A novel synthesis of β-aryl-α,β-unsaturated amides

Article abstract of DOI:10.1081/SCC-100104004

A new simple method for the efficient synthesis of β-aryl-α,β-unsaturated amides has been developed. The route involves nickel-catalyzed oxidation of benzyl alcohol, followed by Aldol-type condensation with N,N-dimethylacetamide in one step.

Full text of DOI:10.1081/SCC-100104004

This article was downloaded by: [University of Western Ontario]
On: 16 November 2014, At: 17:04
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number:
1072954 Registered office: Mortimer House, 37-41 Mortimer Street,
London W1T 3JH, UK
Synthetic Communications:
An International Journal
for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
A NOVEL SYNTHESIS OF β-
ARYL-α,β-UNSATURATED
AMIDES
Hong-Jun Ren a & Yan-Guang Wang b
a Department of Chemistry , Zhejiang University ,
Hangzhou, 310027, P.R. China
b Department of Chemistry , Zhejiang University ,
Hangzhou, 310027, P.R. China
Published online: 09 Nov 2006.
To cite this article: Hong-Jun Ren & Yan-Guang Wang (2001) A NOVEL SYNTHESIS
OF β-ARYL-α,β-UNSATURATED AMIDES, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 31:8, 1201-1204,
DOI: 10.1081/SCC-100104004
To link to this article: http://dx.doi.org/10.1081/SCC-100104004
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all
the information (the “Content”) contained in the publications on our
platform. However, Taylor & Francis, our agents, and our licensors
make no representations or warranties whatsoever as to the accuracy,
completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of
the authors, and are not the views of or endorsed by Taylor & Francis.
The accuracy of the Content should not be relied upon and should be

independently verified with primary sources of information. Taylor and
Francis shall not be liable for any losses, actions, claims, proceedings,
demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in
relation to or arising out of the use of the Content.
This article may be used for research, teaching, and private study
purposes. Any substantial or systematic reproduction, redistribution,
reselling, loan, sub-licensing, systematic supply, or distribution in any form
to anyone is expressly forbidden. Terms & Conditions of access and use
can be found at http://www.tandfonline.com/page/terms-and-conditions

SYNTHETIC COMMUNICATIONS, 31(8), 1201–1204 (2001)
A NOVEL SYNTHESIS OF
b-ARYL-a,b-UNSATURATED AMIDES
Hong-Jun Ren and Yan-Guang Wang*
Department of Chemistry, Zhejiang University,
Hangzhou 310027, P.R. China
ABSTRACT
A new simple method for the efficient synthesis of ꢀ-
aryl-ꢁ,ꢀ-unsaturated amides has been developed.The route
involves nickel-catalyzed oxidation of benzyl alcohol, fol-
lowed by Aldol-type condensation with N,N-dimethylaceta-
mide in one step.
ꢀ-Aryl-ꢁ,ꢀ-unsaturated amides are common in synthetic chemistry.
New, simple, and efficient methods for their synthesis would, therefore, be
valuable.Benzyl alcohols would be suitable precursors to ꢀ-aryl-ꢁ,ꢀ-unsatu-
rated amides if mild and simple methods for oxidation of alcohol and the
following condensation in one step could be found.The palladium-catalyzed
oxidation of primary and secondary alcohols to aldehydes and ketones,
respectively, has been reported in recent years.1–9 Many types of reoxidants
such as metal salts, O2,1–3 peroxides,4 and organic halides5–7 have been used
to take the reduced palladium back to the active state in this oxidation.We
recently investigated the scope of this reaction using nickel complexes as
catalysts because (1) nickel alkoxide complexes are known;10,11 (2) first-row
transition metals are often more reactive than second-row metals;12 (3)
nickel complexes are known to catalyze cross-coupling processes through
* Corresponding author.
1201
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

1202
REN AND WANG
mechanisms not likely to occur with palladium complexes;13–15 and (4)
nickel is less expensive than palladium.
We now report a new simple method for the efficient synthesis of
ꢀ-aryl-ꢁ,ꢀ-unsaturated amides via a nickel-catalyzed oxidation of benzyl
alcohol, followed by Aldol-type condensation with N,N-dimethylacetamide
in one step.The major products formed by this method are E-isomers.
RESULTS AND DISCUSSION
The overall reaction is shown in Scheme 1.Benzyl alcohols 1 were
oxidized into aldehydes 4 using catalytic (1,10-phenanthroline)NiCl2
(5ꢀ8% mol).Chlorobenzene was used as reoxidant to take the reduced
nickel back to the active state in this oxidation (as shown in Scheme 2).
Base NaH was necessary to form nickel alkoxide complexes.Other bases,
such as K2CO3 and triethylamine, were used, but they did not work.An in
situ condensation of aldehydes 4 with N,N-dimethylacetamide in the pres-
ence of excess NaH resulted in (E)-ꢀ-aryl-ꢁ,ꢀ-unsaturated amides 3 as the
major products.16 As shown in Table 1, the isolated yields were 80 ꢀ 96%
GC/MS analysis of the crude reaction mixture showed that the amount of
Z-isomers was very little.17 This two-step reaction was carried out in one
step at room temperature.
Scheme 1. Synthesis of ꢀ-aryl-ꢁ,ꢀ-unsaturated amides.
Scheme 2. Mechanism of oxidation of benzyl alcohols.

b-ARYL-a,b-UNSATURATED AMIDES
Table 1. The Synthesis of ꢀ-Aryl-ꢁ,ꢀ-Unsaturated Amides
1203
Compd.R
% Isolated Yield
3a
3b
3c
3d
3e
H
80
96
85
90
94
CH3-m
CH3-p
F-p
N(CH3)2-m
Typical Procedure
To a solution of benzyl alcohol (2.0 mmol), chlorobenzene (2.0 mmol),
and sodium hydride (4.2 mmol) in N,N-dimethylacetamide (4 mL) was
added (1,10-phenanthroline)NiCl2 (5 mol%).The reaction mixture was
stirred overnight at room temperature, and then 10 mL of aqueous NH4Cl
solution was added.The reaction solution was diluted with ethyl acetate
(30 mL), washed with brine (30 mL Â 3), and dried over anhydrous sodium
sulfate.The crude product was purified through a silica gel column.
In summary, we have developed a new simple method for the direct
synthesis of ꢀ-aryl-ꢁ,ꢀ-unsaturated amides from benzyl alcohols and N,N-
dimethylacetamide.This process displays high stereoselectivity.Efforts to
extend the substrate scope to other classes of substrates are currently in
progress.
ACKNOWLEDGMENTS
This work was financially supported by the National Natural Science
Foundation of China (29972037) and Foundation for University Key
Teacher by the Ministry of Education.We are grateful to Dr.Yuan-Jiang
Pan for 500 MHz NMR measurements.
REFERENCES AND NOTES
1. Peterson, K.P.; Larock, R.C. J. Org. Chem. 1998, 63, 3185–3189.
2. Nishimura, T.; Onoue, T.; Ohe, K.; Uemura, S. Tetrahedron Lett. 1998,
39, 6011–6014.
3. Nishimura, T.; Hashizume, T.; Mori, K.; Ohe, K.; Uemura, S. J. Org.
Chem. 1999, 64, 9374–9380.

1204
REN AND WANG
4. Barak, G.; Dakka, J.; Sasson, Y. J. Org. Chem. 1988, 53, 3553–3555.
5. Tamaru, Y.; Inoue, K.; Yamada, Y.; Yoshida, Z. Tetrahedron Lett.
1981, 22, 1801–1804.
6. Nagashima, H.; Sato, K.; Tsuji, J. Tetrahedron 1985, 41, 5645–5651.
7.Aı t-Mohand, S.; Henin, F.; Muzart, J. Tetrahedron Lett. 1995, 36,
2473–2476.
8. Minami, I.; Shimizu, I.; Tsuji, J. J. Organomet. Chem. 1985, 296,
269–280.
9. Gomez-Bengoa, E.; Noheda, P.; Echavarren, A.M. Tetrahedron Lett.
1994, 35, 7097–7098.
10. Matsunaga, P.T.; Hillhouse, G.L. J. Am. Chem. Soc. 1993, 115,
2075–2077.
11. Matsunaga, P.T.; Mavropoulos, J.C.; Hillhouse, G.L. Polyhedron
1995, 14, 175–185.
12. Bryndza, H.E.; Tam, W. Chem. Rev. 1988, 88, 1163–1188.
13. Mann, G.; Hartwig, J.F. J. Org. Chem. 1997, 62, 5413–5418.
14. Tsou, T.T.; Kochi, J.K. J. Am. Chem. Soc. 1979, 101, 7547–7560.
15. Yamamoto, A.; Yamamoto, T.; Komiya, S.; Ozawa, F. Pure Appl.
Chem. 1984, 56, 1621–1634.
16.Compound 3a: 1H NMR(500 MHz, CDCl3) ꢂ 7.68(d, J ¼ 15.4 Hz, 1H),
7.54(dd, J ¼ 1.8, 8.3 Hz, 2H), 7.36(m, 3H), 6.90(d, J ¼ 15.4 Hz, 1H),
3.19(s, 3H), 3.09(s, 3H) ppm. Compound 3c: 1H NMR(500 MHz,
CDCl3) ꢂ 7.65(d, J ¼ 15.4 Hz, 1H), 7.44(d, J ¼ 8.1 Hz, 2H), 7.18(d,
J ¼ 8.1 Hz, 2H), 6.86(d, J ¼ 15.4 Hz, 1H), 3.18(s, 3H), 3.08(s, 3H),
2.37(s, 3H) ppm. Compound 3e: 1H NMR(500 MHz, CDCl3) ꢂ
7.65(d, J ¼ 15.4 Hz, 1H), 7.25(m, 1H), 6.97(m, 1H), 6.88(d, J ¼ 15.4
Hz, 1H), 6.78(m, 1H), 3.19(s, 3H), 3.08(s, 3H), 2.99(s, 6H) ppm.
17.GC/MS analysis showed that the ratio of 3b/ its Z-isomer is 100/1.0,
the ratio of 3c/its Z-isomer is 100/0.5, and the ratio of 3d/its Z-isomer
is 100/0.8.
Received May 11, 2000