Lithium Hydroperoxide

LiOOH

[23594-83-4] (.H2O)

[54637-08-0]  · HLiO2  · Lithium Hydroperoxide  · (MW 39.95)

(nonbasic hydrolysis of imides, amides, and esters; nondestructive recovery of chiral auxiliaries3)

Physical Data: hydrate: white crystalline solid; d 1.69 g cm-3.

Solubility: sol THF/H2O (3:1), dioxane.

Preparative Methods: prepared in situ from Lithium Hydroxide and aq. Hydrogen Peroxide.

Handling, Storage, and Precautions: reagent is typically generated in situ immediately prior to use. The hydrate can be prepared in an inert atmosphere from ethanolic LiOEt and 30% H2O2.1 Extended storage over desiccants such as P2O5 leads to the formation of Li2O2. LiOOH.H2O reacts spontaneously with atmospheric CO2 to form Li2CO3 and O2, and gradually decomposes on standing at room temperature to LiOH.H2O.

Cleavage of N-Acyloxazolidones and Related Imides.

Effective use of the high diastereoselectivity realized from enolate chemistry of optically active N-acyloxazolidones,2a-d or Diels-Alder cycloaddition2e reactions of their a,b-unsaturated derivatives, depends upon clean removal of the chiral auxiliary in a regioselective fashion and without racemization at any acidic chiral centers. Lithium hydroperoxide was originally introduced as an alternative to reductive cleavage of sensitive b,g-unsaturated N-acyloxazolidones with Lithium Borohydride, and showed exceptional regioselectivity for attack at the exocyclic carbonyl with no epimerization or double bond conjugation (eq 1).3

In a subsequent, more complete study, lithium hydroperoxide was demonstrated to be the reagent of choice for regioselective cleavage of a variety of sterically hindered N-acyloxazolidones which underwent competing oxazolidone ring opening with LiOH or LiOCH2Ph (eq 2).4 Similarly high selectivity for attack at the more hindered carbonyl group was also seen with an acyclic imide (eq 3). The reaction is usually carried out in aqueous THF and is typically quenched with aqueous Na2SO3 to reduce the peracid intermediate and consume unreacted LiOOH. Recent examples include the use of this cleavage step in the synthesis of amino acid derivatives,5a the calyculins,5b-c macbecin,5d baclofen,5e and polyketide intermediates in the biosynthesis of nargenicin.5f

In a route to optically active a-alkylsuccinates, LiOOH proved to be highly chemoselective for imide cleavage, with no competing cleavage of a methyl ester also present.6 In a recent approach to b-amino acids, regioselective cleavage of an intermediate in the synthesis of thienomycin was found to require the addition of DMF (3:3:1 DMF/THF/H2O) as a cosolvent (eq 4).7 Importantly, this reagent can be used in the presence of a-phenylselenyl groups with no competing oxidation of the selenide.8

Other examples (shown in 1-6) include the cleavage of N-acylbenzoxazolinones,9 carbohydrate-derived N-acyloxazolidones,10 camphor-derived N-acyloxazolidonethiones,11 camphor-derived imides,12 N-acylpiperidone derivatives of Kemp's triacid,13 and chiral N-acylpyrimidones.14 Also, cleavage of N-acyl and N-carbamoyl derivatives of an oxazolidone obtained from endo-borneol has been described as a method for resolving racemic carboxylic acids or alcohols.15

Cleavage of N-Acylsultams.

In addition to imide carbonyls, optically active N-acylsultams can be cleaved using LiOOH. Following either asymmetric alkylation16a or conjugate addition,16b bornanesultam chiral auxiliaries can be removed with good recovery and without racemization of the resulting carboxylic acids (eq 5). This cleavage method was also used in the preparation of a toluenesultam chiral auxiliary.16c

Cleavage of Esters and Amides.

Notwithstanding the previously noted chemoselectivity for imides,6 LiOOH has been used to saponify esters under mild conditions. For example, in a synthesis of a bifunctional chelate molecule, an ethyl ester was cleaved in high yield using LiOOH.17 Also, in the synthesis of a heparin analog, simultaneous deprotection of a series of primary and secondary acetates and two methyl esters was effected via LiOOH without the intervention of undesired b-elimination.18 LiOOH was also used to cleave a methyl ester in a recent total synthesis of the leukotriene precursor (15S)-HPETE (eq 6).19 Interestingly, cycloheptene was used to reduce the resulting peroxy acid selectively in the presence of an allylic hydroperoxide. Finally, deprotection of an N-formylamino polyol was carried out using LiOOH/THF.20 The authors noted that stabilization of the THF with BHT was desirable to suppress side reactions involving radicals.


1. Cohen, A. J. Inorg. Synth. 1957, 5, 2.
2. (a) Evans, D. A.; Ennis, M. D.; Mathre, D. J. JACS 1982, 104, 1737. (b) Evans, D. A.; Ennis, M. D.; Le, T. L.; Mandel, N.; Mandel, G. JACS 1984, 106, 1154. (c) Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F. JACS 1986, 108, 6395. (d) Evans, D. A.; Sjogren, E. B.; Weber, A. E.; Conn, R. E. TL 1987, 28, 39. (e) Evans, D. A.; Chapman, K. T.; Bisaha, J. JACS 1984, 106, 4261.
3. Evans, D. A.; Sjogren, E. B.; Bartroli, J.; Dow, R. L. TL 1986, 27, 4957.
4. Evans, D. A.; Britton, T. C.; Ellman, J. A. TL 1987, 28, 6141.
5. (a) Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F., Jr. T 1988, 44, 5525. (b) Smith, A. B., III; Salvatore, B. A.; Hull, K. G.; Duan, J. J.-W. TL 1991, 32, 4859. (c) Evans, D. A.; Gage, J. R.; Leighton, J. L.; Kim, A. S. JOC 1992, 57, 1961. (d) Evans, D. A.; Miller, S. J.; Ennis, M. D. JOC 1993, 58, 471. (e) Schoenfelder, A.; Mann, A.; Le Coz, S. SL 1993, 63. (f) Cane, D. E.; Tan, W.; Ott, W. R. JACS 1993, 115, 527.
6. Fadel, A.; Salaün, J. TL 1988, 29, 6257.
7. Jacobi, P. A.; Zheng, W. TL 1993, 34, 2585.
8. Holmes, A. B.; Nadin, A.; O'Hanlon, P. J.; Pearson, N. D. TA 1992, 3, 1289.
9. Corey, E. J.; Houpis, I. N. TL 1993, 34, 2421.
10. Rück, K.; Kunz, H. SL 1992, 343.
11. Yan, T.-H.; Tan, C.-W.; Lee, H.-C.; Lo, H.-C.; Huang, T.-Y. JACS 1993, 115, 2613.
12. Boeckman, R. K., Jr.; Nelson, S. G.; Gaul, M. D. JACS 1992, 114, 2258.
13. Jeong, K.-S.; Parris, K.; Ballester, P.; Rebek, J., Jr. AG(E) 1990, 29, 555.
14. (a) Negrete, G. R.; Konopelski, J. P. TA 1991, 2, 105. (b) Chu, K. S.; Negrete, G. R.; Konopelski, J. P.; Lakner, F. J.; Woo, N.-T.; Olmstead, M. M. JACS 1992, 114, 1800.
15. Banks, M. R.; Cadogan, J. I. G.; Dawson, I. M.; Gosney, I.; Grant, K. J.; Gaur, S.; Hodgson, P. K. G.; Stevenson, D. E. Chromatographia 1992, 34, 48.
16. (a) Oppolzer, W.; Moretti, R.; Thomi, S. TL 1989, 30, 5603. (b) Oppolzer, W.; Kingma, A. J. HCA 1989, 72, 1337. (c) Oppolzer, W.; Wills, M.; Starkemann, C.; Bernardinelli, G. TL 1990, 31, 4117.
17. Misra, H. K.; Virzi, F.; Hnatowich, D. J.; Wright, G. TL 1989, 30, 1885.
18. Lucas, H.; Basten, J. E. M.; van Dinther, Th. G.; Meuleman, D. G.; van Aelst, S. F.; van Boeckel, A. A. T 1990, 46, 8207.
19. Dussault, P.; Lee, I. Q. JOC 1992, 57, 1952.
20. Hung, R. R.; Straub, J. A.; Whitesides, G. M. JOC 1991, 56, 3849.

Frederick G. West & John A. Bender

University of Utah, Salt Lake City, UT, USA



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