[181208-42-4]  · C25H27LiO4SSi  · (458.08)

(oxiranyllithium; oxiranyl anion; nucleophilic epoxide; acyl anion equivalent; epoxy sulfone)

Solubility: soluble in THF, diethyl ether.

Preparative Methods: prepared by lithiation of (1R,2S)-1-phenylsulfonyl-2-{[(tert-butyldiphenyl)silyl]oxymethyl}oxirane (1, [a]D +55.9 °, c 1.0, CHCl3) (1.0 equiv) in THF (0.15 M solution) with n-BuLi (1 equiv, 1.6 M solution in hexane) in the presence of DMPU or hexamethylphosphoramide (HMPA) (3.0 equiv) at -100°C under argon. Deprotonation is completed within a few minutes (eq 1).1

Handling, Storage, and Precautions: the oxiranyllithium is very unstable, even at -100°C under argon, and should be reacted with electrophiles immediately. The reagent is also conformationally unstable and slowly isomerizes to the trans-isomer when addition of an electrophile is delayed (about 5% isomerization after 20 min at -100°C). Elevated temperatures (>-78°C) cause rapid decomposition.1,2


Although epoxides are widely recognized as extremely versatile synthetic intermediates in view of their electrophilic nature, the reaction of an epoxide as a nucleophile, i.e. an oxiranyl anion, is less common. Recently, cumulative studies on the chemistry of oxiranyl anions have appeared and some aspects of the anions have been discussed.3,4

Preparation of (1R,2S)-1-Phenylsulfonyl-2-{[(tert-butyldiphenyl)silyl]oxymethyl}oxirane and Related Compounds

Epoxidation of (Z)-vinyl sulfone, which is available from the Peterson olefination of (S)-O-pentylideneglyceraldehyde5 and phenyl trimethylsilylmethyl sulfone6 in three steps (40% overall yield), with t-BuOOH/t-BuOK in THF gives epoxy sulfone (eq 2). Deprotection of the ketal group and recrystallization affords an optically pure epoxy diol, which is then treated with sodium periodate followed by sodium borohydride to give an alcohol. Protection of the resulting alcohol as its silyl ether yields (1R,2S)-1-phenylsulfonyl-2-{[(tert-butyldiphenyl)silyl]oxymethyl}oxirane (1).7 Its enantiomer is available in the same manner starting from (R)-isopropylideneglyceraldehyde.8

Racemic epoxy sulfone derivatives are easily prepared from allyl ethers by reaction with sodium p-toluenesulfinate in the presence of iodine followed by treatment with triethylamine, separation of E- and Z-isomers, and epoxidation with t-BuOOH and n-BuLi in THF (eq 3).2

Reaction of Sulfonyl-Stabilized Oxiranyllithiums

Reaction of sulfonyl-stabilized oxiranyllithiums with primary alkyl halides gives acceptable yields of products.1 More reactive alkyl triflates give generally better yields but, due to the instability of oxiranyllithiums, yields are often not reproducible when electrophiles are added to a solution of the preformed oxiranyllithiums. It is recommended that the alkylation reaction be carried out by an in situ trapping method.2 Treatment of a solution of epoxy sulfone (1.0 equiv) and triflate (1.5 equiv) in THF-DMPU (or HMPA) at -100°C under argon with n-BuLi (1.0 equiv) followed by stirring for 30 min affords the coupled product in high yield (eq 4).9 The product can be converted to a tetrahydropyranone derivative by exposure to p-toluenesulfonic acid. The strong electron-withdrawing ability of the sulfonyl group works against the adjacent C-O bond-breaking in an acid-catalyzed epoxide ring-opening process and, consequently, favors the 6-endo mode pathway which yields the tetrahydropyranone after elimination of phenylsulfinic acid. Reaction with a halogenated metal Lewis acid yields a halo ketone instead of a cyclization product (eq 4).10 These reactions demonstrate that the oxiranyllithium reagent serves as a functionalized acyl anion equivalent and a three-carbon building block.

Reiterative application of this protocol has allowed the stereocontrolled construction of polytetrahydropyrans9,10 and polycyclic ethers containing six- and seven-membered rings (eq 5).7

Reaction of the oxiranyllithium with aldehydes is also carried out by an in situ trapping method at very low temperatures in order to avoid decomposition of the reagent. Its applicability to a complex situation has been demonstrated in a synthesis of hemibrevetoxin B (eq 6).11,12 It is noteworthy that deprotonation of 1 by n-BuLi is much faster than butyl addition to the aldehyde.

While alkylation of sulfonyl-stabilized oxiranyllithiums with primary alkyl triflates proceeds in high yield, the reaction towards epoxides is relatively slow (~2 h) and the decomposition of oxiranyllithium is marked, such that it decreases the yield, especially in the case of a Z-isomer (eq 7 and 8).2 Addition of boron trifluoride diethyl etherate promotes this epoxide-epoxide coupling reaction. One of the diastereoisomers of eq 8 has been elaborated via 5-endo cyclization into a marine tetrahydrofuran isolated from a brown alga.13

Related Reagents.

Optically active trisubstituted sulfonyl-stabilized oxiranyllithiums can be generated by deprotonation of the corresponding epoxy sulfones14 (eq 9). Due to the diminished reactivity of the reagents by steric hindrance, the reaction with triflates requires HMPA to obtain a high yield of product (eq 10).12

1. (a) Ashwell, M.; Clegg, W.; Jackson, R. F. W., J. Chem. Soc., Perkin Trans. 1 1991, 897. (b) Dunn, S. F. C.; Jackson, R. F. W., J. Chem. Soc., Perkin Trans. 1 1992, 2863.
2. Mori, Y.; Yaegashi, K.; Iwase, K.; Yamamori, Y.; Furukawa, H., Tetrahedron Lett. 1996, 37, 2605.
3. Satoh, T., Chem. Rev. 1996, 96, 3303.
4. Mori, Y. In Reviews on Heteroatom Chemistry; Oae, S., Ed.; MYU: Tokyo, 1997, Vol. 17, p 183.
5. Schmid, C. R.; Bradley, D. A., Synthesis 1992, 587.
6. Craig, D.; Ley, S. V.; Simpkins, N. S.; Whitham, G. H.; Prior, M. J., J. Chem. Soc., Perkin Trans. 1 1985, 1949.
7. Mori, Y.; Yaegashi, K. Furukawa, H., Tetrahedron 1997, 53, 12917.
8. Schmid, C. R.; Bryant, J. D.; Dowlatzadeh, M.; Philps, J. L.; Prather, D. E.; Schantz, R. E.; Sear, N. L.; Vianco, C. S., J. Org. Chem. 1991, 56, 4056.
9. Mori, Y.; Yaegashi, K.; Furukawa, H., J. Am. Chem. Soc. 1996, 118, 8158.
10. Mori, Y.; Yaegashi, K.; Furukawa, H., Tetrahedron Lett. 1999, 40, 7239.
11. Mori, Y.; Yaegashi, K.; Furukawa, H., J. Am. Chem. Soc. 1887, 119, 4557.
12. Mori, Y.; Yaegashi, K.; Furukawa, H., J. Org. Chem. 1998, 63, 6200.
13. Mori, Y.; Sawada, T.; Furukawa, H., Tetrahedron Lett. 1999, 40, 731.
14. Satoh, T.; Oohara, T.; Ueda, Y.; Yamakawa, K., J. Org. Chem. 1989, 5 4, 3130.

Yuji Mori

Faculty of Pharmacy, Meijo University, Nagoya, Japan

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