Stereoselective preparation of α-heteroatom substituted α, β- unsaturated ketones

Article abstract of DOI:10.1055/s-2000-6272

(E)-α-Selanylvinylzirconium and (E)-α-silylvinylzirconium complexes 2 were prepared conveniently via hydrozirconation of the alkynylselenides and the alkynylsilanes 1, respectively. Intermediates 2 were reacted with acyl chlorides 3 via Zr-Cu transmetallation with retention of the configuration to afford α-seleno or α-silyl α,β-unsaturated ketones 4 in good yield.

Full text of DOI:10.1055/s-2000-6272

SHORT PAPER
775
Stereoselective Preparation of a-Heteroatom Substituted a, b-Unsaturated
Ketones
Aiming Sun, Xian Huang*
Department of Chemistry, Zhejiang University, Xi-xi Campus, Hangzhou, 310028, P. R. China
Fax +86(571)8807077; E-mail: huangx @mail.hz.zj.cn
Received 13 December 1999; revised 21 February 2000
Table Synthesis of a-Seleno or a-Silyl a,b-Unsaturated Ketones
Abstract: (E)-a-Selanylvinylzirconium and (E)-a-silylvinylzirco-
nium complexes 2 were prepared conveniently via hydrozirconation
of the alkynylselenides and the alkynylsilanes 1, respectively. Inter-
mediates 2 were reacted with acyl chlorides 3 via Zr-Cu transmetal-
lation with retention of the configuration to afford a-seleno or a-
silyl a,b-unsaturated ketones 4 in good yield.
Entry
R
X
R’
Producta Yieldb
(%)
A
B
C
D
E
F
Pr
Pr
SeEt
SeEt
Ph
4a
4b
4c
4d
4e
4f
82
80
80
78
75
70
79
81
85
89
83
85
87
89
C5H11
Ph
Key words: alkynylselenides, alkynylsilanes, hydrozirconation,
Zr-Cu transmetallation, a-heteroatom substituted a,b-unsaturated
ketones, acylations
MeOCH2 SeEt
MeOCH2 SeEt
C5H11
Ph
EtSe
EtSe
Pr
SeEt
Many biologically active compounds occurring in nature
possess the structural skeleton of trisubstituted alk-
enes.1-3 Because both disubstituted alkenylselenides and
alkenylsilanes can be stereospecifically converted to
trisubstituted alkenes by reactions with nucleophiles4 or
electrophiles,5 the high-yield, stereoselective synthesis of
disubstituted alkenylselenides or alkenylsilanes is a high-
ly desirable goal. Hydrozirconation has emerged as a
unique hydrometallation with some attractive features,6
such as the high regioselectivity and stereoselectivity ob-
served with alkynes.7 However, to date, hydrozirconation
of alkynylselenides and alkynylsilanes has received less
attention.8,9 We now wish to report that a-seleno- or a-si-
lyl-substituted a,b-unsaturated ketones could be synthe-
sized by hydrozirconation of the alkynylselenides or the
alkynylsilanes, followed by treatment with acyl halides
via Zr-Cu transmetallation.10
SeEt
Bu
G
H
I
SiMe3
SiMe3
SiMe3
C5H11
Ph
4g
4h
4i
Pr
Pr
4-ClC6H4
J
MeOCH2 SiMe3
MeOCH2 SiMe3
MeOCH2 SiMe3
MeOCH2 SiMe3
MeOCH2 SiMe3
2,3-(NO2)2C6H3 4j
K
L
M
N
Bu
4k
4l
Ph
4-ClC6H4
4m
3,4-(NO2)2C6H3 4n
a All the compounds were characterized using 1H NMR, IR, MS or
elemental analyses.
b Isolated yield based on the alkynylselenides or alkynylsilanes
used.
Alkynylselenides and alkynylsilanes 1 were prepared ac-
cording to the literature procedure.11,12 Hydrozirconation
of alkynylselenides and alkynylsilanes at room tempera-
ture in CH2Cl2 gave (E)-a-selanylvinylzirconiums and
(E)-a-silylvinylzirconiums 2, which were reacted with
acyl halides in the presence of 15mol% CuBr•SMe2 to af-
ford a-seleno or a-silyl a,b-unsaturated ketones 4. Trans-
metallation from Zr to Cu proceeded predominantly with
retention of configuration at carbon.13 The yields were
70-89% (Scheme 1).
Investigations of the crude products 4 by 1H NMR spec-
troscopy (300 MHz) showed isomeric purities of more
than 97%. One olefinic proton signal of 4 was character-
istically split into one triplet with coupling constant
J = 7.0 Hz, which indicated that the hydrozirconation of
the alkynylselenides or alkynylsilanes had taken place
with strong preference for the addition of the zirconium
atom at the carbon adjacent to the alkylseleno or alkylsilyl
group. The results of the reaction are summarized in the
Table.
We have also carried out the coupling reaction of the
compound 4l with aroyl halides in the presence of AlCl3
(1 equiv) at 0 °C in CH2Cl2 for an hour to give the unsat-
urated a,g-diketones 5 with high sterereoselectivity
(Scheme 2).
Scheme 1
Synthesis 2000, No. 6, 775–777 ISSN 0039-7881 © Thieme Stuttgart · New York

776
A. Sun, X. Huang
SHORT PAPER
4c
1H NMR (CDCl3): d = 7.92-7.74 (m, 2 H), 7.60-7.35 (m, 3 H), 6.34
(t, J = 7.1 Hz, 1 H, =CH), 4.15 (d, J = 7.1 Hz, 2 H, CH3OCH2), 3.34
(s, 3 H), 2.55 (q, J = 7.4 Hz, 2 H, SeCH2), 1.53 (t, J = 7.4 Hz, 3 H,
SeCH2CH3).
IR (film): n = 1698, 1650, 1202, 890 cm-1.
MS: m/z = 283 (M+).
Scheme 2
Anal. calcd for C13H16O2Se: C, 54.97; H, 5.68. Found: C, 55.01; H,
5.76.
In summary, our results showed that the hydrozircona-
tion-acylation sequence of the alkynylselenides and the
alkynylsilanes has the advantages of readily available
starting materials, straightforward and simple procedures,
mild reaction conditions and high yields. The investiga-
tion on the synthetic applications of these a-seleno and a-
silyl a,b-unsaturated ketones is in progress.
4d
1H NMR (CDCl3): d = 6.32 (t, J = 7.0 Hz, 1 H, =CH), 3.95 (d,
J = 7.0 Hz, 2 H, CH3OCH2), 3.35 (s, 3 H), 2.65 (t, J = 7.2 Hz, 2 H,
O=CCH2CH2), 2.57 (q, J = 7.4 Hz, 2 H, SeCH2), 1.52 (t, J = 7.4 Hz,
3 H, SeCH2CH3), 1.38-1.02 (m, 6 H), 0.84 (t, J = 5.4 Hz, 3 H,
CH2CH3).
IR (film): n = 1730, 1670, 1201, 905 cm-1.
MS: m/z = 277 (M+).
Anal. calcd for C12H22O2Se: C, 51.83; H, 7.97. Found: C, 51.49; H,
7.65.
1H NMR spectra were recorded on an AZ-300 MHz spectrometer
with TMS as an internal standard. Mass spectra were determined us-
ing a Finnigan 8230 mass spectrometer. IR spectra were obtained by
use of neat capillary cells on a Shimadzu IR-408 instrument. The re-
actions were carried out in pre-dried (150 °C, 4 h) glassware and
cooled under a stream of dry N2. All solvents were dried, deoxygen-
ated and freshly distilled before use
4e
1H NMR (CDCl3): d = 8.09-7.09 (m, 2 H), 7.55-7.45 (m, 3 H),
6.25 (s, 1 H), 2.65 (q, J = 7.4 Hz, 4 H, SeCH2), 1.40 (t, J = 7.4 Hz,
6 H, SeCH2CH3).
IR (film): n = 1735, 1683, 1210, 850 cm-1.
MS: m/z = 346 (M+).
a-Seleno- or a-Silyl-a,b-unsaturated Ketones 4a-n; General
Procedure
Anal. calcd for C13H16OSe2: C, 44.87; H, 4.64. Found: C, 44.98; H,
4.78.
To a suspension of hydridozirconocene chloride (310 mg, 1.2
mmol) in CH2Cl2 (2 mL) was added a solution of alkynylselenide or
alkynylsilane 1 (1.0 mmol) in CH2Cl2 at r.t. with stirring. After
about 30 min, the mixture turned to a clear green solution.
CuBr•SMe2 (25 mg) was then added, followed by the appropriate
acyl chloride (1.8 mmol). The mixture was stirred at 35 °C for about
20 min, quenched with sat. aq NaHCO3 (25 mL) and extracted with
wet Et2O (2 × 10 mL). The organic layer was dried (MgSO4), and
concentrated in vacuo. The oily residue was purified by flash col-
umn chromatography silica gel (EtOAc/hexanes, 1:8) to give 4a-n
as oils.
4f
1H NMR (CDCl3): d = 6.50 (s, 1 H), 2.68 (t, J = 7.1 Hz, 2 H,
O=CCH2CH2), 2.57 (q, J = 7.4 Hz, 4 H, SeCH2), 1.58 (t, J = 7.4 Hz,
6 H, SeCH2CH3), 1.45-1.23 (m, 4 H), 0.92 (t, J = 5.3 Hz, 3 H,
CH2CH3).
IR (film): n = 1722, 1683, 1318, 865 cm-1.
MS: m/z = 326 (M+).
Anal. calcd for C11H20OSe2: C, 40.29; H, 6.15. Found: C, 40.42; H,
6.32.
4a
1H NMR (CDCl3): d = 7.90-7.75 (m, 2 H), 7.45-7.20 (m, 3 H),
6.35 (t, J = 6.9 Hz, 1 H, =CH), 2.52 (q, J = 7.5 Hz, 2 H, SeCH2),
1.97-2.26 (m, 2 H), 1.49 (t, J = 7.5 Hz, 3 H, SeCH2CH3), 1.18-1.47
(m, 2 H), 0.75 (t, J = 5.3 Hz, 3 H, CH2CH3).
4g
1H NMR (CDCl3): d = 6.33 (t, J = 7.1 Hz, 1 H, =CH), 2.64 (t,
J = 7.1 Hz, 2 H, O=CCH2CH2), 2.26-1.97 (m, 2 H), 1.43-1.11 (m,
2 H), 1.03-0.83 (m, 12 H), 0.15 (s, 9 H).
IR (film): n = 1720, 1665, 1100, 892 cm-1.
MS: m/z = 281 (M+).
IR (film): n = 1710, 1665 cm-1.
MS: m/z = 239 (M+ - 1).
Anal. calcd for C14H18OSe: C, 59.60; H, 6.43. Found: C, 59.43; H,
6.22.
Anal. calcd for C14H28OSi: C, 70.00; H, 11.67. Found: C, 70.39; H,
11.42.
4b
1H NMR (CDCl3): d = 6.32 (t, J = 7.0 Hz, 1 H, =CH), 2.64 (t,
J = 7.1 Hz, 2 H, O=CCH2CH2), 2.53 (q, J = 7.5 Hz, 2 H, SeCH2),
2.26-1.98 (m, 2 H), 1.48 (t, J = 7.5 Hz, 3 H, SeCH2CH3), 1.43-1.10
(m, 2 H), 1.02-0.84 (m, 12 H).
4h
1H NMR (CDCl3): d = 8.15-7.21 (m, 5 H), 6.34 (t, J = 7.0 Hz, 1
H, =CH), 2.24-1.98 (m, 2 H), 1.42-1.30 (m, 2 H), 0.85 (t, J = 5.3
Hz, 3 H, CH2CH3), 0.15 (s, 9 H).
IR (film): n = 1725, 1645, 1102, 910 cm-1.
MS: m/z = 275 (M+).
IR (film): n = 1710, 1660, 700 cm-1.
MS: m/z = 245 (M+ - 1).
Anal. calcd for C13H24OSe: C, 56.54; H, 8.76. Found: C, 56.32; H,
8.45.
Anal. calcd for C15H22OSi: C, 73.17; H, 8.94. Found: C, 73.25; H,
8.88.
Synthesis 2000, No. 6, 775–777 ISSN 0039-7881 © Thieme Stuttgart · New York

SHORT PAPER
Stereoselective Preparation of a-Heteroatom Substituted a,b-Unsaturated Ketones
777
4i
mL) was added a solution of the appropriate aroyl halide (1.0 mmol)
in CH2Cl2 (2 mL)at r.t. and the mixture was stirred for 1 h. After the
usual workup (see above), the residue was purified by flash column
chromatography on silica gel (EtOAc/hexanes, 1:5) to give 5l and
5l’ as oils.
1H NMR (CDCl3): d = 7.93-7.86 (m, 2 H), 7.42-7.35 (m, 2 H),
6.33 (t, J = 7.2 Hz, 1 H, =CH), 2.25-1.97 (m, 2 H), 1.33 (m, 2 H),
0.89 (t, J = 5.3 Hz, 3 H, CH2CH3), 0.15 (s, 9 H).
IR (film): n = 1715, 1670, 750 cm-1.
MS: m/z = 280 (M+ - 1).
5l
1H NMR (CDCl3): d = 8.12-7.23 (m, 11 H), 4.05 (d, J = 7.5 Hz, 2
Anal. calcd for C15H21ClOSi: C, 64.06; H, 7.47. Found: C, 64.32; H,
7.27.
H), 3.25 (s, 3 H).
IR (film: n = 1718, 1670, 720 cm-1.
4j
MS: m/z = 280 (M-1).
1H NMR (CDCl3): d = 9.10 (s, 3 H), 6.29 (t, J = 7.2 Hz, 1 H, =CH),
3.85 (d, J = 7.2 Hz, 2 H, CH3OCH2), 3.28 (s, 3 H), 0.16 (s, 9 H).
Anal. calcd for C18H16O3: C, 77.14; H, 5.71. Found: C, 77.33; H,
5.65.
IR (film): n = 1720, 1665, 715 cm-1.
MS: m/z = 321 (M+ - 1).
5l’
1H NMR (CDCl3): d = 8.01-7.86 (m, 3 H), 7.42-7.35 (m, 2 H),
3.98 (d, J = 7.6 Hz, 2 H), 3.26 (s, 3 H).
Anal. calcd for C14H18N2O5Si: C, 52.34; H, 5.61. Found: C, 52.52;
H, 5.56.
IR (film): n = 1715, 1690, 750 cm-1.
MS: m/z = 315 (M+ - 1).
4k
1H NMR (CDCl3): d = 6.32 (t, J = 7.0 Hz, 1 H, =CH), 3.85 (d,
J = 7.0 Hz, 2 H, CH3OCH2), 3.28 (s, 3 H), 2.66 (t, J = 7.2 Hz, 2 H,
O=CCH2CH2), 1.37-1.03 (m, 4 H), 0.85 (t, J = 5.3 Hz, 3
H,CH2CH3), 0.16 (s, 9 H).
Anal. calcd for C18H15ClO3: C, 68.57; H, 4.76. Found: C, 68.78; H,
4.42.
IR (film): n = 1715, 1666 cm-1.
MS: m/z = 227 (M+ - 1).
Acknowledgement
Projects 29493800 and 29772007 were supported by the National
Natural Science Foundation of China. This work was also supported
by the Laboratory of Organometallic Chemistry, Shanghai Institu-
ted of Organic Chemistry, Academia Sinica.
Anal. calcd for C12H24O2Si: C, 63.16; H, 10.53. Found: C, 63.27; H,
10.46.
4l
1H NMR (CDCl3): d = 8.12-7.23 (m, 5 H), 6.32 (t, J = 7.0 Hz, 1
H, =CH), 4.05 (d, J = 7.0 Hz, 2 H, CH3OCH2), 3.25 (s, 3 H), 0.20
(s, 9 H).
References
(1) Marfat, P. R.; McGuirk, P.; Helquist, P. J. Org. Chem. 1979,
44, 3888.
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1979, 52, 1760.
(3) Masaki, Y.; Sakuma, K.; Kaji, K. J. Chem. Soc., Chem.
Commun. 1980, 434.
IR (film): n = 1713, 1670, 720 cm-1.
MS: m/z = 247 (M+ - 1).
Anal. calcd for C14H20O2Si: C, 67.74; H, 8.06. Found: C, 67.53; H,
8.18.
(4) Hercsi, L.; Heimaus, B.; Allard, C. Tetrahedron Lett. 1994,
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4m
1H NMR (CDCl3): d = 7.93-7.86 (m, 2 H), 7.42-7.35 (m, 2 H),
6.34 (t, J = 7.1 Hz, 1 H, =CH), 3.98 (d, J = 7.1 Hz, 2 H, CH3OCH2),
3.26 (s, 3 H), 0.15 (s, 9 H).
IR (film): n = 1715, 1680, 750 cm-1.
MS: m/z = 284 (M+ - 1).
Anal. calcd for C14H21SiClO2: C, 58.95; H, 7.37. Found: C, 58.76;
H, 7.48.
4n
1H NMR (CDCl3): d = 9.10 (s, 3 H), 6.32 (t, J = 7.2 Hz, 1 H, =CH),
3.95 (d, J = 7.2 Hz, 2H, CH3OCH2), 3.27 (s, 3 H), 0.17 (s, 9 H).
(13) (a) Lipshutz, B. H.; Keil, R. J. Am. Chem. Soc. 1992, 114,
7919.
IR (film): n = 1720, 1685, 720 cm-1.
MS: m/z = 337 (M+ - 1).
(b) Carr, D. B.; Schwartz, J. J. Am. Chem. Soc. 1979, 101,
3521.
Anal. calcd for C14H18N2O6Si: C, 49.70; H, 5.33. Found: C, 49.86;
H, 5.29.
Article Identifier:
1437-210X,E;2000,0,06,0775,0777,ftx,en;F07799SS.pdf
a,g-Diketones 5; General Procedure
To a stirred suspension of AlCl3 (133 mg, 1.0 mmol) and freshly
prepared a-silyl a,b-unsaturated ketone 4l (1.0 mmol) in CH2Cl2 (2
Synthesis 2000, No. 6, 775–777 ISSN 0039-7881 © Thieme Stuttgart · New York