Reverse Brook rearrangement of 2-alkynyl trialkylsilyl ether. Synthesis of optically active (1-hydroxy-2-alkynyl)trialkylsilane

Article abstract of DOI:10.1016/S0040-4039(00)01086-8

A new method for the synthesis of optically active α-hydroxyalkynylsilane 3 is described. The key step of the conversion to 3 was the use of the reverse Brook rearrangement of the 2-alkynyl silyl ether 2. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01086-8

Tetrahedron Letters 41 (2000) 6589±6592
Reverse Brook rearrangement of 2-alkynyl trialkylsilyl ether.
Synthesis of optically active
(1-hydroxy-2-alkynyl)trialkylsilane
Kazuhiko Sakaguchi,* Masato Fujita, Hiroyuki Suzuki, Masato Higashino
and Yasufumi Ohfune*
Graduate School of Science, Department of Material Science, Osaka City University, Sugimoto, Sumiyoshi,
Osaka 558-8585, Japan
Received 5 June 2000; revised 22 June 2000; accepted 23 June 2000
Abstract
A new method for the synthesis of optically active a-hydroxyalkynylsilane 3 is described. The key step of
the conversion to 3 was the use of the reverse Brook rearrangement of the 2-alkynyl silyl ether 2. # 2000
Elsevier Science Ltd. All rights reserved.
Keywords: reverse Brook rearrangement; a-hydroxyalkynylsilane; 2-alkynyl silyl ether.
The (1-hydroxy-2-alkynyl)trialkylsilane (a-hydroxyalkynylsilane) derivative, possessing a chiral
a-hydroxysilane group convertible to an aldehyde or a carboxylic acid, has received considerable
attention owing to its potential utility as a building block in organic synthesis.1 However,
methodology for its preparation has been limited to the use of a nucleophilic addition reaction,
i.e. addition of an alkynyl anion to trialkylsilylformaldehyde.2 In this report, we wish to describe
an ecient entry to the synthesis of (1-hydroxy-2-alkynyl)trialkylsilane 3 by means of reverse
Brook rearrangement of 2-alkynyl trialkylsilyl ether 2.
ꢀ1†
* Corresponding author. Fax: +00 81 6 6605 3153; e-mail: sakaguch@sci.osaka-cu.ac.jp
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01086-8

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Treatment of a 2-alkenyl silyl ether with a strong base is well known to undergo the reverse
Brook rearrangement to give (1-hydroxy-2-alkenyl)trialkylsilane,3 while no successful example
regarding the reverse Brook rearrangement employing 2-alkynyl silyl ether has been reported to
date, due probably to the instability of the 2-alkynylalkoxylithium intermediate B (Eq. (1)). In
fact, treatment of the propargyl silyl ether 2a with n- or tert-BuLi resulted in a complete recovery
of the starting material. On the other hand, the use of 3 equiv. of sec-BuLi was found to e€ect the
desired rearrangement to give 3a in 16% yield,4 apparently indicating the presence of an
equilibrium between A and B.5
Encouraged by this ®nding, we attempted to improve its yield. Finally, the yield was optimized
to 70% when unprotected propargyl alcohol (1a) was treated with the following sequence of
reactions in one pot (method A): (1) TBDMSCl and n-BuLi in THF; (2) 3 equiv. of sec-BuLi at
^45ꢁC for 22 h; and (3) acetic acid in THF at ^78ꢁC (Table 1, entry 1).5,6 This method was applied
to other 2-alkyn-1-ols (1b±d). The reaction of 2-butyn-1-ol (1b) using 1.2 equiv. of n-BuLi for the
rearrangement step provided 3b in 86% yield (entry 2), while the use of the isolated TBDMS
ether 2b (method B) a€orded the same product in 45% yield (entry 7), where the yield was
improved to 78% by using 3 equiv. of n-BuLi (entry 8). 2-Octyn-1-ol (1c) using TMSCl and tert-
BuLi7 a€orded the a-hydroxytrimethyl-silane 3c in 45% yield (entry 4). In this case, method A
was slightly superior to method B (35%, entry 9) in terms of yield. Next, we examined these
Table 1
The reverse Brook rearrangement of 2-alkylnyl trialkylsilyl ether

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methods for the conversion of the secondary propargyl alcohol 1d or its silyl ether 2d into the
corresponding a-substituted-a-hydroxysilane 3d, which has a sterically crowded tertiary hydroxy
group. Method A using TMSCl and tert-BuLi was quite e€ective for this conversion to give 3d in
67% yield (entry 10), together with the allenol ether 4d8 (31%, vide infra).9 Thus, the reverse
Brook rearrangement was found to be an ecient method for the preparation of various types of
the (1-hydroxy-2-alkynyl)trialkylsilanes 3a±d.
One question arose from the above results, namely, why did direct treatment of the silyl ether 2
with the base (method B) result in a signi®cant decrease in the yields of the a-hydroxysilane 3 in
comparison with its one-pot preparation (method A) where LiCl, produced at the silylation step,
existed in the reaction? To understand the role of LiCl, the following experiments were
performed: (1) the use of TBDMSOTf instead of TBDMSCl for method A; and (2) the addition
of LiCl to method B. The reaction of 1b using TBDMSOTf gave 3b in 32% yield which was much
lower than that obtained using TBDMSCl (entry 3). Addition of LiCl (1±3 equiv.) to the reaction
of the silyl ethers 2a±c resulted in a slight increase in the yields, respectively (entries 6±9), which
were, however, still lower than those obtained by method A. It is noted that none of the allenol
ethers 4a±c were by-produced by the addition of LiCl. These results indicate that LiCl plays an
important role to obtain better yields in both methods, and prevents the formation of the allenol
ethers in method B, which would be produced through an intermediate such as A in Eq. (1).
However, the real role of LiCl in the present reaction is not clearly understood at this stage,
although it has been reported that lithium halides a€ect the equilibrium of the Brook rearrangement.8c
The conversion of the resulting 3a±c into their optically active forms was accomplished as
shown in Scheme 1. Jones oxidation of 3a gave the silyl ketone 5a in good yield. Enantioselective
reduction of 5a with 5 equiv. of BH3 in the presence of 2 equiv. of (S)-oxazaborolidine 610
a€orded the optically active (1-hydroxy-2-alkynyl)trialkylsilane (S)-3a11 (57% yield, >95%
ee).12,13 The a-hydroxysilane (S)-3b11 (>95% ee)12 was synthesized in the same manner. On the
other hand, the a-hydroxysilane 3c was converted to the silyl ketone 5c by Swern oxidation
because of its instability under the acidic conditions. Successful conversion of 5c into the optically
active a-hydroxysilane (R)-3c11 (>95% ee)12 using (^)-B-chloro diisopinocamphenylborane
(7, (^)-DIP-Cl)14 has been reported.1,15
Scheme 1.
In summary, we have found that the reverse Brook rearrangement is a useful method for the
conversion of the 2-alkynyl trialkylsilyl ether 2 into the (1-hydroxy-2-alkynyl)trialkylsilane 3,
whose optically active form was prepared by oxidation and subsequent enantioselective
reduction.

6592
References
1. Sakaguchi, K.; Mano, H.; Ohfune, Y. Tetrahedron Lett. 1998, 39, 4311±4312.
2. Linderman, R. J.; Suhr, Y. J. J. Org. Chem. 1988, 53, 1569±1572.
3. (a) Brook, A. G. Acc. Chem. Res. 1974, 77±84. (b) Danheiser, R. L.; Fink, D. M.; Okano, K.; Tsai, Y.-M.;
Szczepanski, S. W. J. Org. Chem. 1985, 50, 5393±5396. (c) Danheiser, R. L.; Fink, D. M.; Okano, K.; Tsai, Y.-M.;
Szczepanski, S. W. In Org. Synth. Coll. Vol. VIII; John Wiley & Sons: New York, 1993; pp. 501±505.
4. When a nearly stoichiometric amount of the base was used for method B, the yields of 3a±d decreased and a
signi®cant amount of 2a±d was recovered, respectively.
5. The yields of 3a decreased when the reaction (entry 1) was quenched at elevated temperature (^45ꢁC, 13% of 3a
and 13% of 4a; 0ꢁC, 9% of 3a and 17% of 4a). The corresponding silyl ether 2a was not recovered at all.
6. Representative experimental procedure for the reverse Brook rearrangement by method A: To a solution of 1b
(10.0 g, 142.7 mmol) in THF (180 mL), was added n-BuLi in n-hexane (149.8 mmol) at ^78ꢁC, and the mixture was
stirred at 0ꢁC for 30 min. To the solution was added a solution of TBDMSCl (22.6 g, 149.8 mmol) in THF (30 mL)
at ^78ꢁC. After stirring at room temperature for 4 h, n-BuLi (171.2 mmol) in n-hexane at ^78ꢁC was added to the
solution dropwise, and the mixture was stirred at ^45ꢁC for 2 h. The reaction was quenched by 10% AcOH in
THF at ^78ꢁC. The mixture was extracted with Et2O, and the organic phase was washed with saturated NaHCO3
and brine, dried over MgSO4, and concentrated in vacuo. The residue was puri®ed by column chromatography on
silica gel (n-hexane/Et2O, 30/1) to give 3b (22.5 g, 86%) as a colorless oil.
7. The use of n-BuLi for the reaction of the TMS ether 2c or 2d resulted in cleavage of the TMS group.
8. Preparation of silyl allenol ether from (1-substituted-1-hydroxy-2-alkynyl)trimethylsilane, see: (a) Kuwajima, I.;
Kato, M. Tetrahedron Lett. 1980, 21, 623±626. (b) Reich, H. J.; Olson, R. E.; Clark, M. C. J. Am. Chem. Soc.
1980, 102, 1423±1424. (c) Reich, H. J.; Eisenhart, E. K.; Olson, R. E.; Kelly, M. J. J. Am. Chem. Soc. 1986, 108,
7791±7800.
9. Treatment of the TBDMS-substituted analogue of 2d with n-, sec-, or tert-BuLi resulted in a complete recovery of
the starting material.
10. (a) Corey, E. J.; Bakshi, R. K.; Shibata, K. P. J. Am. Chem. Soc. 1987, 109, 5551±5553. For reviews, see: (b) Singh, V. K.
Synthesis 1992, 605. (c) Wallbaum, S.; Martens, J. Tetrahedron: Asymmetry 1992, 3, 1475±1504. (c) Deloux, L.;
Srebnik, M. Chem. Rev. 1993, 93, 763±784.
25
D
25
D
11. (S)-3a: Colorless oil, ‰ꢀŠ ^75.6ꢁ (c 0.62, CHCl3, >95% ee); (S)-3b: Colorless oil, ‰ꢀŠ ^80.0ꢁ (c 1.20, CHCl3,
25
D
>95% ee); (R)-3c: Colorless oil, ‰ꢀŠ +78.5ꢁ (c 2.00, CHCl3, >95% ee).
1
12. The optical purity and absolute con®guration of 3a±c were determined by the modi®ed Mosher method using H
NMR. Ohtani, I.; Kusumi, T.; Kashman, Y.; Kakisawa, H. J. Am. Chem. Soc. 1991, 113, 4092±4093.
25
D
13. The TIPS-substituted analogue of (S)-3a (‰ꢀŠ ±66.0ꢁ (c 0.89, CHCl3, >95% ee)12 was also prepared (64%) using
oxazaborolidine 6 from its racemic form which was prepared from 1a using TIPSCl by the reverse Brook
rearrangement (70%, method A).
14. (a) Sonderquist, E. J.; Anderson, C. L.; Miranda, E. I.; Rivera, I. Tetrahedron Lett. 1990, 31, 4677±4680. (b) Dahr, R. K.
Aldrichimica Acta 1994, 27, 43±51.
15. (^)-DIPCl (7) was also e€ective for the enantioselective reduction of 5b to give (R)-3b (82% yield, >95%) ee.12