Acryloyl chloride: An excellent substrate for cross-metathesis. A one-pot sequence for the synthesis of substituted α,β-unsaturated carbonyl derivatives

Article abstract of DOI:10.1021/ol9021386

"Chemical Equation Presented" A diverse set of functionalized α,β-unsaturated carbonyl compounds were synthesized In good yield by utilizing a very simple one-pot process involving a cross-metathesis between acryloyl chloride and a terminal olefin followed by the addition of a nucleophile.

Full text of DOI:10.1021/ol9021386

ORGANIC
LETTERS
2009
Vol. 11, No. 23
5446-5448
Acryloyl Chloride: An Excellent
Substrate for Cross-Metathesis. A
One-Pot Sequence for the Synthesis of
Substituted r,ꢀ-Unsaturated Carbonyl
Derivatives
Laurent Ferrie´,† Samir Bouzbouz,*,‡ and Janine Cossy*,†
Laboratoire de Chimie Organique ESPCI ParisTech, CNRS, 10 rue Vauquelin,
75231 Paris Cedex 05, France, and Laboratoire de Chimie Organique CNRS COBRA
UMR 6014, UniVersite´ de Rouen, 76183 Rouen Cedex 03, France
janine.cossy@espci.fr; samir.bouzbouz@uniV-rouen.fr
Received September 16, 2009
ABSTRACT
A diverse set of functionalized r,ꢀ-unsaturated carbonyl compounds were synthesized in good yield by utilizing a very simple one-pot process
involving a cross-metathesis between acryloyl chloride and a terminal olefin followed by the addition of a nucleophile.
One of the challenges in synthetic chemistry is the develop-
ment of reactions and strategies that allow a facile conversion
of simple and inexpensive compounds into complex
molecules, while keeping in mind the principle of atom
economy. One of these reactions is olefin metathesis, which
has emerged as a powerful synthetic tool due to the
development of active, selective, and stable catalysts. The
most common catalysts used are [Ru]-I,1 [Ru]-II,2 [Ru]-III3
and, to a lesser extent, [Ru]-IV4 (Figure 1).
Cross-metathesis (CM) is commonly used to form CdC
bonds under mild conditions, and by using this reaction, even
Figure 1. Ruthenium catalysts.
trisubstituted and functionalized olefins can be synthesized.
However, cross-metathesis has some limitations as, for
example, the efficiency of the CM between R,ꢀ-unsaturated
amides and terminal olefins depends on the nitrogen sub-
stituents of the amide group. It is worth noting that the
presence of electron-donating substituents on the nitrogen
of R,ꢀ-unsaturated amides, such as alkyl groups, results in
low yields in CM products.5
† ESPCI ParisTech.
‡ Universite´ de Rouen.
Here, we report a two-step one-pot process that allows
the synthesis of R,ꢀ-unsaturated amides in good to excellent
yields by realizing a cross-metathesis between acryloyl
(1) (a) Schwab, P.; France, M. B.; Ziller, J. W.; Grubbs, R. H. Angew.
Chem., Int. Ed. 1995, 34, 2039. (b) Schwab, P.; Grubbs, R. R.; Ziller, J. W.
J. Am. Chem. Soc. 1996, 118, 100.
10.1021/ol9021386 CCC: $xxxx
Published on Web 11/09/2009
 2009 American Chemical Society

chloride 1 and terminal olefins followed by the addition of
various amines on the formed intermediate A (Scheme 1).
traces of 3a were observed (Table 1, entry 1) and by using with
[Ru]-II, a low yield in 3a was obtained (19%) (Table 1, entry
2). On the contrary, when the reaction was performed in
refluxing CH2Cl2 in the presence of [Ru]-II, 3a was produced
in good yield (74%) (Table 1, entry 3). It was also noticed that
[Ru]-III was more efficient than [Ru]-II as 3a was isolated with
a similar yield when the reaction was performed at rt (73%
yield versus 74% yield) (Table, entries 3 and 4). It is worth
noting that by using [Ru]-IV at rt, 3a was obtained in only
54% (Table 1, entry 5). Because of these results, all the reactions
were performed with [Ru]-III at rt. This one-pot sequence CM/
addition of amines is general. When a secondary amine (N-
methylamine) and ammonia were added after completion of
the CM between acryloyl chloride 1 and olefin 2, the corre-
sponding amides 3b,c (Table 1, entries 6 and 7) were isolated
in good yields (80-81%). This process is more efficient than
the CM between primary, secondary, or tertiary acrylamides
and olefin 2, as yields of 3 depend on the substituents on the
nitrogen atom of acrylamides (Table 1, entries 8-10). For
comparison with our one-pot sequence, the CM between
acrylamide 4c and 2 gave good yield in 3c, whereas the yield
in the CM product using N-methylacrylamide 4b and 2 dropped
dramatically and the CM was inefficient with N,N-dimethy-
lacrylamide 4a. These results are in agreement with the results
already reported in the literature.5
Scheme 1. One-Pot Sequence CM/Nucleophile Addition
Furthermore, addition of various nucleophiles, such as
alcohols or sodium azide, on the very reactive CM interme-
diate A provides R,ꢀ-unsaturated esters and R,ꢀ-unsaturated
azides respectively (products B) (Scheme 1).
In order to synthesize N,N-dialkyl R,ꢀ-unsaturated amides,
preliminary CM studies were achieved with freshly distilled
acryloyl chloride 1 (1.5 equiv) and olefin 2 (1 equiv) in the
presence of a ruthenium catalyst (5 mol %) in CH2Cl2, at a
concentration of 0.2 M, at rt. After 16 h, N,N-dimethylamine
(33% in ethanol) was added to the reaction media and the
mixture was purified by flash chromatography on silica gel
chromatography to afford 3a. Four different catalysts were
screened in order to obtain the best yields in olefin 3a. The
results are summarized in Table 1.
Different olefin partners were examined, and the results
are reported in Table 2.
Table 1. Screening of Ruthenium Catalystsa
Table 2. Terminal Olefin Partnersa
entry
[Ru]
temp (°C)
R
HX
product yieldb (%)
c
c
c
c
c
1
2
3
4
5
6
7
8
9
[Ru]-I
rt
rt
40 °C
rt
rt
rt
rt
rt
rt
Cl
Cl
Cl
Cl
Cl
Cl
Cl
HNMe2
HNMe2
HNMe2
HNMe2
HNMe2
3a
3a
3a
3a
3a
3b
3c
3c
3b
3a
traces
19
74
73
54
80
81
71
11
[Ru]-II
[Ru]-II
[Ru]-III
[Ru]-IV
[Ru]-III
[Ru]-III
[Ru]-III
[Ru]-III
H2NMec
H3Nd
none
NH2
NHMe none
NMe2 none
10 [Ru]-III
rt
traces
a Conditions: [Ru] catalyst (5 mol %), terminal olefin (1 equiv), 1 or
4a-c (1.5 equiv), CH2Cl2 0.2 M, 16 h then amine (6 equiv), 1 h. b Yields
of isolated products. c Amine solution, 33% in EtOH. d NH3 28% in H2O.
TBS ) tert-butyldimethylsilyl.
a Conditions: [Ru]-III catalyst (5 mol %), terminal olefin (1 equiv), 1
(1.5 equiv), CH2Cl2 0.2 M, 16 h then piperidine (6 equiv), 1 h. b Yields of
isolated products.
At first, the one-pot sequence was performed, at rt, with [Ru]-I
and [Ru]-II (Table 1, entries 1 and 2). By using [Ru]-I, only
(2) (a) Huang, J.; Stevens, E. D.; Nolan, S. P.; Peterson, J. L. J. Am.
Chem. Soc. 1999, 121, 2674. (b) Scholl, M.; Trnka, T. M.; Morgan, J. P.;
Grubbs, R. H. Tetrahedron Lett. 1999, 40, 2247. (c) Weskamp, T.; Kohl,
F. J.; Hieringer, W.; Gleich, D. W.; Herrmann, A. Angew. Chem., Int. Ed.
1999, 38, 2416. (d) Huang, J.; Schanz, H. J.; Stevens, E. D.; Nolan, S. P.
Organometallics 1999, 18, 5375. (e) Scholl, M.; Ding, S.; Lee, C. W.;
Grubbs, R. H. Org. Lett. 1999, 1, 953.
This one-pot CM/nucleophile addition sequence using acryloyl
chloride 1 and various electron-rich terminal olefin partners
followed by the addition of piperidine were screened. Good to
excellent yields in CM products 5-8 were obtained (Table 2).
Org. Lett., Vol. 11, No. 23, 2009
5447

We have to point out that this reaction seems to be limited
to the utilization of Type I olefins (in the Grubbs olefin
classification)6 as allyl acetate and methyl-2-pentene do not
produce the corresponding CM product. The addition of
various amines to intermediate A was realized, and excellent
yields in the corresponding substituted acrylamides were
obtained (65-81%) (Table 3). It is worth noting that when
cheap amines were utilized, a large excess of the amine was
introduced in the reaction mixture (Table 3, entries 4-5).
In the case of more valuable amines, 1.6 equiv of amine
was added to the reaction media as well as an additive, K3PO4
(3.8 equiv)7 (Table 3, entries 1, 2, 6, and 78). When amine
hydrochlorides were used, including Weinreb amine hydro-
chloride,9 the best results in substituted acrylamides were
obtained when N-methylmorpholine was introduced in the
reaction media (Table 3, entries 3, 8, and 9).
The CM products resulting from acryloyl chloride 1 and
olefin 2 can also be trapped with nucleophiles other than amines
such as allylic and propargylic alcohols. The corresponding
esters 3m and 3n were formed in good yields (63-65%) at 0
°C in the presence of pyridine (Table 3, entries 10 and 11).
Sodium azide is also able to react with intermediate A as
the azido derivative 3o was formed in 63% yield (Table 3,
entry 12). It is worth noting that 9 is unstable and cannot be
used to prepare 3o (Scheme 2);10 the latter can be a useful
intermediate for the preparation of vinyl isocyanates.11
Table 3. Addition of Various Nucleophilesa
Scheme 2
In conclusion, a very simple one-pot process involving a CM
between acryloyl chloride and terminal olefins followed by the
addition of nucleophiles leads to a diversity of functionalized
R,ꢀ-unsaturated carbonyl compounds in good yields. Extension
to other nucleophiles and the use of this one-pot sequence to
synthesize a library of biologically active compounds is
underway in our laboratory and will be reported in due course.
Supporting Information Available: General procedure
for the cross-metathesis reactions and 1H NMR and 13C NMR
spectra of all new compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
OL9021386
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a Conditions: [Ru]-III catalyst (5 mol %), 2 (1 equiv), 1 (1.5 equiv),
CH2Cl2 0.2 M, 16 h then nucleophile, quench additive 1 h. b Yields of
isolated products. c 1.6 equiv of amine. d 6 equiv of amine. e 3 equiv of
alcohol 0 °C. f Reaction performed in toluene followed by addition of dry
MeCN (0.2 M), 3 equiv of NaN3 (3 equiv), 2 h stirring. NMM )
N-methylmorpholine. TBS ) tert-butyldimethylsilyl.
5448
Org. Lett., Vol. 11, No. 23, 2009