Reaction of acylsilanes with potassium cyanide: Brook rearrangement under phase-transfer catalytic conditions

Article abstract of DOI:10.1016/S0040-4039(00)00560-8

The reactions of acylsilanes with KCN under liquid-liquid phase-transfer catalytic conditions proceeded smoothly via the Brook rearrangement to produce O-silylated cyanohydrin derivatives in excellent yields. We also found that α-cyano carbanions generate

Full text of DOI:10.1016/S0040-4039(00)00560-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 4169–4172
Reaction of acylsilanes with potassium cyanide: Brook
rearrangement under phase-transfer catalytic conditions
Kei Takeda ∗ and Yuji Ohnishi
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194,
Japan
Received 15 March 2000; accepted 31 March 2000
Abstract
The reactions of acylsilanes with KCN under liquid–liquid phase-transfer catalytic conditions proceeded
smoothly via the Brook rearrangement to produce O-silylated cyanohydrin derivatives in excellent yields.
We also found that α-cyano carbanions generated by the Brook rearrangement in the reaction of (β-
(trimethylsilyl)acryloyl)silane 7 can undergo alkylation at the γ-position and that in the reaction of β-
bromoacylsilane 14 intramolecular alkylation occurs to afford cyclopropanone cyanohydrin derivative 16. © 2000
Elsevier Science Ltd. All rights reserved.
Keywords: cyanides; cyanohydrins; cyclization; rearrangements; silicon and compounds.
Reactions of acylsilanes with nucleophiles have attracted considerable attention because of the unique
transformation, including the Brook rearrangement, which allows the carbonyl group to serve as a 1,1-
dipole.1,2 We became interested in the reaction of acylsilanes with a cyanide ion in connection with our
ongoing investigation directed to the development of Brook rearrangement-mediated reactions.3 Since
the Brook rearrangement is facilitated by carbanion-stabilizing groups,2 we reasoned that the reaction of
acylsilanes with a cyanide ion would be more synthetically useful if the ion could be nucleophilic enough
to generate an appropriate concentration of a carbanion for the Brook rearrangement in the reaction with
acylsilanes. To the best of our knowledge, there has been only one report, that by Reich, on the reaction of
acylsilanes with a cyanide ion.4 We decided to try the reaction of acylsilanes with KCN in a liquid–liquid
two-phase system under phase-transfer conditions. One of our interests was also to see whether the
Brook rearrangement can occur in the presence of water or whether it is intercepted by water to give
an α-silylcarbinol, because it is known that acylsilanes are cleaved by dilute alkaline solutions to give
aldehydes via the attack of a hydroxide ion at the carbonyl carbon5 and, to our knowledge, there has been
no report on the occurrence of the Brook rearrangement in α-hydroxysilanes under aqueous conditions.
When β-alkyl substituted acryloylsilanes 16 were treated with KCN in the presence of n-Bu4NBr in
CH2Cl2–H2O, O-silylated cyanohydrin derivatives 4 were obtained (Table 1).7,8 The use of n-Bu4PBr
∗
Corresponding author. Tel: +81-76-434-7526; fax: +81-76-434-5049; e-mail: takedak@ms.toyama-mpu.ac.jp (K. Takeda)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00560-8
tetl 16839

4170
as a PTC gave a better result. In both cases, no α-silylcarbinol arising from protonation of 2 before the
Brook rearrangement was detected.
Table 1
The almost same result was obtained when the reaction was performed with benzoylsilane 5a and
acylsilanes 5b,c9 (Table 2).
Table 2
The fact that no α-silylcarbinol was detected suggests that an intramolecular nucleophilic attack of the
oxyanion on silicon in adduct 2 to lead to the pentavalent silicon species 3 is faster than the protonation
of the oxyanion by water or that the reaction proceeds via a concerted process involving 3.
In the reaction of the β-alkyl-substituted acryloylsilane 1, no allylic rearrangement to lead to the
formation of enol silyl ethers was observed. We envisaged that the introduction of an anion-stabilizing
group at the β-position in 1 causes the allylic rearrangement to produce a γ-anion derivative of α-
siloxyacrylonitrile. To test this possibility, we examined the reaction of (β-(trimethylsilyl)acryloyl)silane
710,3a with KCN. Under the same conditions employed for 1, we obtained α-siloxyacrylonitrile 9
(Z:E=2.4:1), a product arising from the Brook rearrangement followed by an allylic rearrangement
of a generated carbanion, β-silylpropanoic acid 10, a hydrolysis product of 9, and 11, the Brook
rearrangement product (Scheme 1).
Scheme 1.

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The above results led us to investigate the reaction of 7 with KCN under non-aqueous conditions in
the presence of an electrophile and a PTC that would allow the introduction of substituents on the α-
or γ-position of α-siloxyacrylonitriles. We examined the reactions of 1 and 7 with KCN using methyl
iodide and 18-crown-6 as an electrophile and a PTC, respectively. Whereas the reaction of 1 resulted
in recovery of the starting material, methylated product 12 was obtained in 65% yield together with
protonated derivative 13 from the reaction of 7 (Scheme 2). The Z geometries of 12 and 13 were assigned
on the basis of results of NOESY experiments, and the exclusive formation of the Z derivative was
attributed to the coordination of the allylic anion to the silicon atom.
Scheme 2.
Finally, intramolecular alkylation11 of the silyl-protected cyanohydrin carbanion 15 derived from the
reaction of 14 with KCN in the presence of the crown ether in CH2Cl2 was examined, and the results
are shown in Scheme 3. It is noteworthy that the reaction proceeds at room temperature, because the
base-induced cyclization of O-protected β-chlorocyanohydrin is reported to require heating at 95°C.12
Scheme 3.
In conclusion, we have demonstrated that KCN can serve as a nucleophile in combination with
PTC in the reaction with acylsilanes and thereby provide potentially synthetically useful silyl-protected
cyanohydrin carbanions. Attempts to explore the scope of the reactions are underway.
References
1. For reviews on acylsilanes, see: (a) Brook, M. A. Silicon in Organic, Organometallic, and Polymer Chemistry; John
Wiley & Sons: New York, 2000. (b) Qi, H.; Curran, D. P. In Comprehensive Organic Functional Group Transformations;
Katritzky, A. R.; Meth-Cohn, O.; Rees, C. W.; Moody, C. J., Eds.; Pergamon: Oxford, 1995, pp. 409–431. (c) Cirillo, P. F.;
Panek, J. S. Org. Prep. Proc. Int. 1992, 24, 553–582. (d) Bulman Page, P. C.; Klair, S. S.; Rosenthal, S. Chem. Soc. Rev.
1990, 19, 147–195. (e) Ricci, A.; Degl’Innocenti, A. Synthesis 1989, 647–660.
2. For reviews on the Brook rearrangement, see: (a) Brook, A. G.; Bassindale, A. R. In Rearrangements in Ground and
Excited States; de Mayo, P., Ed.; Academic Press: New York, 1980; pp. 149–221. (b) Brook, A. G. Acc. Chem. Res., 1974,
7, 77–84. Also see: Ref. 1a.
3. (a) Takeda, K.; Nakajima, A.; Takeda, M.; Yoshii, E.; Zhang, J.; Boeckman Jr., R. K. Org. Synth. 1999, 76, 199–213.
(b) Takeda, K.; Ohtani, Y. Org. Lett. 1999, 1, 677–679. (c) Takeda, K.; Tanaka, T. Synlett 1999, 705–708. (d) Takeda,
K.; Nakajima, A.; Takeda, M.; Okamoto, Y.; Sato, T.; Yoshii, E.; Koizumi, T.; Shiro, M. J. Am. Chem. Soc. 1998, 120,
4947–4959. (e) Takeda, K.; Ohtani, Y.; Ando, E.; Fujimoto, K.; Yoshii, E.; Koizumi, T. Chem. Lett. 1998, 1157–1158.
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5. Pietropaolo, D.; Fiorenza, M.; Ricci, A.; Taddei, M. J. Organomet. Chem. 1980, 197, 7–11.
6. Nowick, J. S.; Danheiser, R. L. J. Org. Chem. 1989, 54, 2798–2802. Also see: Ref. 3d.
7. General procedure for the reaction of 1a–e with KCN: A mixture of 1 (0.70 mmol), KCN (50 mg, 0.769 mmol) and n-
Bu4PBr (48 mg, 0.14 mmol) in CH2Cl2–H2O (1:1) (10 mL) was stirred at room temperature for 12 h. The reaction mixture
was poured into half-saturated aqueous NaHCO3 solution (30 mL) and extracted with CH2Cl2 (30 mL×3). Combined
organic phases were washed with saturated brine, dried over K2CO3, and concentrated. The residual oil was subjected to
column chromatography (silica gel, 15 g; elution with hexane–AcOEt=30:1) to give 4.
8. In contrast, reactions of 1 with KCN in organic solvents such as CH2Cl2, MeCN, DMF, or DMSO in the presence or
absence of PTC, or with n-Et4NCN in CH2Cl2 resulted in lower yields of 4 and/or in the recovery of starting material. This
may be partly attributed to the lower stability of the generated carbanion in the solvents. Under the PTC conditions, the
carbanion can be immediately protonated.
9. Compound 5c was prepared by the reaction of acryloylsilane10 with MeOH in the presence of p-TsOH.
10. Reich, H. J.; Kelly, M. J.; Olson, R. E.; Holtan, R. C. Tetrahedron 1983, 39, 949–960.
11. For the formation of cyclopropane derivatives by the reaction of β-chloroacylsilane and phenyllithium followed by the
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12. Stork, G.; Depezay, J. C.; d’Angelo, J. Tetrahedron Lett. 1975, 389–392.