[109669-49-0]  · C10H24O2  · (MW 166.22)

(reagent used for the protection of vicinal diols)

Physical Data: mp 47-49 °C.

Solubility: soluble in most organic solvents.

Form Supplied in: colorless crystalline compound; available from Fluka, Aldrich.

Purification: recrystallization from petroleum ether.

Handling, Storage, and Precautions: store below -18 °C under inert atmosphere.

Protection of Vicinal Diols

3,3,4,4-Tetrahydro-6,6-bis(2H-pyran) (bis-DHP) complements the vicinal diol protecting ability of 1,1,2,2-tetramethoxycyclohexane with high level of selectivity and stability. The products formed are designated as dispiroketals (dispoke, 1,8,13,16-tetraoxadispiro[]hexadecane) and are quite stable. The dispiroketal formation is normally catalyzed by camphorsulfonic acid (CSA) and the protecting group can be removed hydrolytically under acidic conditions, preferably by transacetalization with ethylene glycol.1 The selective protection of a vicinal diol in the presence of a 1,3-diol is elegantly shown in the reaction of bis-DHP with (S)-butane-1,2,4-triol to give a single stereoisomer (1).2

The stability of the dispoke group was demonstrated in subsequent reactions carried out on the protected derivative.2 Similarly, reactions at the keto group are carried out with the glycolic acid protected dispiroketal without affecting the protecting group.3 The dispoke protection has also been extended to 1,2-dithiols.4

Reaction of bis-DHP with (S)-lactic acid gave the major diasteromer with the methyl group in the equatorial position (2).5

Alkylation of this product with various electrophiles takes place with high stereoselectivity. The deprotection of the alkylated compounds afford substituted products with control of the a-stereocenters. Similarly, several other reactions can be carried out with the dispoke protected lactic acid, mainly under stable basic conditions.6

The dispoke protection strategy is found to be useful in preparing the optically active dinitrile from dispoke protected L-(+)-dimethyl tartarate via the iodinated product (3).7 This dinitrile is used in the synthesis of a chiral magnesium porpyrazine for use as a catalyst for the asymmetric epoxidation of styrene.

A functionalized bis-DHP unit is used as a chiral auxiliary for asymmetric Michael additions which proceed with a high degree of stereoselectivity (4).8

Protection of Vicinal Diols in Carbohydrates

Bis-DHP reacts with the hexapyranosides of fuco, arabino, rhamno, lyxo, and manno series in medium polar solvents in the presence of an acid catalyst (preferably CSA) to give the protected diequatorial diol in all cases (5).4,9 More polar solvents cause decomposition of bis-DHP.

As is also the case with 1,1,2,2-tetramethoxycyclohexane, bis-DHP suffers from the inability to achieve regiocontrolled protection of polyols having a multi set of 1,2-trans diequatorial diols, e.g. a-D-glucopyranoside, from which mixtures of dispoke protected derivatives result.10 The low yield of 39% under standard conditions could be improved to 68% by triphenylphosphine/hydrogen bromide complex as catalyst in DMF as solvent (6).10

Dispoke protected glucosides have been used as acceptors in glycosidation reactions. Thus, the disaccharide shown in 7 has been prepared in 82% yield in an a:b ratio of 5:2 which is further transformed to a trisaccharide.11

Although the dispoke protecting group can be cleaved under acidic conditions, it is possible to introduce another protecting group under acidic conditions if very mild conditions are employed (8).12

Related Reagents.

Benzaldehyde dimethyl acetal [1125-88-8]; butane-2,3-dione, cyclohexane-1,2-dione [765-87-7]; 2,2,3,3-tetramethoxybutane [109669-49-0]; 1,1,2,2-tetramethoxycyclohexane [176798-33-7].

1. Ley, S. V.; Leslie, R.; Tiffin, P. D.; Woods, M., Tetrahedron Lett. 1992, 33, 4767.
2. Ley, S. V.; Woods, M.; Zanotti-Gerosa, A., Synthesis 1992, 52.
3. Fujita, M.; Lainé, D.; Ley, S. V., J. Chem. Soc., Perkin Trans 1 1999, 1647.
4. Ley, S. V.; Downham, R.; Edwards, P. J.; Innes, J. E.; Woods, M., Contemp. Org. Synth. 1995, 2, 365.
5. (a) Downham, R.; Kim, K. S.; Ley, S. V.; Woods, M., Tetrahedron Lett. 1994, 35, 769. (b) Boon, G.-J.; Downham, R.; Kim, K. S.; Ley, S. V.; Woods, M., Tetrahedron 1994, 50, 7157.
6. Zhang, D.; Bleasdale, C.; Golding, B. T.; Watson, W. P., Chem. Commun. 2000, 1141.
7. Hachiya, S.-I.; Cook, A. S.; Williams, B. G.; Montalban, A. G.; Barrett, A. G. M.; Hoffman, B., Tetrahedron 2000, 56, 6565.
8. Bezuidenhoudt, B. C. B.; Castle, G. H.; Innes, J. E.; Ley, S. V., Recl. Trav. Chim. Pays-Bas 1995, 114, 184.
9. Ley, S. V.; Leslie, R.; Tiffin, P. D.; Woods, M., Tetrahedron Lett. 1992, 33, 4767.
10. Hughes, A. B.; Ley, S. V.; Priepke, H. W. M.; Woods, M., Tetrahedron Lett. 1994, 35, 773.
11. (a) Boons, G.-J.; Grice, P.; Leslie, R.; Ley, S. V.; Yeung, L. L., Tetrahedron Lett. 1993, 34, 8523. (b) Grice, P.; Ley, S. V.; Pietruszka, J.; Osborn, H. M. I.; Priepke, H. W. M.; Warriner, S. L., Chem. Eur. J. 1997, 3, 431.
12. Andrews, C. W.; Rodebaugh, R.; Fraser-Reid, B., J. Org. Chem. 1996, 61, 5280.

Thomas Ziegler, Lakshminarayanapuram R. Subramanian & Gregor Lemanski

University of Tübingen, Tübingen, Germany

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.