Synlett 2006(9): 1451-1452  
DOI: 10.1055/s-2006-944188
© Georg Thieme Verlag Stuttgart · New York

Synthetic Applications of Lithium Hydroxide

Fernando de Carvalho da Silva*
Instituto de Química, Universidade Federal Fluminense, UFF, CEP: 24020-150 Niterói, Rio de Janeiro, Brazil
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Further Information

Publication History

Publication Date:
22 May 2006 (online)


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]


(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


  • 1 Mischne M. Tetrahedron Lett.  2003,  44:  5823 
  • 2 Khim S. Dai M. Zhang X. Chen L. Pettus L. Thakkar K. Schultz AG. J. Org. Chem.  2004,  69:  7728 
  • 3 Lou Y. He Y. Kendall JT. Lemal DM. J. Org. Chem.  2003,  68:  3891 
  • 4 Yamada F. Hayashi T. Yamada K. Somei M. Heterocycles  2000,  53:  1881 
  • 5 Tsai W. Lin Y. Uang B. Tetrahedron: Asymmetry  1994,  5:  1195 
  • 6 Branderhorst HM. Kemmink J. Liskamp RMJ. Pieters RJ. Tetrahedron Lett.  2002,  43:  9601 
  • 7 Doyle MP. Dorow RL. Terpstra JW. Rodenhouse RA. J. Org. Chem.  1985,  50:  1663 
  • 8 Maryanoff BE. Reitz AB. Chem. Rev.  1989,  89:  901 
  • 9 Karagiozov SK. Abbott FS. Synth. Commun.  2004,  34:  871 
  • 10 Lattanzi A. Orelli LR. Barone P. Massa A. Iannece P. Scettri A. Tetrahedron Lett.  2003,  44:  1333