Preparation of α-Arylseleno-substituted Zinc and Copper Organometallics and their Application in the Synthesis of α-Arylselenomethyl Ketones

Article abstract of DOI:10.1039/a708947c

α-Arylseleno-substituted zinc and copper organometallics, prepared by zinc insertion into the carbon-chlorine bond of α-chloromethyl aryl selenides and with CuCN-2LiCl transmetallation to the corresponding copper reagents, react with acyl chlorides to give α-arylselenomethyl ketones based on the formation of a new carbon-carbon bond.

Full text of DOI:10.1039/a708947c

View Article Online / Journal Homepage / Table of Contents for this issue
396 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
1998, 396±397$
Preparation of a-Arylseleno-substituted Zinc and
Copper Organometallics and their Application in the
Synthesis of a-Arylselenomethyl Ketones$
Xian Huang* and De-Hui Duan
Department of Chemistry, Hangzhou University, Hangzhou Zhejiang, 310028, P.R. China
ꢀ-Arylseleno-substituted zinc and copper organometallics, prepared by zinc insertion into the carbon±chlorine bond of
ꢀ-chloromethyl aryl selenides and with CuCN±2LiCl transmetallation to the corresponding copper reagents, react with
acyl chlorides to give ꢀ-arylselenomethyl ketones based on the formation of a new carbon±carbon bond.
Organolithiums bearing
a selenium-stabilized carbanion
Table 1 a-Arylselenomethyl ketones
have played an important role in organic synthesis.1 They
easily convert the selenium group into various other func-
tionalities and allow the synthesis of more complex organo-
selenium compounds with concomitant formation of a new
carbon±carbon bond. However, the high reactivity of these
reagents prohibits the presence of most functional groups
in these organometallics. In addition, the high thermal
instability means that their preparations and reactions can
be carried out only at low temperature (usually 78 8C).
Herein, we report a new approach to a-selenocarbanions of
zinc and copper, which complement the known organo-
lithium reagents.
Reaction Yield
(%)a
Compound
Ar
R
time/h
5a
5b
5c
5d
5e
5f
Ph
Ph
p-MeC6H4
Ph
Ph
p-MeC6H4
Ph
Ph
Me
Ph
p-ClC6H4
p-BrC6H4
Me
4
6
4
4
4
6
6
75
85
80
70
76
83
82
5g
Me[CH2]3CH2
aIsolated yields of pure products.
Knochel et al.2 found that, in the zinc organometallics
undergoing insertion, oxygen and sulfur functional groups
at the a position could not only be tolerated, but also both
atoms could considerably facilitate the insertion of zinc
into a carbon±halide bond. We have now observed that a
selenium atom exerts a similar e€ect and allows insertion
of zinc into an adjacent carbon±chlorine bond. Thus, the
treatment of an a-chloromethyl phenyl selenide 1 with zinc
dust (activated in situ with 1,2-dibromoethane and chloro-
trimethylsilane) in THF at 25 8C for 6 h provides the corre-
phenylseleno group, especially for stereoselective trans-
formation of carbon±carbon double bonds via the well
established syn-elimination process. A selenium functional
group is usually introduced into a molecule by the attack of
electrophilic organoselenium reagents (such as PhSeBr,
PhSeCl) on enols and ketones,5 ole®ns6 or acetylenes,7 or by
the substitution of nucleophilic organoselenium reagents
(such as PhSeNa, PhSeSmI2) for a-halogenated ketones.8 In
addition, the direct insertion of diazomethane into seleno-
esters9 is also a good synthetic method. However all these
methods are founded on the formation of a carbon±
selenium bond. In our experiments the copper organo-
metallics 3 can react smoothly with acyl chlorides 4 to
a€ord a series of a-arylseleno methyl ketones 5 based ®rst
on the formation of a carbon±carbon bond (Scheme 1). The
results are summarized in Table 1.
In conclusion, zinc a-selenocarbanions can be con-
veniently prepared under mild conditions. Besides their high
thermal stability (no decomposition at 25 8C under an inert
atmosphere for 30 h), they can be eciently transmetallated
to zinc±copper reagents, which display an excellent
reactivity toward acyl chlorides a€ording a-arylselenomethyl
ketones depending on the formation of a carbon±carbon
bond.
sponding organozinc chloride
2 in good yield (75%)
(Scheme 1). In contrast, it was found that a-chloroalkyl
alkyl selenides such as chloromethyl butyl selenide do not
insert zinc under the similar conditions. Comasseto et al.3
have reported an a-methylseleno ethenyl zinc organometallic
prepared by insertion of zinc (powder) into a sp2 carbon±
iodine bond. However, its low reactivity to organic electro-
philes and the poor stereoselectivity of the products limited
its application. By the addition of CuCN±2LiCl, organozinc
chlorides 2 can easily be converted into the copper organo-
metallics 3, which can be anticipated to be more useful in
the synthesis of selenium-containing compounds.
a-Phenylseleno carbonyl compounds are important
synthetic intermediates with a wide range of utilities in
organic synthesis.4 They have been used for regioselective
introduction of various functional groups by displacing the
Experimental
1H NMR spectra were recorded in CCl4 on a JEOL PMX 60si
spectrometer using hexamethyldisiloxane (HMDSO) as internal
standard. Chemical shifts are reported as d in units of parts per
million (ppm). IR spectra were obtained on a PE683 spectrometer.
THF was distilled from sodium±benzophenone immediately before
use. Chloromethyl selenides were prepared according to the litera-
tion.10 Acyl chlorides were redistilled prior to use. The remaining
chemicals were obtained from commercial sources. All reactions
were performed under a nitrogen atmosphere.
General Procedure for Preparation of ꢀ-Phenylselenomethylzinc
Chlorides 2.ÐA dry three-necked ¯ask equipped with a magnetic
stirring bar and a thermometer under nitrogen was charged with
zinc dust (0.19 g, 3 mmol) and ¯ushed three times with nitrogen.
1,2-Dibromoethane (0.02 g, 0.1 mmol) in THF (2 ml) was then
added. The resulting zinc suspension was gently heated to boiling
and then cooled again to room temperature. The same activation
process was repeated twice and chlorotrimethylsilane (0.02 g,
Scheme 1 Ar ˆ Ph, p-MeC6H4; R ˆ Ph, p-ClC6H4, p-BrC6H4,
Me, Me[CH2]3CH2
*To receive any correspondence.
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).

View Article Online
J. CHEM. RESEARCH (S), 1998 397
Table 2 Spectral data for compounds 5a±5g (all oils)
Compound
1H NMR
IR
5a a-Phenylselenoacetophenone5c
3.98 (s, 2 H), 7.07±7.52 (m, 8 H),
7.67±7.93 (m, 2 H)
2.13 (s, 3 H), 3.41 (s, 2 H), 7.13±7.63
(m, 5 H)
3085, 2940, 2865, 1685, 1605, 1590,
1485, 1450, 1275, 1010, 715, 700, 685
3080, 2940, 1715, 1585, 1485, 1360,
1230, 1020, 690, 675
3040, 2940, 2860, 1685, 1605, 1590,
1475, 1450, 1275, 1010, 740, 700, 680
5b a-Phenylselenoacetone5c
5c a-(p-Methylphenyl)selenoacetophenone8b 2.24 (s, 3 H), 3.92 (s, 2 H), 6.94, 7.03
(d, 2 H), 7.32±7.46 (m, 5 H), 7.72±7.90
(m, 2 H)
5d p-Chloro-a-phenylselenoacetophenone8b
5e p-Bromo-a-phenylselenoacetophenone8b
5f a-(p-Methylphenyl)selenoacetone9
5g 1-Phenylselenoheptan-2-one5e
3.93 (s, 2 H), 7.10±7.43 (m, 7 H),
7.63±7.85 (m, 2 H)
3.93 (s, 2 H), 7.06±7.65 (m, 9 H)
3080, 2970, 2940, 2870, 1685, 1600,
1580, 1490, 1275, 1090, 1010, 735, 685
3080, 2940, 2860, 1685, 1595, 1485,
1270, 1070, 1000, 750, 680
2.08 (s, 3 H), 2.24 (s, 3 H), 3.35 (s, 2 H), 3080, 2940, 2870, 1715, 1475, 1360,
6.93 (d, 2 H), 7.28 (d, 2 H) 1230, 1035, 740
0.83 (t, 3 H), 1.06±1.77 (m, 6 H), 2.46 2970, 2940, 2880, 1710, 1590, 1485,
(t, 2 H), 3.40 (s, 2 H), 7.06±7.46 (m, 5 H) 1020, 730, 685
0.1 mmol) added. After 10 min of stirring at room temperature,
ꢀ-chloromethyl phenyl selenide (0.21 g, 1 mmol) in THF (2 ml) was
added dropwise over 10 min. The mixture was stirred for 6 h at
25 8C. The reaction was monitored and the yield estimated by 1H
NMR analysis of hydrolysed aliquots. After 6 h the peak at ꢁ 4.77
Received, 12th December 1997; Accepted, 7th April 1998
Paper E/7/08947C
References
(s, PhSeCH2Cl) disappeared and that at
ꢁ 2.23 (s, PhSeCH3)
1 A. Krief, Comprehensive Organic Synthesis, ed. B. M. Trost,
Pergamon Press, New York, 1991, vol. 1, p. 629.
reached a maximum, approximately 75% yield. The excess of zinc
was allowed to settle and the resulting clear solution was ready to
use for further transformation.
2 (a) P. Knochel, T.-S. Chou, H. G. Chen, M. C. P. Yeh and M. J.
Rozema, J. Org. Chem., 1989, 54, 5202; (b) T.-S. Chou and
P. Knochel, ibid. 1990, 55, 4791; (c) S. Achyutha Rao, C. E.
Tucker and P. Knochel, Tetrahedron Lett., 1990, 31, 7575;
(d) S. Achyutha Rao, T.-S. Chou, I. Schipor and P. Knochel,
Tetrahedron, 1992, 48, 2025.
3 J. V. Comasseto, P. H. Menzes, H. A. Stefani, G. Zeni and A. L.
Braga, Tetrahedron, 1996, 52, 9687.
4 (a) D. L. J. Clive, Tetrahedron, 1978, 34, 1049; (b) H. J. Reich,
Acc. Chem. Res., 1979, 12, 22.
5 (a) H. J. Reich, J. M. Renga and I. L. Reich, J. Am. Chem. Soc.,
1975, 97, 5434; (b) I. Ryu, S. Murai, I. Niwa and N. Sonoda,
Synthesis, 1977, 874; (c) R. Baudat and M. Petrzilka, Helv.
Chim. Acta, 1979, 62, 1406; (d) N. Miyoshi, T. Yamamoto,
N. Kambe, S. Murai and N. Sonoda, Tetrahedron Lett., 1982,
23, 4813; (e) I. Matsuda and S. Sato, J. Organomet. Chem.,
1986, 314, 47.
6 (a) I. Kuwajima and M. Shimizu, Tetrahedron Lett., 1978, 1277;
(b) M. Shimizu, R. Takeda and I. Kuwajima, ibid., 1979, 419;
(c) M. Shimizu and I. Kuwajima, Bull. Chem. Soc. Jpn., 1981,
54, 3100.
Conversion of Seleno-substituted Organozinc Chlorides 2 into the
Corresponding Copper Reagents 3.ÐA dry ¯ask equipped with a
magnetic stirring bar under nitrogen was charged with lithium
chloride (0.085 g, 2.0 mmol; previously dried under vacuum at
130 8C for 2 h) and copper cyanide (0.087 g, 1.0 mmol) and ¯ushed
three times with nitrogen. The mixture was dissolved in dry THF
(2 ml). The resulting yellowish solution was cooled to 78 8C and
the zinc reagent 2, prepared as described above, was slowly added
via cannula. The reaction mixture was allowed to warm to 0 8C for
5 min and then cooled again to 78 8C. Acyl chloride (0.6 mmol)
was added and the mixture allowed to warm to 10 8C and main-
tained at this temperature for 4 h in the case of the aryl-substituted
acyl chlorides, for 6 h in the case of alkyl-substituted acyl chlorides.
Then the mixture was treated with a saturated solution of NH4Cl
(10 ml) and NH4OH (10 ml), extracted with diethyl ether (20 ml Â2)
and the organic layer washed with brine and dried with MgSO4.
The solvents were evaporated and the product separated from the
residue through preparative TLC (silica gel) with cyclohexane±ethyl
acetate (20:1) as eluent. Yields are indicated in Table 1. For physi-
cal and spectral data see Table 2.
7 H. J. Reich, J. Org. Chem., 1974, 39, 428.
8 (a) K. B. Sharpless, R. F. Lauer and A. Y. Teranish, J. Am.
Chem. Soc., 1973, 95, 6137; (b) T. K. Ying, W. L. Bao and
Y. M. Zhang, Synth. Commun., 1996, 26, 1517.
9 T. G. Back and R. G. Kerr, Tetrahedron, 1985, 41, 4759.
10 A. L. J. Beckwith and P. E. Pigou, Aust. J. Chem., 1986, 39, 77.
Projects 29493800, 29672008 were supported by the
National Natural Science Foundation of China and
Laboratory of Organometallic Chemistry, Shanghai Institute
of Organic Chemistry, Academia Sinica.