Highly efficient cyanosilylation of aldehydes and ketones under microwave, solvent-free, and Lewis acid-free conditions

Article abstract of DOI:10.1080/00397910701316185

The addition of TMSCN to aldehydes and ketones under microwave irradiation in the absence of any Lewis or Bronsted acid and solvent yielded the corresponding cyanohydrins in good yields in short reaction times (less than 30 min). Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701316185

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Highly Efficient Cyanosilylation of Aldehydes
and Ketones under Microwave, Solvent‐Free,
and Lewis Acid–Free Conditions
Hirokazu Iida a , Hiroshi Hamana a & Kiyoshi Matsumoto a
a Faculty of Pharmacy , Chiba Institute of Science , Choshi, Chiba, Japan
Published online: 30 Jun 2007.
To cite this article: Hirokazu Iida , Hiroshi Hamana & Kiyoshi Matsumoto (2007) Highly Efficient
Cyanosilylation of Aldehydes and Ketones under Microwave, Solvent‐Free, and Lewis Acid–Free Conditions,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
37:11, 1801-1805, DOI: 10.1080/00397910701316185
To link to this article: http://dx.doi.org/10.1080/00397910701316185
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Synthetic Communicationsw, 37: 1801–1805, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701316185
Highly Efficient Cyanosilylation of
Aldehydes and Ketones under Microwave,
Solvent-Free, and Lewis Acid–Free
Conditions
Hirokazu Iida, Hiroshi Hamana, and Kiyoshi Matsumoto
Faculty of Pharmacy, Chiba Institute of Science, Choshi, Chiba, Japan
Abstract: The addition of TMSCN to aldehydes and ketones under microwave
irradiation in the absence of any Lewis or Brønsted acid and solvent yielded the corre-
sponding cyanohydrins in good yields in short reaction times (less than 30 min).
Keywords: cyanohydrins, microwave irradiation, solvent free
Cyanohydrins can be easily converted into a-hydroxycarbonyl compounds,
b-aminoalcohols, and g-lactones; therefore, these are versatile intermediates
in the context of organic synthesis. For the preparation of cyanohydrins, the
most straightforward method is the addition reaction of carbonyl compounds
with trimethylsilyl cyanide (TMSCN), often followed by treatment with
tetrabutyl-ammonium fluoride (TBAF). Many kinds of protocol have been
proposed for the reaction.[1] Even in 2005, several efficient methods for the
preparation of cyanohydrins were reported; one used ionic liquids
[omium][PF6] as a reaction media in the absence of Lewis acids,[2] and the
others used LiCl[3] and dodecatungestophosphoric acid as Brønsted acid[4] in
solvent-free conditions. In addition, many examples of excellent methods for
synthesis of enantiomerically enriched cyanohydrins were reported quite
recently.[5,6]
Received in Japan June 28, 2006
Address correspondence to Kiyoshi Matsumoto, Faculty of Pharmaceutical
Sciences, Chiba Institute of Science, Choshi, Chiba, Japan. E-mail: kmatsumoto@
cis.ac.jp
1801

1802
H. Iida, H. Hamana, and K. Matsumoto
Reactions performed in a solvent-free environment are becoming more
prevalent in organic chemistry.[7] An increasing need for less hazardous
reaction conditions and environmentally safe procedures has led chemical
synthesis in this direction. Microwave irradiation has been used extensively
in solvent-free reactions. There are mainly three types of solvent-free
reactions: reaction mixtures absorbed onto mineral oxides, phase-transfer
catalysts, and neat reactions.[8]
We have been interested in the organic reactions under unconventional
conditions such as high pressure and microwave irradiation. These reaction
conditions accelerate reaction rates and sometimes yield unexpected
products.[9] No reaction between a ketone and TMSCN in the absence of a
catalyst at high pressure of 0.3 GPa has been reported.[10] Investigating the
effect of microwave irradiations upon this reaction, we found that the
reactions proceeded rapidly without catalysts and solvents. Therefore we
briefly report the results herein.
At first, we investigated the reaction between TMSCN and benzaldehyde
without any solvent or additive. The reaction proceeded smoothly by
microwave irradiation and completed within 5 min. The crude mixture was
subjected to a column chromatography on SiO2 to give the corresponding tri-
methylsilylcyanation adduct 1 (73%) and hydrocyanation adduct 2 (17%). The
reaction using p-anisaldehyde and TMSCN yielded 3 (63%) and 4 (30%)
(isolated yields after silica gel chromatography, not optimized). These
results showed the addition reactions proceeded without Lewis or Brønsted
acids and solvents using microwave irradiation.[4,11–13]
Representative experimental procedure: A mixture of carbonyl compound
(1 mmol) and TMSCN (2 mmol) in the reaction vessel was sealed and heated
for 5 min at 2008C using microwave irradiation (CEM Discover). After
cooling to rt, the mixture was evaporated in vacuo. The crude mixture was
subjected to a short column chromatography on SiO2 using ethyl acetate
and hexane (1:1) as eluent to afford the pure product(s). All isolated
products gave satisfactory spectral data (1H NMR, 13C NMR, MS), which
were in agreement with those reported in the literature.[4,12,13] Selected
spectral data of synthetic cyanohydrins and silylated cyanohydrins: 1: Yield
1
73%, H NMR (CDCl3) d: 0.23 (9H, s), 5.50 (1H, s), 7.24–7.60 (5H, m); 2:
Yield 17%, 1H NMR (CDCl3) d: 2.88 (1H, s), 5.56 (1H, s), 7.24–7.70
1
(5H, m); 3: Yield 63%, H NMR (CDCl3) d: 0.18 (9H, s), 3.80 (3H, s), 5.41
1
(1H, s), 6.85–7.05 (2H, m), 7.30–7.50 (2H, m); 4: Yield 30%, H NMR
(CDCl3) d: 2.64 (1H, d, J ¼ 6.0 Hz), 3.84 (3H, s), 5.49 (1H, d, J ¼ 6.0 Hz),
6.94–6.98 (2H, m), 7.44–7.50 (2H, m).

Preparation of Cyanohydrins under Microwave Irradiation
1803
The microwave-promoted cyanosilylation was amenable to ketones, albeit
for longer reaction times (30 min). A reaction between acetophenone and
TMSCN under the same conditions afforded 5 in moderate yield.[4] 5: Yield
1
62%, H NMR (CDCl3) d: 0.18 (9H, s), 1.86 (3H, s), 7.34–7.80 (5H, m);
13C NMR (CDCl3) d: 0.00, 32.5, 70.6, 120.6, 123.6, 127.5, 127.6, 140.9.
The reactions of TMSCN with aliphatic aldehyde and ketone also proceed
smoothly under the same conditions. For instance, the reaction between
nonanal and TMSCN afforded 6 in 86% yield after SiO2 column chromato-
1
graphy. 6: Yield 86%, H NMR (CDCl3) d: 0.88 (3H, t, J ¼ 5.3 Hz), 1.22–
1.40 (10H, m), 1.45–1.54 (2H, m), 1.80–1.88 (2H, m), 3.23 (1H, d,
J ¼ 4.8 Hz, D2O exchangeable), 4.46 (1H, dd, J ¼ 4.8, 9.6 Hz); 13C NMR
(CDCl3) d: 14.1, 22.6, 24.6, 28.9, 29.1, 29.3, 31.8, 35.1, 61.3, 120.1;[14] In a
similar fashion, the reaction of 2-adamantanone with TMSCN, followed by
treatment of TBAF, afforded 7 in 86% yield.[15]
In conclusion, we disclosed a highly efficient method for the preparation of
cyanohydrins by the reactions between TMSCN and aldehydes or ketones
under microwave irradiation. Without any acid and solvent, the reactions
proceed rapidly, giving the corresponding cyanohydrins and/or trimethylsilyl-
cyanohydrins in good to moderate yields. Further investigations employing
a,b-unasaturated ketones are under way and will be reported in due course.
ACKNOWLEDGMENTS
This work was supported in part by a Grant-in-Aid for Scientific Research
(C, No. 18244120) from the Ministry of Education, Culture, Sports, Science,
and Technology, Japan (to H. H.). This work was also supported in part by a
Grant-in-Aid for Encouragement of Young Scientists (B, No. 16710157)
from the Japan Society for the Promotion of Science (to H. I.). H. I. extends
his gratitude to Sasakawa Scientific Research (Grant Nos. 6–182 and
7–199 K) and Sasakawa Grants for Science Fellows (No. F02–109) from

1804
H. Iida, H. Hamana, and K. Matsumoto
the Japan Science Society for support his research. Finally, special grants from
Chiba Institute of Science (Education and Research Grants in 2004 and 2006 to
K. M. and H. I., respectively) are greatly acknowledged.
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