Lithium benzyloxide

A solution of lithium benzyloxide is prepared by addition of 56 mL (90 mmol) of 1.6 M butyllithium in hexane to 9.2 mL (88 mmol) of benzenemethanol in 100 mL of THF at — 78 C, followed by the addition of rigorously anhyd DMSO. This solution is added to a solution of 16.38 g (71.7 mmol) of (S)-pinanediol (chloromethyl)boronatc in 60 mL of THF stirred at — 78 °C. The mixture is allowed to warm to r.t. and then heated at 45-50rC for 3 h, at which time TLC indicates the reaction is complete. The mixture is worked up by acidificalion with 0.5 M aq hydrochloric acid followed by diethyl ether extraction. The diethyl ether, DMSO, and benzenemethanol are distilled under vacuum and the residue is chromatographed on silica gel with 10% ethyl acetate in hexane. The product is distilled, and solidifies on cooling vield 19.8 g (92%) bp 158-162 °C (0.2 Torr) mp 25-27°C. 

In reactions with acyclic dienes, the stereoselection with the (S)-valinol-derived cro-tonate imides is only about 3 1, but diastereoselection is high with N-acyl oxazolidines derived from phenylalanine. The chiral auxiliary is cleaved by transesterification with lithium benzyloxide in 85-95% yield. ... 

Benzyl (25)-2-(l,2-Di-terf-butyIoxycarbonylhydrazino)aIkanecarboxylates 5 by Lithium Benzyloxide Transesterification of 2 General Procedure Method C16 ... 

In 1982, Evans reported that the alkylation of oxazolidinone imides appeared to be superior to either oxazolines or prolinol amides from a practical standpoint, since they are significantly easier to cleave [83]. As shown in Scheme 3.17, enolate formation is at least 99% stereoselective for the Z(0)-enolate, which is chelated to the oxazolidinone carbonyl oxygen as shown. From this intermediate, approach of the electrophile is favored from the Si face to give the monoalkylated acyl oxazolidinone as shown. Table 3.6 lists several examples of this process. As can be seen from the last entry in the table, alkylation with unactivated alkyl halides is less efficient, and this low nucleophilicity is the primary weakness of this method. Following alkylation, the chiral auxiliary may be removed by lithium hydroxide or hydroperoxide hydrolysis [84], lithium benzyloxide transesterification, or LAH reduction [85]. Evans has used this methology in several total syntheses. One of the earliest was the Prelog-Djerassi lactone [86] and one of the more recent is ionomycin [87] (Figure 3.8). 

Mukaiyama developed a variety of catalytic carbon-carbon bond-forming reactions with the use of trimethylsilyl nucleophiles in the presence of simple lithium Lewis-base catalysts, such as lithium acetate, lithium pyrro-lidone, lithium succinimide, lithium benzamide, lithium diphenylamide, and lithium benzyloxide (Scheme 2.1). For example, the Mukaiyama aldol... 

---