Ruthenium-catalyzed synthesis of Functionalized 1,3-dienes

Article abstract of DOI:10.1021/ol8023488

Functionalized 1,3-diene derivatives have been prepared by regioselective allylation of various nucleophiles with 1,3-dienic carbonates in the presence of a (N,O-carboxylate) allylruthenium precatalyst.

Full text of DOI:10.1021/ol8023488

ORGANIC
LETTERS
2009
Vol. 11, No. 1
185-188
Ruthenium-Catalyzed Synthesis of
Functionalized 1,3-Dienes
Mathieu Achard, Nolwenn Derrien, Hui-Jun Zhang, Bernard Demerseman, and
Christian Bruneau*
UMR 6226, CNRS-UniVersite´ de Rennes 1, Sciences Chimiques-Catalyse et
Organome´talliques, Campus de Beaulieu, 35042 Rennes Cedex, France
christian.bruneau@uniV-rennes1.fr
Received October 14, 2008
ABSTRACT
Functionalized 1,3-diene derivatives have been prepared by regioselective allylation of various nucleophiles with 1,3-dienic carbonates in the
presence of a (N,O-carboxylate) allylruthenium precatalyst.
Allylation reactions catalyzed by transition-metal com-
plexes have attracted much interest as a powerful tool in
organic synthesis for C-C and C-heteroatom bond forma-
tion.1 Recently, ruthenium catalysts have been largely used
in reactions involving unsymmetrical allylic substrates to
promote regioselective formation of branched compounds
containing a chiral center.2,3 Regioselective allylation with
simple allylic substrates such as hexenyl, crotyl, or cinnamyl
derivatives has been studied, but only a few catalytic systems
have been explored to gain access to more highly function-
alized compounds.4 Notably, transition metal-catalyzed al-
lylation reactions involving 1,2-disubstituted allylic substrates
featuring a conjugated diene substructure have received little
attention.5
Herein we report a Cp*Ru-based catalytic system that
allows a regioselective allylation of a variety of nucleophiles
using mono- and dicarbonates to produce functionalized 1,3-
dienes with synthetic potential.5c,6 The 1,3-dienic allylic
substrates involved in this study are represented in Figure 1
along with the tested ruthenium precatalysts [Cp*Ru(MeCN)3]-
[PF6] I,2c,7 [Cp*Ru(t-Bu2-bipy)(MeCN)][PF6] II,3a and [Cp*Ru
(1) (a) Tsuji, J. Transition Metal Reagents and Catalysts: InnoVations
in Organic Synthesis, Wiley: Chichester, 2000; p 109. (b) Trost, B. M.;
Crawley, M. L. Chem. ReV. 2003, 103, 2921. (c) Helmchen, G.; Pfaltz, A.
Acc. Chem. Res. 2000, 33, 336.
(4) (a) Burger, E. C.; Tunge, J. A. Chem. Commun. 2005, 2835. (b)
Austeri, M.; Linder, D.; Lacour, J. Chem. Eur. J. 2008, 14, 5737. (c) Gruber,
S.; Zaitsev, A. B.; Wo¨rle, M.; Pregosin, P. S. Organometallics 2008, 27,
3796. (d) Onitsuka, K.; Okuda, H.; Sasori, H. Angew. Chem., Int. Ed. 2008,
47, 1454.
(2) (a) Zhang, S. W.; Mitsudo, T.; Kondo, T.; Watanabe, Y. J.
Organomet. Chem. 1993, 450, 197. (b) Kondo, T.; Mitsudo, T. In Ruthenium
in Organic Synthesis; S.-I. Murahashi, S.-I., Ed.; Wiley-VCH: Weinheim,
2004; p 129. (c) Trost, B. M.; Fraisse, P. L.; Ball, Z. T. Angew. Chem., Int.
Ed. 2002, 41, 1059. (d) Hermatschweiler, R.; Fernandez, I.; Breher, F.;
Pregosin, P. S.; Veiros, L. F.; Calhorda, M. J. Angew. Chem., Int. Ed. 2005,
(5) (a) Shimizu, I.; Matsumoto, Y.; Nishikawa, M.; Kawahara, T.; Satake,
A.; Yamamoto, A. Chem. Lett. 1998, 983. (b) Gamez, P.; Ariente, C.; Gore´,
J.; Cazes, B. Tetrahedron 1998, 54, 14835. (c) Mori, M.; Tonogaki, K.;
Nishiguchi, N. J. Org. Chem. 2002, 67, 224.
44, 4397
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(6) For selected references see: (a) Han, X.; Corey, E. J. Org. Lett. 1999,
1, 1871. (b) Castagnolo, D.; Renzulli, M. L.; Galletti, E.; Corelli, F.; Botta,
(3) (a) Mbaye, M. D.; Demerseman, B.; Renaud, J.-L.; Toupet, L.;
Bruneau, C. Angew. Chem., Int. Ed. 2003, 42, 5066. (b) Bruneau, C.;
Renaud, J.-L.; Demerseman, B. Chem. Eur. J. 2006, 12, 5178. (c) Zhang,
H.-J.; Demerseman, B.; Toupet, L.; Xi, Z.; Bruneau, C. AdV. Synth. Catal.
M. Tetrahedron: Asymmetry 2005, 16, 2893
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(7) (a) McNair, A. M.; Boyd, D. C.; Mann, K. R. Organometallics 1986,
5, 303. (b) Bruneau, C.; Demerseman, B. e-EROS 2008, DOI: 10.1002/
2008, 350, 1601, and references therein
.
047084289X.rn00810.
10.1021/ol8023488 CCC: $40.75
Published on Web 12/02/2008
2009 American Chemical Society

Allylation of phenol 2a was attempted using a combination
of 1 equiv of the 1,3-dienedicarbonate 1a and 2 equiv of
phenol in the presence of K2CO3 (Table 1). Precatalyst I
bearing three labile acetonitrile ligands (Figure 1) was
inactive and led to the recovery of 1a (entry 1), likely due
to a simple displacement of two acetonitrile ligands in I by
1a acting as a diene,10 generating an unreactive species. The
presence of less labile ligands might be expected to hinder
the coordination of 1a as a diene, and we anticipated that
precatalysts bearing a bipyridine,3a P,O-carboxylate,11 or
N,O-carboxylate ligand,12 which have proven efficiency for
allylation-type reactions, would be more suitable in the case
of diene substrates. Accordingly, the involvement of the
bipyridine complex II as precatalyst showed consumption
of 1a leading, however, to a mixture of B/L/M compounds
(Table 1, entry 2) along with the presence of unidentified
side products.13
Figure 1. Allylic substrates and ruthenium precatalysts.
(2-quinolinecarboxylato)(crotyl)][PF6] III.3c The new 1,3-
dienecarbonates 1a-e were prepared as a rac/meso mixture
(Figure 1) via the well-described enyne cross-metathesis
reaction from the corresponding alkynyl carbonates under
an ethylene atmosphere using the Grubbs’ second-generation
carbene complex [RuCl2(H2IMes)(dCHPh)(PCy3)] IV as
catalyst.5c,8,9
More profitable was the use of precatalyst III, which
resulted in a complete consumption of 1a affording 3a in an
86% isolated yield and noteworthy >98:1:1 B/L/M selectiv-
ity in favor of the disubstituted branched product (entry 3).
The additional presence of a base such as potassium
carbonate was essential to generate the phenoxide anion as
Table 1. Allylation of NuH Using 1,3-Dienedicarbonate 1aa
a All reactions were carried out at 0.05 M concentration in the specified solvent at rt for 14 h under an inert atmosphere with 1a/NuH/[Ru]/K2CO3 in a
b
1/2.2/0.05/2.2 molar ratio. B (branched)/L (linear)/M (mixed) ratio determined by H NMR on the crude mixture. c Isolated yields. d Reaction performed
1
with 1a/NuH/[Ru]/K2CO3 in a 1/1/0.05/2.2 molar ratio.
186
Org. Lett., Vol. 11, No. 1, 2009

Table 2. Ruthenium-Catalyzed Allylation of ArOH with
1,3-Diene Monocarbonates 1b-ea
Table 3. Formation of Functionalized 1,3-Dienes Starting from
Dimethyl Malonate 2d and Pyrrolidine 2ea
a All reactions were carried out at 0.05 M concentration in CH3CN or
CH2Cl2 at rt for 14 h under an inert atmosphere with 1/2/cat. III/K2CO3 in
a 1/1.2/0.05/1.2(0) molar ratio. b B (branched)/L (linear). c Isolated yields.
at the R2 position resulted in lower regioselectivities (88:12
to 95:5) (Table 2, entries 4-6), whereas excellent results
were obtained with dienic compound 1e featuring a phenyl
group at R1 (Table 2, entries 11 and 12).
a All reactions were carried out at 0.05 M concentration in CH3CN at
rt for 14 h under an inert atmosphere with 1/2/cat.III/K2CO3 in a 1/1.2/
0.05/1.2 molar ratio, Ar1) p-methoxyphenyl, Ar2) o-hydroxyphenyl. b B
1
(branched)/L (linear) ratio determined on the crude mixture by H NMR.
c Isolated yields. d 1/2c in a 2.4/1 molar ratio was used.
The allylation of carbonucleophile and amine for the
formation of carbon-carbon and carbon-nitrogen bonds was
then investigated with precatalyst III. Reactions were
conducted at room temperature in acetonitrile for malonate
and dichloromethane without additional base for amines
(Table 3). Under our optimized conditions, in all cases
reactions of dienic substrates 1 with pyrrolidine 2e led to
the exclusive formation of the branched products in satisfac-
tory yields (Table 3, entries 1, 3, 5, and 7). It should be
mentioned that slow degradation was observed after purifica-
tion of these compounds, highlighting their instability.
Under similar conditions but in the presence of K2CO3 to
generate the dimethyl malonate anion, the reaction of dienic
susbtrates 1b and 1c with dimethyl malonate led to the
formation of the allylated compounds with much lower
regioselectivity (Table 3, entries 2 and 4). Moreover, linear
selectivity was observed for the dienic substrate 1d featuring
the n-Pr side chain (Table 3, entry 6). In contrast with these
results, exclusive branched selectivity was demonstrated
nucleophile. Similarly, very high B/L/M selectivities in favor
of the disubstituted branched product were obtained using
acetone, dichloromethane, or dimethylcarbonate (DMC)
(Table 1, entries 4-6). Attempts to react the diacetate analog
of 1a were unsuccessful. Remarkably, such excellent >98:
1:1 B/L/M selectivities in favor of the disubstituted branched
product were also obtained when p-methoxyphenol 2b,
catechol 2c, or dimethyl malonate 2d were used as nucleo-
phile, leading to 3b, the eight-membered ring diether 3c, and
the (bis)alkylated product 3d, respectively (Table 1, entries
7-9). Compounds 3a-d having two stereogenic centers
1
were obtained as rac/meso mixtures analyzed by H NMR.
These promising results also suggested that a new route
was opened for the synthesis of functionalized 1,3-dienes
starting from 1,3-dienic monocarbonate substrates 1b-e. The
scope of this reaction for allylation of various phenols
through the involvement of allylic substrates 1b-e is
summarized in Table 2. Reaction of dienic substrates 1b-e
using precatalyst III led to good regioselectivities in favor
of the corresponding branched ethers 4-7 in good to
excellent isolated yields. High regioselectivities were ob-
tained for the allylation reaction of ArOH with dienic
substrates 1b and 1d featuring an aliphatic side chain (Table
2, entries 1-3 and 7-10). The presence of a phenyl group
(8) (a) Kinoshita, A.; Sakakibara, N.; Mori, M. J. Am. Chem. Soc. 1997,
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Org. Lett., Vol. 11, No. 1, 2009
187

using the dienic substrate 1e, indicating that the regioselec-
tivity strongly depended on the nature of the starting allylic
carbonate (Table 3, entry 8).
Scheme 1. One-Pot Metathesis-Allylation Sequence
Having in hand this method to gain access to functional-
ized dienes, we undertook the preparation of these com-
pounds directly from the corresponding alkynyl carbonates
through one-pot metathesis-allylation catalysis.14 Thus, the
two-step metathesis-allylation sequence was performed in
dimethyl carbonate, allowing the formation of the expected
compound 5a in 45% yield (Scheme 1).
In conclusion, we have shown that the [RuCp*(N,O-
carboxylato)(η3-butenyl)][PF6] complex III is an efficient
catalyst for the functionalization of dienic carbonates via
regioselective allylation reactions. This reactivity reveals for
the first time the ability of a ruthenium catalyst to perform
the activation of 1,2-disubstituted allylic carbonates and their
highly regioselective nucleophilic substitution in favor of
branched isomers, and thus provides a new route to functional
dienes that have potential in both synthesis and polymer
science. The association of ene-yne cross metathesis and
allylation constitutes a straightforward route to new conju-
gated dienes from ethylene, propargylic carbonates, and
nucleophiles.
(9) See Supporting Information for general protocol.
(10) (a) Crocker, M.; Green, M.; Morton, C. E.; Nagle, K. R.; Orpen,
A. G. J. Chem. Soc., Dalton Trans. 1985, 2145. (b) Fagan, P. J.; Mahoney,
W. S.; Calabrese, J. C.; Williams, I. D. Organometallics 1990, 9, 1843. (c)
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5006.
Acknowledgment. The authors are grateful to the MENRT
and CNRS for financial support.
(11) Kawatsura, M.; Ata, F.; Wada, S.; Hayase, S.; Uno, H.; Itoh, T.
Chem. Commun. 2007, 298.
Supporting Information Available: Experimental pro-
cedures and characterization data for compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(12) Saburi, H.; Tanaka, S.; Kitamura, M. Angew. Chem., Int. Ed. 2005,
44, 1730.
(13) In principle, the formation of the B, L, and M regioisomers might
result in the observation of up to seven species due to stereoisomerism.
(14) For allylic alkylation-RCM sequence see: Kammerer, C.; Prestat,
G.; Gaillard, T.; Madec, D.; Poli, G. Org. Lett. 2008, 10, 405.
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