4 would reduce the nitro group as well. 

Ozonides are rarely isolated [75, 76, 77, 78, 79], These substances tend to decompose, sometimes violently, on heating and must, therefore, be handled with utmost safety precautions (safety goggles or face shield, protective shield, and work in the hood). In most instances, ozonides are worked up in the same solutions in which they have been prepared. Depending on the desired final products, ozonide cleavage is done by reductive or oxidative methods. Reductions of ozonides to aldehydes are performed by catalytic hydrogenation over palladium on carbon or other supports [80, 81, 82, S3], platinum oxide [84], or Raney nickel [S5] and often by reduction with zinc in acetic acid [72, 81, 86, 87], Other reducing agents are tri-phenylphosphine [SS], trimethyl phosphite [89], dimethyl sulfide (DMS) [90, 91, 92], and sodium iodide [93], Lithium aluminum hydride [94, 95] and sodium borohydride [95, 96] convert ozonides into alcohols. 

Sodium borohydride is more convenient to handle than lithium aluminum hydride because it is not sensitive to water. In fact, sodium borohydride reduction can be carried out in aqueous solution, whereas lithium aluminum hydride requires strictly anhydrous conditions. Saturated aqueous solutions of sodium borohydride at 30°-40°C are stable in the presence of 0.2% sodium hydroxide. 

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