A novel synthetic approach to β-arylselenenyl tertiary alcohols by the one-pot reaction of chloromethyl selenides and ketones promoted by samarium diiodide

Article abstract of DOI:10.1055/s-1998-1930

At ambient temperature, β-arylselenenyl tertiary alcohols can be conveniently synthesized with samarium diiodide, chloromethyl selenides and ketones by one-pot method in high yields.

Full text of DOI:10.1055/s-1998-1930

November 1998
SYNLETT
1191
A Novel Synthetic Approach to β-Arylselenenyl Tertiary Alcohols by the One-Pot Reaction of
Chloromethyl Selenides and Ketones Promoted by Samarium Diiodide
Xian Huang* and De-Hui Duan
Department of Chemistry, Hangzhou University, Hangzhou Zhejiang 310028, P.R.China
Fax: 86 571 8807077; E-mail: huangx@public.hz.zj.cn
Received 31 July 1998
Abstract: At ambient temperature, β-arylselenenyl tertiary alcohols can
be conveniently synthesized with samarium diiodide, chloromethyl
selenides and ketones by one-pot method in high yields.
Grignard procedure fails, too. Even in the absence of a proton donor,
chloromethyl selenides are reduced to methyl aryl selenides. The
representative experimental results9 are summarized in Table 1.
β-Hydroxyalkyl selenides are valuable intermediates for the synthesis of
various selenium-free compounds1. They have been reduced to
alcohols, transformed to alkenes, rearranged to ketones and used as the
precursors of epoxides and allyl alcohols. β-Hydroxyalkyl selenides
have been already synthesized by the reaction of α-selenoalkyllithiums
towards aldehydes or ketones2. Another method was by the addition
reaction of phenylselenenyl chloride to olefins followed by hydrolysis3.
Although the former is the most general method, the necessary
selenoacetals can not be easily obtained4, and the preparations and
reactions of α-selenoalkyllithiums are required at low temperature
(usually at -78°C), which causes some inconvenient operation. With
regard to the latter, for the absence of regioselectivity in the addition
reaction, two mixtures are usually obtained, which limited its use. Now
we provide a novel approach to β-arylselenenyl tertiary alcohols, one
important type of β-hydroxyalkyl selenides. Target products are
obtained by a one-pot procedure with chloromethyl arylselenides,
ketones and samarium diiodide under very mild conditions. With a
modified literature5 method, chloromethyl arylselenides can be also
conveniently prepared6 (see Scheme 1).
Table 1
Scheme 1
Recently, applications of samarium diiodide in organic synthesis have
become popular7. Kagan firstly found that as well as being a powerful
reducing agent, SmI2-THF solution could promote efficiently
alkylations of ketones by alkyl halides8. Alkyl iodide, bromide and
sulfonates have achieved satisfactory results. When alkyl chlorides
(even allyl chlorides) were used, long reaction time and low yields were
encountered. However, in our experiments, chloromethyl selenides can
act as an excellent arylselenomethylation agent. At room temperature,
the alkylation reactions are completed over 2-6 hrs in high yields
(usually over 70%). Therefore, the ability of the selenium functional
group to stabilize adjacent carbanions must facilitate greatly the
alkylation reaction. Except for acetophenone, the reaction towards alkyl
ketones and cycloalkylketones can achieve good results by the
simultaneous addition of ketones and chloromethyl selenides to the
samarium diiodide solution of THF. Low yield (30%) of tertiary alcohol
is obtained in the reaction of acetophenone by the above procedure. If
chloromethyl selenide is added prior to the addition dropwise of the
acetophenone solution, the yield can be improved to 60%. The
alkylation of aldehydes is unsuccessful because the direct reduction to
alcohols and/or pinacol coupling dominates the reaction. Attempt of a
In conclusion, we found a novel method for one-pot preparation of β-
hydroxyalkyl selenides. Mild reaction conditions, convenient operation,
available materials and high yields make it attractive.
Acknowledgment: Projects 29493800, 29672008 supported by the
National Natural Science Foundation of China and Laboratory of
Organometallic Chemistry, Shanghai Institute of Organic Chemistry ,
Academia Sinica.
References and Notes
1
Krief, A. Selenium Stabilization; Comprehensive Organic
Synthesis; Trost, B. M. Ed., Pergamon Press: New York; 1990,
Vol. 1, 629.
2
3
Krief, A.; Dumont, W.; Clarembeau, M.; Bernard, G. and Badaoui,
E., Tetrahedron, 1989, 45, 2005.
Toshimitsu, A.; Aoai, T.; Owada, H.; Uemura, S. and Okano, M.,
Tetrahedron, 1985, 41, 5301.

1192
4
LETTERS
SYNLETT
Clarembean, M.; Cravador, A.; Dumont, W.; Hevesi, L; Krief, A.;
Lucchetti, J. and Van Ende, D., Tetrahedron, 1985, 41, 4793.
8
9
Girard, P.; Namy, J. L. and Kagan, H. B., J. Am. Chem. Soc., 1980,
102, 2693.
5
6
Beckwith, A. L. J. and Pigon, P. E., Aust. J. Chem., 1986, 39, 77.
Typical procedure. A SmI2 (2.0mmol) solution of THF(20ml)was
placed in a 50ml two-necked flask, 1mmol of 2-butanone in 5ml
of THF was added, then 1mmol of chloromethyl phenylselenide in
5ml of THF was introduced. Reaction was performed under
nitrogen at room temperature. After 4hrs, the initial blue solution
of SmI2 turned yellow, indicating the end of the reaction. The
mixture was worked up with the dilute HCl(0.1N). Organic
product was extracted twice with ether. The organic layer was
washed with water, sodium thiosulfate, water and brine. After the
solution was dried over MgSO4, solvent was removed. The
product was separated from the residue through preparative TLC
(silica gel)with cyclohexane /ethyl ether (4:1) as eluent to give 2-
The following procedure is typical for the preparation of
chloromethyl arylselenides. A 500ml three-necked flask equipped
with a magnetic bar, a reflux condenser, a nitrogen inlet and a
100ml pressure equalizing addition funnel, was charged with dry
dichloromethane (300ml) and potassium borohydride (4.86g,
90mmol). A diphenyl diselenide (9.4g, 30mmol) suspending
solution of ethanol (75ml) was poured into the funnel. The
reaction flask was stirred and gently refluxed while the
suspending solution was added in batches over two hours. When
the solution lost its yellow colour, stirring was continued for
30mins. The crude mixture was washed with dilute HCl, water,
and brine, then it was dried with MgSO4 and the solvent was
evaporated. Distillation of the residue provided chloromethyl
phenyl selenide (10.3g, 50mmol, 83%) 2a as an almost colourless
oil. 90-92/3mmHg.(Lit.10 63-65/0.1torr). 1H NMR δH (ppm): 4.92
(s, 2H ), 7.20-7.65 (m., 5H).
methyl-1-phenylselenobutan-2-ol 3b (Oil,83%). IR νmax/cm−1
:
3500; 2980; 2940; 1590; 1480; 1440; 1380; 730; 680. 1Η
ΝΜR(CCl4/TMS) δΗ (ppm): 0.89 (t, 3Η, J=7.1Ηz), 1.17 (s, 3Η),
1.43 (q, 2Η, J=7.1Ηz), 1.83 (br s, 1Η), 3.02 (s, 2Η), 7.10-7.60 (m,
5Η). ΜS (m/z, relative intensivity %) (ΕΙ): 244(80Se,100) and
242(78Se,49) (Μ+), 227(35), 172(82), 157(20), 73 (46). Anal.
calcd. for C11H16OSe C%,54.32; Η%,6.63. Found:
C%,54.15;Η%, 7.01.
7
(a) Molander, G. A. and Harris, C. R., Chem. Rev., 1996, 96, 307.
(b) Molander, G. A. and Harris, C. R., Tetrahedron, 1998, 54,
3321. (c) Yamashita, M.; Kitagawa, K.; Ohhara, T.; Iida, Y.;
Masumi, A.; Kawasaki, I. and Ohta, S., Chem. Lett., 1993, 653.
10 Schollkopf, U. and Kuppers, H., Tetrahedron Lett., 1963, 105.