Stereoselective synthesis of (Z)-α,β-unsaturated ketones via hydromagnesiation of alkynylsilanes

Article abstract of DOI:10.1081/SCC-120018925

Hydromagnesiation of alkynylsilanes 1 gives (Z)-α-silylvinyl Grignard reagents 2, which are treated with alkyl iodides in the presence of CuI to give (Z)-1,2-disubstituted vinylsilanes 3 in high yields. Intermediates 3 can undergo the Friedel-Crafts acyla

Full text of DOI:10.1081/SCC-120018925

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Stereoselective Synthesis of (Z)-α,β-Unsaturated
Ketones via Hydromagnesiation of Alkynylsilanes
Hong Zhao & Ming-Zhong Cai
To cite this article: Hong Zhao & Ming-Zhong Cai (2003) Stereoselective Synthesis of (Z)-α,β-
Unsaturated Ketones via Hydromagnesiation of Alkynylsilanes, Synthetic Communications, 33:10,
1643-1650, DOI: 10.1081/SCC-120018925
To link to this article: http://dx.doi.org/10.1081/SCC-120018925
Published online: 17 Aug 2006.
Submit your article to this journal
Article views: 43
View related articles
Citing articles: 4 View citing articles
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=lsyc20
Download by: [BYU Brigham Young University]
Date: 22 February 2017, At: 10:44

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 10, pp. 1643–1650, 2003
Stereoselective Synthesis of (Z )-a,b-Unsaturated
Ketones via Hydromagnesiation of Alkynylsilanes
*
Hong Zhao and Ming-Zhong Cai
Department of Chemistry, Jiangxi Normal University,
Nanchang, P.R. China
ABSTRACT
Hydromagnesiation of alkynylsilanes
1 gives (Z )-a-silylvinyl
Grignard reagents 2, which are treated with alkyl iodides in the pres-
ence of CuI to give (Z )-1,2-disubstituted vinylsilanes 3 in high yields.
Intermediates 3 can undergo the Friedel–Crafts acylation reactions
with acyl chlorides to afford (Z )-a,b-unsaturated ketones in good
yields with high stereoselectivity.
a,b-Unsaturated ketones are important synthetic intermediates
because of their versatile reactivities and many synthetic applications of
them have been reported in the literature.[1] The great synthetic value of
these a,b-unsaturated ketones derives from the fact that the positions a, b
and g to the carbonyl groups can be activated and functionalized by
*Correspondence: Ming-Zhong Cai, Department of Chemistry, Jiangxi Normal
University, Nanchang 330027, P.R. China; E-mail: caimz@fm365.com.
1643
DOI: 10.1081/SCC-120018925
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1644
Zhao and Cai
various means. A number of methods can be used for the stereoselective
synthesis of (E )-a,b-unsaturated ketones, such as the condensation
reactions of dibutyl telluride with a-halogenated ketones and aromatic
aldehydes,[2] by the palladium catalyzed stepwise cross-coupling reactions
of (E )-(2-bromoethenyl) diisopropoxyborane with a-alkoxyalkenylzinc
chlorides and organic halides,[3] by the conjugate addition of sulfonyl
carbanions to nitroalkenes followed by ozonolysis and then the elimina-
tion of sulfinic acid,[4] by CeCl3 mediated addition of Grignard reagents
to b-enamino ketones,[5] and Nickel(0)-catalyzed hydroacylation of
alkynes with aldehydes.[6] However, only a few methods for the synthesis
of (Z )-a,b-unsaturated ketones are available. The palladium catalyzed
coupling reactions of alkenyl copper reagents with acid chlorides afforded
(Z )-a,b-unsaturated ketones.[7]
The phase transfer catalyzed hydroacylation of allenes with carbon
monoxide, decacarbonyldimanganese and methyl iodide gave (Z )-a,b-
unsaturated ketones in a stereospecific process.[8]
Hydromagnesiation has emerged as a unique hydrometallation
with some attractive features, such as the high regioselectivity and stereo-
selectivity observed with alkynylsilanes.[9,10] We now wish to report that
(Z )-a,b-unsaturated ketones could be conveniently synthesized by
hydromagnesiation of alkynylsilanes, followed by treatment with alkyl
iodide and then the Friedel–Crafts acylation (Sch. 1).
Alkynylsilanes were easily prepared according to the literature
ꢀ
procedure.[11] Hydromagnesiation of alkynylsilanes 1 at25 C in ether
for 6 h afforded (Z )-a-silylvinyl Grignard reagents 2, which were treated
with methyl iodide at room temperature to give (Z )-1,2-disubstituted
vinylsilanes 3 in high yields. The intermediates 2 was found to present
low reactivity with alkyl halides other than methyl iodide, however, it was
readily alkylated by alkyl iodides in the presence of 10 mol% CuI to
Scheme 1.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Stereoselective Synthesis of (Z)-a,b-Unsaturated Ketones
Table 1. Synthesis of (Z )-1,2-disubstituted vinylsilanes 3.
1645
Entry
R
R1
Catalyst
Producta
Yieldb (%)
1
2
3
4
5
6
n-C4H9
n-C4H9
i-C5H11
i-C5H11
n-C6H13
n-C6H13
CH3
n-C4H9
CH3
3a
3b
3c
3d
3e
3f
91
86
88
87
89
85
CuI
CuI
CuI
n-C4H9
CH3
n-C4H9
aAll compounds were characterized by 1H NMR, IR and elemental analyses.
bIsolated yield based on the alkynylsilane used.
afford (Z )-1,2-disubstituted vinylsilanes 3 in good yields. The typical
results are summarized in Table 1. Investigation of the crude products
3 by 1H NMR spectroscopy (300 MHz) showed isomeric purities of more
than 96%. The olefinic proton signal of 3 characteristically splits into a
triplet with coupling constant J ¼ 7.0 Hz, which indicated that the hydro-
magnesiation of alkynylsilanes had taken place with strong preference for
the addition of the magnesium atom at the carbon bearing the alkylsilyl
group. Since the configuration of the intermediates 2 was known[9] and
the coupling reaction of intermediates 2 with alkyl iodides occurs with
retentive configuration, the configuration of products 3 can be defined.
Vinylsilanes are important synthetic intermediates because of the
versatile reactivity of the silyl group and the carbon-carbon double
bond.[12] (Z )-1,2-Disubstituted vinylsilanes 3 are also effective precursors
for preparing (Z )-a,b-unsaturated ketones. They can easily undergo the
Friedel–Crafts acylation with acyl chlorides with retention of configura-
tion providing a convenient route to (Z )-a,b-unsaturated ketones. Thus,
the Friedel–Crafts acylation of compounds 3 with acyl chlorides at 0ꢀC in
methylene chloride for 1 h afforded (Z )-a,b-unsaturated ketones 4 in
good yields with high stereoselectivity. Both aliphatic and aromatic
acid chlorides could be used as the acylating agents. The experimental
results are summarized in Table 2. While the geometries of products 4
were not rigorously established, a reasonable assumption is made that the
Friedel–Crafts acylation reaction proceeds stereospecifically with
complete retention of configuration.[13] The chemical shifts of the vinylic
protons for 4a–l are in the range of 5.29–5.60 ppm, which is consistent
with the (Z )-configuration of products 4.[14]
In summary, compared to other methods that have been reported,[7,8]
the present method for the stereoselective synthesis of (Z )-a,b-
unsaturated ketones has the advantages of readily available starting

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1646
Zhao and Cai
Table 2. Synthesis of (Z )-a,b-unsaturated ketones 4.
Entry
R
R1
R2
Producta
Yieldb (%)
1
2
n-C4H9
n-C4H9
n-C4H9
n-C4H9
i-C5H11
i-C5H11
i-C5H11
i-C5H11
n-C6H13
n-C6H13
n-C6H13
n-C6H13
CH3
CH3
CH3
Ph
4a
4b
4c
4d
4e
4f
74
81
68
80
74
76
83
81
75
69
71
77
3
n-C4H9
n-C4H9
CH3
CH3
4-ClC6H4
CH3
Ph
4
5
6
CH3
7
n-C4H9
n-C4H9
CH3
CH3
Ph
4g
4h
4i
8
9
CH3
4-ClC6H4
CH3
Ph
10
11
12
CH3
n-C4H9
n-C4H9
4j
4k
4l
1
aAll compounds were characterized using H NMR, IR, and elemental analyses.
bIsolated yield based on the (Z )-1,2-disubstituted vinylsilane used.
materials, straightforward, simple procedures, mild reaction conditions,
and high yields.
EXPERIMENTAL
1H NMR spectra were recorded on an AZ-300 MHz spectrometer
with TMS as an internal standard in CDCl3 as solvent. IR spectra
were obtained by use of neat capillary cells on a Shimadzu IR-435
instrument. Microanalyses were performed on Vario EL and Perkin-
Elmer CHN 2400. All solvents were dried, deoxygenated and freshly
distilled before use.
General Procedure for the Synthesis of
(Z )-1,2-Disubstituted Vinylsilanes 3a, 3c, and 3e
To a solution of isobutylmagnesium bromide (4.5 mmol) in diethyl
ꢀ
ether (7 mL) was added Cp2TiCl2 (50 mg, 0.2 mmol) at0 C under Ar,
and the mixture was stirred for 30 min at that temperature. To this
solution was added alkynylsilane 1 (4.0 mmol), and the mixture was
stirred for 6 h at 25ꢀC. After removal of the ether under reduced pressure
(2 h, r.t./2 torr), the residue was dissolved in THF (6 mL) and treated with
methyl iodide (0.71 g, 5 mmol) at 0ꢀC for 10 min and then at room

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Stereoselective Synthesis of (Z)-a,b-Unsaturated Ketones
1647
temperature for 2 h. The resulting mixture was treated with sat. aq.
NH4Cl (25 mL) and extracted with Et2O (2 ꢁ 30 mL). The ethereal
solution was washed with water (3 ꢁ 30 mL) and dried (MgSO4).
Removal of solventunder reduced pressure gave an oil which was
purified by column chromatography on silica gel using light petroleum
as eluent.
3a: ꢀH 0.11 (s, 9H), 0.90 (t, 3H, J ¼ 5.4 Hz), 1.08–1.60 (m, 4H), 1.74
(s, 3H), 1.85–2.40 (m, 2H), 5.84 (t, 1H, J ¼ 7.0 Hz) ppm; ꢁmax 2958, 2860,
1620, 1466, 1249, 838 cmꢂ1; Anal. calcd. for C10H22Si: C, 70.59; H, 12.94.
Found: C, 70.36; H, 12.79.
3c: ꢀH 0.11 (s, 9H), 0.87 (d, 6H, J ¼ 6.4 Hz), 1.05–1.68 (m, 3H), 1.69
(s, 3H), 1.84–2.38 (m, 2H), 5.77 (t, 1H, J ¼ 7.0 Hz) ppm; ꢁmax 2955, 1618,
1467, 1384, 1366, 1248, 836 cmꢂ1; Anal. calcd. for C11H24Si: C, 71.74;
H, 13.04. Found: C, 71.50; H, 12.91.
3e: ꢀH 0.11 (s, 9H), 0.88 (t, 3H, J ¼ 5.4 Hz), 1.10–1.65 (m, 8H), 1.73
(s, 3H), 1.84–2.41 (m, 2H), 5.81 (t, 1H, J ¼ 7.0 Hz) ppm; ꢁmax 2926, 2856,
1607, 1458, 1248, 837 cmꢂ1; Anal. calcd. for C12H26Si: C, 72.73; H, 13.13.
Found: C, 72.51; H, 13.02.
General Procedure for the Synthesis of
(Z )-1,2-Disubstituted Vinylsilanes 3b, 3d, and 3f
To a solution of isobutylmagnesium bromide (4.5 mmol) in diethyl
ether (7 mL) was added Cp2TiCl2 (50 mg, 0.2 mmol) at0 ꢀC under Ar, and
the mixture was stirred for 30 min at that temperature. To this solution
was added alkynylsilane 1 (4.0 mmol), and the mixture was stirred for 6 h
ꢀ
at25 C. After removal of the ether under reduced pressure, the residue
was dissolved in THF (7 mL), cooled to ꢂ10ꢀC, and treated with butyl
iodide (0.828 g, 4.5 mmol) and CuI (76 mg, 0.4 mmol). The reaction mix-
ture was brought to room temperature gradually and stirred for 2 h. After
the usual workup (see above) the residue was chromatographed through
a silica gel column using light petroleum as eluent.
3b: ꢀH 0.11 (s, 9H), 0.66–1.08 (m, 6H), 1.10–1.62 (m, 8H), 1.78–2.40
(m, 4H), 5.83 (t, 1H, J ¼ 7.0 Hz) ppm; ꢁmax 2954, 2860, 1612, 1466, 1249,
848 cmꢂ1; Anal. calcd. for C13H28Si: C, 73.58; H, 13.21. Found: C, 73.40;
H, 13.13.
3d: ꢀH 0.12 (s, 9H), 0.78–1.05 (m, 9H), 1.08–1.64 (m, 7H), 1.74–2.38
(m, 4H), 5.83 (t, 1H, J ¼ 7.0 Hz) ppm; ꢁmax 2955, 2871, 1612, 1466, 1384,
1366, 1248, 835 cmꢂ1; Anal. calcd. for C14H30Si: C, 74.34; H, 13.27.
Found: C, 74.19; H, 13.06.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1648
Zhao and Cai
3f: ꢀH 0.11 (s, 9H), 0.68–1.03 (m, 6H), 1.04–1.72 (m, 12H), 1.74–2.40
(m, 4H), 5.82 (t, 1H, J ¼ 7.0 Hz) ppm; ꢁmax 2958, 2857, 1612, 1466, 1249,
838 cmꢂ1; Anal. calcd. for C15H32Si: C, 75.00; H, 13.33. Found: C, 75.11;
H, 13.24.
General Procedure for the Synthesis of
(Z )-a,b-Unsaturated Ketones 4a–l
To a stirred suspension of AlCl3 (146 mg, 1.1 mmol) and (Z )-1,2-
disubstituted vinylsilane 3 (1.0 mmol) in CH2Cl2 (2 mL) was added a
solution of the appropriate acyl chloride (1.0 mmol) in CH2Cl2 (2 mL)
at0 ꢀC and the mixture was stirred for1 h. The reaction mixture was
treated with sat. aq. NaHCO3 (10 mL) and extracted with Et2O
(2 ꢁ 20 mL). The organic layer was washed with water (3 ꢁ 20 mL),
dried (MgSO4) and concentrated in vacuo. The oily residue was purified
by flash column chromatography on silica gel (EtOAc/light petroleum, 1:8)
to give 4a–l as oils.
4a: ꢀH 0.89 (t, 3H, J ¼ 5.4 Hz), 1.08–1.80 (m, 4H), 1.90 (s, 3H),
2.04–2.50 (m, 5H), 5.55 (m, 1H) ppm; ꢁmax 2958, 2870, 1690, 1641,
1467 cmꢂ1; Anal. calcd. for C9H16O: C, 77.14; H, 11.43. Found: C,
76.89; H, 11.21.
4b: ꢀH 0.91 (t, 3H, J ¼ 5.4 Hz), 1.05–1.75 (m, 4H), 1.91 (s, 3H),
2.05–2.41 (m, 2H), 5.50 (m, 1H), 7.18–7.63 (m, 3H), 7.65–7.97 (m,
2H) ppm; ꢁmax 2957, 2872, 1665, 1598, 1448, 1337 cmꢂ1; Anal. calcd.
for C14H18O: C, 83.17; H, 8.91. Found: C, 83.26; H, 8.83.
4c: ꢀH 0.69–1.10 (m, 6H), 1.12–1.78 (m, 8H), 1.91–2.40 (m, 7H), 5.25
(m, 1H) ppm; ꢁmax 2958, 2872, 1670, 1637, 1458 cmꢂ1; Anal. calcd. for
C12H22O: C, 79.12; H, 12.09. Found: C, 79.33; H, 12.14.
4d: ꢀH 0.67–1.11 (m, 6H), 1.12–1.83 (m, 8H), 1.98–2.41 (m, 4H), 5.42
(m, 1H), 7.39 (d, 2H, J ¼ 9.0 Hz), 7.86 (d, 2H, J ¼ 9.0 Hz) ppm; ꢁmax 2957,
2865, 1666, 1595, 1490, 1445 cmꢂ1; Anal. calcd. for C17H23OCl: C, 73.25;
H, 8.26. Found: C, 73.40; H, 8.38.
4e: ꢀH 0.87 (d, 6H, J ¼ 6.4 Hz), 1.09–1.78 (m, 3H), 1.92 (s, 3H),
2.01–2.41 (m, 5H), 5.50 (m, 1H) ppm; ꢁmax 2960, 2871, 1690, 1640,
1467, 1384, 1366 cmꢂ1; Anal. calcd. for C10H18O: C, 77.92; H, 11.69.
Found: C, 77.65; H, 11.47.
4f: ꢀH 0.91 (d, 6H, J ¼ 6.4 Hz), 1.08–1.81 (m, 3H), 1.91 (s, 3H),
2.04–2.42 (m, 2H), 5.45 (m, 1H), 7.16–7.61 (m, 3H), 7.65–7.98
;
(m, 2H) ppm; ꢁmax 2955, 2870, 1664, 1598, 1448, 1384, 1366 cmꢂ1
Anal. calcd. for C15H20O: C, 83.33; H, 9.26. Found: C, 83.05; H, 9.11.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Stereoselective Synthesis of (Z)-a,b-Unsaturated Ketones
1649
4g: ꢀH 0.70–1.10 (m, 9H), 1.11–1.80 (m, 7H), 1.95–2.41 (m, 7H), 5.29
(m, 1H) ppm; ꢁmax 2957, 2871, 1670, 1637, 1466, 1384, 1366 cmꢂ1; Anal.
calcd. for C13H24O: C, 79.59; H, 12.24. Found: C, 79.35; H, 12.07.
4h: ꢀH 0.67–1.10 (m, 9H), 1.11–1.78 (m, 7H), 1.85–2.40 (m, 4H), 5.38
(m, 1H), 7.10–7.57 (m, 3H), 7.68–7.99 (m, 2H) ppm; ꢁmax 2956, 2871,
1683, 1597, 1448, 1384, 1366 cmꢂ1; Anal. calcd. for C18H26O: C, 83.72;
H, 10.08. Found: C, 83.50; H, 9.85.
4i: ꢀH 0.90 (t, 3H, J ¼ 5.4 Hz), 1.09–1.80 (m, 8H), 1.92 (s, 3H),
2.00–2.41 (m, 5H), 5.60 (m, 1H) ppm; ꢁmax 2931, 2858, 1681, 1629,
1458 cmꢂ1; Anal. calcd. for C11H20O: C, 78.57; H, 11.90. Found: C,
78.31; H, 11.71.
4j: ꢀH 0.90 (t, 3H, J ¼ 5.4 Hz), 1.10–1.79 (m, 8H), 1.91 (s, 3H),
1.97–2.39 (m, 2H), 5.50 (m, 1H), 7.35 (d, 2H, J ¼ 9.0 Hz), 7.84 (d, 2H,
J ¼ 9.0 Hz) ppm; ꢁmax 2958, 2865, 1662, 1623, 1595, 1445 cmꢂ1; Anal.
calcd. for C16H21OCl: C, 72.59; H, 7.94. Found: C, 72.31; H, 7.69.
4k: ꢀH 0.69–1.10 (m, 6H), 1.12–1.81 (m, 12H), 1.95–2.41 (m, 7H),
5.35 (m, 1H) ppm; ꢁmax 2958, 2872, 1683, 1632, 1466 cmꢂ1; Anal. calcd.
for C14H26O: C, 80.00; H, 12.38. Found: C, 79.75; H, 12.14.
4l: ꢀH 0.68–1.10 (m, 6H), 1.11–1.79 (m, 12H), 1.90–2.41 (m, 4H), 5.37
(m, 1H), 7.10–7.49 (m, 3H), 7.60–8.05 (m, 2H) ppm; ꢁmax 2957, 2859,
1683, 1622, 1598, 1448 cmꢂ1; Anal. calcd. for C19H28O: C, 83.82;
H, 10.29. Found: C, 83.58; H, 10.07.
ACKNOWLEDGMENTS
We thank the National Natural Science Foundation of China
(Project: 20062002) and the Natural Science Foundation of Jiangxi
Province for financial support.
REFERENCES
1. (a) House, H.O. Modern Synthetic Reactions, 2nd. Ed.; Benjamine,
W.A., Ed.; New York, 1972; (b) Volkmann, R.A.; Andrews, G.G.
J. Am. Chem. Soc. 1975, 97, 4777; (c) Stork, G.; Logusch, E.W.
Tetrahedron Lett. 1979, 3361; (d) House, H.O.; Umen, M.J. J. Org.
Chem. 1973, 38, 3893; (e) Brown, H.C. Synthesis 1984, 303.
2. Huang, X.; Xie, L.H.; Wu, H. J. Org. Chem. 1988, 53, 4862.
3. Ogima, M.; Hyuga, S.; Hara, S.; Suzuki, A. Chem. Lett. 1989, 1959.
4. Awen, B.Z.; Miyashita, M.; Shiratani, T.; Yoshikoshi, A.; Irie, H.
Chem. Lett. 1992, 767.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1650
Zhao and Cai
5. Bartoli, G.; Cimarelli, C.; Marcantoni, E.; Palmieri, G.; Petrini, M.
J. Chem. Soc., Chem. Commun. 1994, 715.
6. Tsuda, T.; Kiyoi, T.; Saegusa, T. J. Org. Chem. 1990, 55, 2554.
7. Jabri, N.; Alexakis, A.; Normant, J.F. Tetrahedron Lett. 1983,
24, 5081.
8. Satyanarayana, N.; Alper, H. J. Chem. Soc., Chem. Commun.
1991, 8.
9. Sato, F.; Watanabe, H.; Tanaka, Y.; Yamaji, T.; Sato, M.
Tetrahedron Lett. 1983, 24, 1041.
10. Sato, F. J. Organomet. Chem. 1985, 285, 53.
11. Eaborn, C.; Walton, D.R.M. J. Organomet. Chem. 1964, 2, 95.
12. Chan, T.H.; Fleming, I. Synthesis 1979, 761.
13. Fleming, I.; Pearce, A. J. Chem. Soc., Chem. Commun. 1975, 633.
14. Chan, T.H.; Lau, P.W.K.; Mychajlowskij, W. Tetrahedron Lett.
1977, 3317.
Received in Japan June 16, 2002