Synthetic Applications of Lithium Hydroxide

Introduction

Lithium hydroxide is a mild and efficient reagent used in several transformations in organic synthesis. It is used in tandem intramolecular aldol-aldol and sequential intramolecular Michael-aldol [1] reactions, as promoter of fragmentation reactions of optically active carbolactones providing γ-hydroxycyclohexenones and γ-butenolides, [2] in the synthesis of tropolones useful as bidentate ligands, [3] as promoter of glucosilation of 1-hydroxyindoles, [4] in the stereoselective Michael addition of thiols to N-meth­acryloylcamphorsultam followed by hydrolysis of the ­sulfonamides, [5] and it is applied in the deacylation of ­diazo-oxazolidones. [6] [7] In addition, lithium hydroxide has been widely employed in Horner-Wadsworth-Emmons (HWE) reactions for preparation of α,β-unsaturated esters, α-unsaturated esters [8] [9] and α,β-unsaturated nitriles. [10]

Abstracts

(A) Mischne reported a synthesis of [4.4.0] or [5.3.0] bicyclic frameworks achieved via sequential intramolecular Michael-aldol and tandem intramolecular aldol-aldol strategies, starting from acyclic precursors derived from β-ionone.1 (B) Khim et al. reported that lithium hydroxide induced fragmentation in butenolides and γ-hydroxycyclohexenones. The addition of LiOH (2.0 equiv) to a solution of the carbolactone in THF-H2O (5:1) at room temperature resulted in a mixture of the butenolides and γ-hydroxycyclohexenones in excellent yield.2 (C) Lemal and co-workers showed that anhydrous lithium hydroxide in benzene transforms tropone into pentafluorotropolone, which functions as a bidentate ligand (72% yield).3 (D) Yamada et al. reported a lithium hydroxide promoted gluco­sidation of 1-hydroxyindoles with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide followed by acetylation with Ac2O and pyridine.4 (E) Tsai et al. showed that lithium base (LiOH) promotes stereo­selective Michael addition of thiols to N-methacryloylcamphor­sultam and produced the corresponding addition products with a diastereomeric ratio of 66-90%. Hydrolysis of the Michael product with three equivalents of lithium hydroxide in THF-H2O gave the corresponding optically active β-thioester without racemization, and camphorsultam was recovered quantitatively.5 (F) Lithium hydroxide promotes selective deacylation of diazo-­oxazolidones resulting in N-diazoacetyl derivatives.6 7 (G) Lattanzi et al. showed a mild and practical procedure of LiOH-promoted HWE olefination, in which aldehydes were reacted with α-cyano phosphonates, yielding α,β-unsaturated nitriles. The ­reaction conditions are tolerated by functionalized ketones and the exclusive formation of (E)-γ-hydroxy α,β-unsaturated nitriles was observed.10 (H) Karagiozov and Abbott reported a stereoselective synthesis of α,β-unsaturated esters achieved via HWE reaction of β,β-disub­stituted α,β-unsaturated aldehydes. Thus, aldehydes undergo ole­fination with phosphonate carbanion generated from triethyl phosphonoacetate and lithium hydroxide to give (E)-α,β-unsaturated esters in excellent selectivity.9

References

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