[15933-59-2]  · C4H15NSi2  · 1,1,3,3-Tetramethyldisilazane  · (MW 133.38)

(intramolecular hydrosilation of allyl alcohols, homoallyl alcohols, and homopropargyl alcohols for the regio- and stereoselective synthesis of polyols)

Physical Data: bp 99-100 °C; n20D 1.4040; d 0.752 g cm-3.

Solubility: common organic solvents.

Form Supplied in: neat liquid.

Handling, Storage, and Precautions: moisture sensitive but no special precautions necessary for handling in the air for a short period of time. May be stored under nitrogen in a tightly capped bottle in a refrigerator. Use in a fume hood.

Intramolecular Hydrosilation.1,2

Allyl and homoallyl alcohols are transformed into 1,3-diols in a highly regio- and stereoselective fashion via intramolecular hydrosilation followed by oxidative cleavage of the silicon-carbon bonds by Hydrogen Peroxide, which proceeds with complete retention of configuration at carbon (eqs 1 and 2).3,4

Thus, an alcohol is converted into a hydrodimethylsilyl ether by treatment with 1,1,3,3-tetramethyldisilazane in the absence or presence of a catalytic amount of ammonium chloride as a promoter. The ammonia produced in this reaction and the excess disilazane must be removed prior to the hydrosilation step (see also Chlorodimethylsilane and N,N-Diethylaminodimethylsilane. The intramolecular hydrosilation can be achieved by using a platinum or rhodium catalyst (<=1 mol %) such as acidic H2PtCl6.6H2O in i-PrOH (Speier's catalyst) or THF, neutral Pt[{(CH2=CH)Me2Si}2O]2 in xylene, or Chlorotris(triphenylphosphine)rhodium(I) (Wilkinson's catalyst). After the reaction, the catalyst, which causes a rapid decomposition of hydrogen peroxide in the subsequent oxidation step, must be removed by stirring the mixture with crystalline EDTA.2Na or activated carbon followed by filtration.2 The oxidative cleavage of the organosilane intermediate usually proceeds smoothly at room temperature under the standard conditions shown in the following examples.

The reaction of terminal allyl alcohols proceeds in a 5-endo fashion to give five-membered ring compounds regioselectively and stereoselectively. Subsequent oxidation affords 2,3-syn-1,3-diols preferentially, regardless of the nature of the catalyst (eq 1).5 The stereoselectivity increases with increased bulkiness of the allylic substituent R1 and the nature of the alkene substituent R2 (see below).5 5-Exo type cyclization occurs with homoallyl alcohols to form five-membered heterocycles and 1,3-diols after oxidation. Two chiral centers are produced in this reaction. The 2,3-relationship (anti) is controlled by the allylic substituent, while the 3,4-relationship is determined by the stereochemistry of the alkene; the hydrosilation occurs by cis addition of Si-H to the alkene (eq 2).5b

This methodology has been applied to the construction of a variety of stereoisomers of polypropionate skeletons, as exemplified by the formation of a tetraol from a symmetrical bis-allyl alcohol by a sequence involving three intramolecular hydrosilation-oxidation steps (eq 3).5b

Extremely high stereoselectivity has been attained in the intramolecular hydrosilation of a-hydroxy enol ethers, leading to 1,2,3-triol derivatives with 2,3-syn stereochemistry (eq 4).6 It has been pointed out, however, that the stereoselectivity largely depends upon the nature of the catalyst, Pt or Rh, and the presence or absence of the disilazane in the Pt case (eq 5).7

The intramolecular hydrosilation of homopropargyl alcohols also proceeds in a 5-exo manner to form five-membered cyclic vinylsilanes exclusively. Subsequent oxidation affords a b-hydroxy ketone (eq 6).8 The vinylsilane also undergoes a Pd-catalyzed cross-coupling reaction with aryl or alkenyl halides stereoselectively (eq 6).9 The intramolecular hydrosilation thus provides an efficient methodology for the regio- and/or stereoselective functionalization and carbon-carbon bond formation of the alkyne moiety in homopropargyl alcohol.

While the five-membered cyclic alkoxysilane moiety has been found to tolerate a wide range of chemical transformations (OsO4 oxidation, Swern oxidation, Horner-Emmons alkenation, protection conditions such as Tr/py+ BF4- and MeI/NaH, and catalytic hydrogenation), the carbon-silicon bond can be cleaved efficiently by Tetra-n-butylammonium Fluoride in DMF (eq 7).10

The intramolecular hydrosilation of allyl alcohols containing an ester group at the terminal carbon proceeds in a 5-endo fashion to form the five-membered cyclic products with modest stereoselectivity. The silyl group a to the carbonyl group is readily cleaved by a fluoride ion in protic solvents (eq 8).11

Catalytic asymmetric intramolecular hydrosilation of allyl alcohols has been achieved by using Chlorodiphenylsilane12 or 1-chloro-1-silacyclohexane13 as the silylating agent.

1. Tamao, K. J. Synth. Org. Chem. Jpn. 1988, 46, 861.
2. Tamao, K.; Nakagawa, Y.; Ito, Y. OS 1995, in press.
3. Tamao, K.; Ishida, N.; Tanaka, T.; Kumada, M. OM 1983, 2, 1694.
4. Colvin, E. W. COS 1991, 7, 641.
5. (a) Tamao, K.; Tanaka, T.; Nakajima, T.; Sumiya, R.; Arai, H.; Ito, Y. TL 1986, 27, 3377. (b) Tamao, K.; Nakajima, T.; Sumiya, R.; Arai, H.; Higuchi, N.; Ito, Y. JACS 1986, 108, 6090. (c) Anwar, S.; Davis, A. P. Proc. R. Ir. Acad. 1989, 89B, 71.
6. Tamao, K.; Nakagawa, Y.; Arai, H.; Higuchi, N.; Ito, Y. JACS 1988, 110, 3712.
7. (a) Curtis, N. R.; Holmes, A. B.; Looney, M. G. TL 1992, 33, 671. (b) Curtis, N. R.; Holmes, A. B. TL 1992, 33, 675.
8. Tamao, K.; Maeda, K.; Tanaka, T.; Ito, Y. TL 1988, 29, 6955.
9. Tamao, K.; Kobayashi, K.; Ito, Y. TL 1989, 30, 6051.
10. Hale, M. R.; Hoveyda, A. H. JOC 1992, 57, 1643.
11. Denmark, S. E.; Forbes, D. C. TL 1992, 33, 5037.
12. Tamao, K.; Tohma, T.; Inui, N.; Nakayama, O.; Ito, Y. TL 1990, 31, 7333.
13. Bergens, S. H.; Noheda, P.; Whelan, J.; Bosnich, B. JACS 1992, 114, 2121.

Kohei Tamao

Kyoto University, Japan

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