The reaction of the a-selenium stabilized copper reagents ArSeCH2Cu(CN)ZnCl

Article abstract of DOI:10.1039/a805991h

a-Arylseleno-substituted zinc and copper organometallics, in the presence of a Lewis acid, can react with aldehydes, ketones and enals with high chemoselectivity and_regioselectivity.

Full text of DOI:10.1039/a805991h

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26 J. CHEM. RESEARCH (S), 1999
J. Chem. Research (S),
1999, 26±27$
The Reaction of the a-Selenium Stabilized Copper
Reagents ArSeCH2Cu(CN)ZnCl with Aldehydes$
De-Hui Duan and Xian Huang*
Department of Chemistry, Hangzhou University, Hangzhou Zhejiang, 310028, P.R. China
ꢀ-Arylseleno-substituted zinc and copper organometallics, in the presence of a Lewis acid, can react with aldehydes,
ketones and enals with high chemoselectivity and regioselectivity.
The use of organozinc compounds in organic synthesis has
been paid increasing attention recently.1 Their excellent func-
tional group tolerance, high chemoselectivity and excellent
stereoselectivity in many reactions make organozincs ideal
organometallic intermediates for the construction of com-
plex polyfunctional molecules. We have already successfully
prepared zinc organometallics with an a-selenium functional
group and using CuCN±2LiCl have transmetallated them to
the corresponding copper reagents.2 Their reaction with acyl
chlorides has achieved satisfactory results. Herein, we report
the results of their reaction with aldehydes.
We found that copper reagent 2 (1 equiv.) reacts in the
presence of BF3±Et2O (2 equiv.) with various aldehydes (0.6
Scheme 2
We also ®nd that Lewis acids play an important role in
the reaction of ArSeCH2Cu(CN)ZnCl with a,b-unsaturated
aldehydes. Thus, acrolein in the presence of 2 equiv. of
equiv.) in THF at 0 8C (4±12 h) to furnish the a-selenium
functionalized secondary alcohols 3 in good yields (63±75%)
BF3±Et2O leads to a mixture of the 1,2-adduct (30%) and
the 1,4-adduct (35%), whereas in the presence of 2 equiv. of
(see Scheme 1 and Table 1). Aromatic aldehydes show the
Me3SiCl, only the 1,4-adduct is obtained in 79% yield (see
Scheme 3 and entries 5, 6 and 8 of Table 1). Zinc and cop-
Table 1). However, for aliphatic aldehydes a longer reaction
greatest reactivity (4 h at 0 8C) (see entries 1, 2 and 7 of
per organometallics therefore possess better regioselectivity
than the known organolithium reagents.4
time (12 h at 0 8C) is required (see entries 3 and 4 of
Table 1). Under our conditions, ketones do not react with
copper reagents 2. On treating a 1:1 mixture of benzal-
dehyde and acetophenone with PhSeCH2Cu(CN)ZnCl, we
obtained 1-phenyl-2-phenylselenoethanol in 70% yield
whereas acetophenone was recovered in 95% yield (see
Scheme 2).
Scheme 3
In conclusion, the easy preparation of a-seleno-
substituted organozinc chlorides 1, transmetallated to the
corresponding copper reagents ArSeCH2Cu(CN)ZnCl
2
Scheme 1
with their good reactivity, can react with aldehydes in good
yields whereas ketones remain almost intact in a 1:1 mixture
of the two electrophiles. Furthermore, in the presence
The reactivity of functionalized copper reagents
RCu(CN)ZnI depends strongly on the nature of additives.3
Table 1 Products obtained by the addition of copper reagents ArSeCH2Cu(CN)ZnCl to aldehydes in the presence of Lewis acid
Reaction
conditionsa
Yieldc
(%)
Entry
ArSeCH2Cu(CN)ZnCl
Aldehyde
Productb
1
2
3
4
5
PhSeCH2Cu(CN)ZnCl 2a
PhCHO
A
A
B
B
B
PhSeCH2CH(OH)Ph 3a
72
75
65
63
30
35
79
74
75
2a
2a
2a
2a
p-NO2C6H4CHO
BuCHO
HexCHO
PhSeCH2CH(OH)C6H4NO2-p 3b
PhSeCH2CH(OH)Bu 3c
PhSeCH2CH(OH)Hex 3d
.
CH2 CHCHO
.
PhSeCH2CH(OH)CH CH2 3e
‡ PhSeCH2CH2CH2CHO 4a
PhSeCH2CH2CH2CHO 4a
p-TolylSeCH2CH(OH)Ph 3f
p-TolylSeCH2CH2CH2CHO 4b
.
CH2 CHCHO
PhCHO
.
CH2 CHCHO
6
7
8
2a
p-TolylSeCH2Cu(CN)ZnCl 2b
2b
C
A
C
aReaction conditions A: in the presence of 2 equiv. of BF3±Et2O, 0 8C, 4 h; B: in the presence of 2 equiv. of BF3±Et2O, 0 8C, 12 h;
C: in the presence of 2 equiv. of Me3SiCl, 25 8C, 12 h. bAll products are oils at room temperature. cYields of pure compounds.
of Me3SiCl, the reaction with enals takes place only in
the form of a 1,4-addition. Their reaction towards other
carbon electrophiles is currently being investigated in our
laboratory.
*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), 1999, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).

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J. CHEM. RESEARCH (S), 1999 27
C, 51.83; H, 3.99; N, 4.04. C14H13NO3Se requires C, 52.18; H, 4.07;
N, 4.34%.).
Experimental
1H NMR spectra were recorded in CCl4 or CDCl3 on a JEOL
PMX 60si spectrometer using tetramethylsilane as internal standard.
Chemical shifts are reported as d in ppm. J are reported in Hz. IR
spectra were obtained on a PE683 spectrometer. Mass spectra (MS)
1
1-Phenylselenohexan-2-ol7 3c.Ðꢂ/cm 3450, 3085, 2980, 2865,
1590, 1440, 1025, 900, 790, 737, 690. ꢁH (CCl4): 0.88±1.53 (m, 9H,
Bun ), 2.45 (br s, 1H, OH), 2.92±3.18 (m, 2H, CH2Se), 3.63±3.71 (m,
1H, CHO), 7.23±7.60 (m, 5H, ArH).
were recorded on
a HP5989A mass spectrometer. Elemental
1
1-Phenylselenooctan-2-ol8 3d.Ðꢂ/cm
3350, 3090, 3075, 2980,
analyses were performed on a Carlo-Erba 1106. Tetrahydrofuran
(THF) was distilled from sodium±benzophenone, immediately
before use. Chloromethyl selenides were prepared according to
the literature.5 Aldehydes were redistilled under the protection of
N2 prior to use. The remaining chemicals were obtained from
commercial sources. All reactions were performed under a nitrogen
atmosphere.
2942, 2870, 1590, 1448, 1025, 788, 737, 690. ꢁH (CDCl3): 0.83±1.60
(m, 13H, n-C6H13), 2.92±3.10 (m, 2H, CH2Se), 3.30 (br s, 1H, OH),
3.37±3.80 (m, 1H, CHO), 7.16±7.73 (m, 5H, ArH).
1
4-Phenylselenobut-1-en-3-ol9 3e.Ðꢂ/cm 3400, 3095, 3080, 2970,
2865, 1645, 1590, 1440, 1025, 740, 690. ꢁH (CDCl3): 2.68 (br s, 1H,
OH), 2.90±3.06 (m, 2H, CH2-Se), 4.04±4.16 (m, 1H, CH-O), 5.02
(dd, 1H, J 10, 2), 5.15 (dd, 1H, J 16, 2), 5.80 (ddd, 1H, J 16, 10, 6),
General Procedure for the Preparation of Phenylselenomethylzinc
Chlorides 1.ÐA dry three-necked ¯ask equipped with a magnetic
stirring bar and a thermometer under nitrogen was charged with
zinc dust (0.29 g, 4.5 mmol) and ¯ushed three times with nitrogen.
A solution of 1,2-dibromoethane (0.03 g, 0.15 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
(0.03 g, 0.15 mmol) was added. After 10 min of stirring at room
temperature, a solution of chloromethyl phenyl selenide (0.31 g,
1.5 mmol) in THF (2 ml) was added dropwise over 10 min. The
reaction mixture was stirred for 9 h at 25 8C. The reaction process
was monitored and the yield was estimated by 1H NMR analysis
of hydrolysed reaction aliquots. After 9 h, the peak at ꢁ 4.92
(s, PhSeCH2Cl) disappeared and the peak at ꢁ 2.27 (s, PhSeCH3)
reached a maximum, approximately 75% yield. The excess zinc was
allowed to settle and the resulting clear solution was ready to use
for further transformation.
7.12±7.60 (m, 5H, ArH).
1
4-Phenylselenobutanal10 4a.Ðꢂ/cm
3040, 2940, 2830, 2740,
1735, 1590, 1485, 1440, 1390, 1070, 1020, 730, 685. ꢁH (CDCl3):
.
2.00 (q, 2H, J 7.1, CCH2C), 2.52 (t, 2H, J 7.1, CCH2C O), 2.86
(t, 2H, J 7.1, SeCH2C), 7.04±7.56 (m, 5H, ArH), 9.74 (s, 1H,
CHO).
1
1-Phenyl-2-p-tolyselenoethan-1-ol 3f.Ðꢂ/cm
3440, 3080, 3050,
2950, 2870, 1590, 1490, 1460, 1450, 1200, 1060, 790. ꢁH (CCl4): 2.30
(s, 3H, CH3Ar), 2.73±2.92 (m, 1H, OH), 3.06±3.17 (m, 2H, CH2Se),
4.43±4.66 (m, 1H, CHO), 6.96 (d, 2H), 7.23±7.59 (m, 5H),
7.68±7.85 (m, 2H), MS: m/z 292 and 290 (M ),% 186, 171, 169, 107,
91 (Found: C, 61.49; H, 5.85. C15H16OSe requires C, 61.85;
H, 5.54%).
4-p-Tolylselenobutanal 4b.Ðꢂ/cm 3095, 3085, 2940, 2830, 2740,
1735, 1590, 1485, 1440, 1390, 1070, 1020, 790. ꢁH (CCl4): 2.03
(q, 2H, J 7.1, CCH2C), 2.30 (s, 3H, CH3Ar), 2.50 (t, 2H, J 7.1,
‡
1
.
CH2C O), 2.97 (t, 2H, J 7.1, CCH2Se), 6.97 (d, 2H, J 8), 7.40
‡
(d, 2H, J 8), 9.69 (s, 1H, CHO). MS: m/z 242 and 240 (M ),% 213,
198, 186, 185, 171, 44, 29. (Found C, 55.12; H, 5.80. C11H14OSe
requires C, 54.77; H, 5.85%).
Conversion of Seleno-substituted Organozinc Chloride 1 to the
Corresponding Copper Reagents 2 and Reaction with Aldehydes.ÐA
dry ¯ask equipped with a magnetic stirring bar was charged under
nitrogen with lithium chloride (0.13 g, 3.0 mmol; previously dried
under vacuum at 130 8C for 2 h) and copper cyanide (0.13 g,
1.5 mmol) and was ¯ushed three times with nitrogen. The mixture
was dissolved in 2 ml of dry THF. The resulting yellowish solution
was cooled to 78 8C and the zinc reagent 1, prepared as described
above, was slowly added via a cannula. The reaction mixture was
allowed to warm to 0 8C for 5 min and then cooled again to
78 8C. After the aldehyde (0.67 mmol) and the appropriate Lewis
acid (2.2 mmol) had been added, the mixture was allowed to warm
to 0 8C (or 25 8C) and maintained at this temperature for 4 h in
the case of the aromatic aldehydes, and for 12 h for the aliphatic
aldehydes. Then the mixture was treated with a saturated solution
of NH4Cl (10 ml) and NH4OH (10 ml), extracted with diethyl ether
(2Â 20 ml) and the organic layer was washed with brine and dried
with MgSO4. The solvents were evaporated and the product was
separated from the residue through preparative TLC (silica gel)
with cyclohexane±ethyl ether (4:1) as eluent. Yields are shown in
Table 1.
Projects 29493800 and 29672008 were supported by
the National Natural Science Foundation of China and
Laboratory of Organometallic Chemistry, Shanghai Institute
of Organic Chemistry, Academia Sinica.
Received, 1st December 1998; Accepted, 1st December 1998
Paper E/8/05991H
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1
1-Phenyl-2-phenylselenoethan-1-ol6 3a.Ðꢂ/cm 3440, 3080, 2950,
1590, 1490, 1460, 1200, 1050, 730, 700. ꢁH (CCl4): 2.65±2.85 (m,
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7.00±7.50 (m, 10H, ArH).
1
1-p-Nitrophenyl-2-phenylselenoethan-1-ol 3b.Ðꢂ/cm 3440, 3090,
2940, 1610, 1590, 1520, 1480, 1440, 1350, 1190, 1060, 900, 730, 680.
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CHO), 7.13±7.60 (m, 7H, ArH), 8.13 (d, 2H, ArH). MS:
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78Se(23.52), 80Se(49.82), 82Se(9.19%), but only the peaks due to the
isotopes 80Se and 78Se are reported here.
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