Intermolecular heck-type coupling of aryl iodides and allylic acetates

Article abstract of DOI:10.1021/ol051947e

(Chemical Equation Presented) A palladium-catalyzed arylation of allylic acetates followed by β-acetoxy elimination was shown to produce Heck-type coupling products. Optimal reaction conditions employed ligand-free palladium on carbon in the presence of tetrabutylammonium chloride, a trialkylamine base, and water.

Full text of DOI:10.1021/ol051947e

ORGANIC
LETTERS
2005
Vol. 7, No. 21
4745-4747
Intermolecular Heck-Type Coupling of
Aryl Iodides and Allylic Acetates
Brian Mariampillai, Christelle Herse, and Mark Lautens*
DaVenport Research Laboratories, Department of Chemistry, UniVersity of Toronto,
Toronto, Ontario, Canada M5S 3H6
mlautens@chem.utoronto.ca
Received August 11, 2005
ABSTRACT
A palladium-catalyzed arylation of allylic acetates followed by
â-acetoxy elimination was shown to produce Heck-type coupling products.
Optimal reaction conditions employed ligand-free palladium on carbon in the presence of tetrabutylammonium chloride, a trialkylamine base,
and water.
Palladium-catalyzed coupling reactions are among the most
useful synthetic methods for the formation of carbon-carbon
and carbon-heteroatom bonds.1 Included within this general
class is the Heck reaction,2 which has received a substantial
amount of interest since its initial report.3 Recently, we
reported the intramolecular Heck-type coupling of aryl
iodides and allylic acetates/carbonates.4 â-Acetoxy elimina-
tion occurs preferentially over â-hydride elimination, produc-
ing olefinic products. Methods for the intermolecular cou-
pling of allylic acetates and aryl iodides have been previously
reported; however, these methods require stoichiometric
amounts of metal additives to form nucleophilic reagents in
situ.5 Herein, we report a method for aryl-allyl intermo-
lecular coupling between aryl iodides and allylic acetates.
1-Iodonaphthalene 1 and allyl acetate were reacted with
use of our previously optimized conditions for the intramo-
lecular reaction (Scheme 1).
While a low yield of the desired product 2 was obtained,
examination of other allyl leaving groups gave even poorer
results (Table 1). We then examined the effect of the catalyst
and additives.
(1) Tsuji, J. Palladium Reagents and Catalysts: New PerspectiVes for
the 21st Century; Wiley: Chichester, UK, 2004.
(2) (a) Mizoroki, T.; Mori, K. Bull. Chem. Soc. Jpn. 1971, 44, 581. (b)
Mizoroki, T.; Mori, K. Bull. Chem. Soc. Jpn. 1973, 46, 1505-1508. (c)
Heck, R. F.; Nolley, J. P., Jr. J. Org. Chem. 1972, 37, 2320-2322. (d)
Dieck, H. A.; Heck, R. F. J. Am. Chem. Soc. 1974, 96, 1133-1136.
(3) (a) Heck, R. F. Palladium Reagents in Organic Synthesis; Academic
Press: New York, 1985. (b) Trost, B. M.; Verhoeven, T. R. In Compre-
hensiVe Organometallic Chemistry; Wilkinson, G., Stone, F. G., Abel, E.
W., Eds.; Pergamon: Oxford, UK, 1982; Vol. 8, pp 799-938. (c) Farina,
V. In ComprehensiVe Organometallic Chemistry II; Wilkinson, G., Stone,
F. G., Abel, E. W., Eds.; Pergamon: Oxford, UK, 1995; Vol. 12, pp 161-
240. (d) Metal-Catalyzed Cross-coupling Reactions; Diederich, F., Stang,
P. J., Eds.; Wiley-VCH: Weinheim, Germany, 1998. (e) Hegedus, L. S. In
Organometallics in Synthesis: A Manual; Schlosser, M., Ed.; Wiley:
Chichester, UK, 1994; Chapter 5. (f) Link, J. T. In Organic Reactions;
Overman, L. E., Ed.; Wiley: Hoboken, NJ, 2002; Vol. 60, pp 157-534
and references therein.
Scheme 1. Initial Coupling Experiments
(4) Lautens, M.; Tayama, E.; Herse, C. J. Am. Chem. Soc. 2005, 127,
72-73.
10.1021/ol051947e CCC: $30.25
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Published on Web 09/21/2005

Table 1. Investigation of Leaving Groups for the
Intermolecular Heck-Type Coupling Reactiona
Table 2. Heck-Type Coupling of Allyl Acetate with Various
Aryl Iodidesa
a Conditions: aryl iodide (1.0 equiv), allylic acetate (2.0 equiv), Pd2(dba)3
(5 mol %), (o-tolyl)3P (22 mol %), n-BuMe2N (2.0 equiv), CH3CN-H2O,
10:1, 160 °C in microwave reactor. b NMR yield, mesitylene used as internal
standard.
Optimization of the palladium catalyst showed palladium
on carbon to be the catalyst of choice (Scheme 2). The use
of phosphine ligands in the reaction provided low yields of
2; however, other ligand free palladium sources such as
palladium acetate led to complete conversion of the starting
material.
Scheme 2. Optimized Coupling Conditions
A number of tetrabutylammonium salts were also screened
as additives for the reaction. It was found that tetrabutylam-
monium chloride increased the conversion of the reaction
similarly to the ligand-free Heck coupling reported by
Jeffery.6
a Conditions: aryl iodide (1.0 equiv), allylic acetate (3.0 equiv),
Bu4NCl‚xH2O (3.0 equiv), n-BuMe2N (4.0 equiv), 10% Pd/carbon (1 mol
%), H2O (1.0 equiv), DMF, 180 °C sealed tube, 3 h except as noted. b All
yields refer to isolated, pure products. c Reaction heated for 8 h. d Reaction
heated for 1 h with 10% Pd/carbon (5 mol %). e 18% of internal olefin
observed.
The reaction scope was explored under the optimized
conditions. We began by examining the aryl iodide partner
(Table 2). Electron donating groups (entry 5) led to increased
reaction times, presumably due to slower oxidative addition
of palladium into the aryl iodine bond.1 Substrates bearing
electron withdrawing substituents required shorter reaction
times. However, in these cases rapid isomerization of the
alkene to the thermodynamically more stable styrenyl system
occurred under the reaction conditions (entries 6 and 8). In
the case of an ester in the para position 13 (entry 7) the
terminal olefin 14 could be isolated when 5 mol % of
palladium was used. Both aryl chlorides and bromides
(entries 2 and 3) were stable under the reaction conditions,
providing a useful handle for further functionalization of the
products.
(5) (a) Yokoyama, Y.; Ito, S.; Takahashi, Y.; Murakami, Y. Tetrahedron
Lett. 1985, 26, 6457-6460. (b) Trost, B. M.; Walchli, R. J. Am. Chem.
Soc. 1987, 109, 3487-3488. (c) Ikegami, R.; Koresawa, A.; Shibata, T.;
Takagi, K. J. Org. Chem. 2003, 68, 2195-2199. (d) Lee, P. H.; Sung, S.-
Y.; Lee, K. Org. Lett. 2001, 3, 3201-3204.
(6) Jeffery, T. Tetrahedron 1996, 52, 10113-10130.
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Org. Lett., Vol. 7, No. 21, 2005

We next turned our attention to the range of allylic acetates
that participate in the reaction (Table 3). As with most Heck
(entries 3-5). Olefin selectivity was dependent upon the size
of the substituent, with larger substituents leading to the less
sterically hindered trans product.
Table 3. Heck-Type Coupling of 1-Iodonaphthalene with
Various Allylic Acetatesa
Scheme 3. Proposed Mechanism for the Heck-Type Coupling
Reaction
A possible mechanism (Scheme 3) for this reaction
involves initial oxidative insertion of palladium into the aryl-
iodine bond of 1 to give 28, followed by carbopalladation
of olefin 29 to give intermediate 30. Intermediate 30 then
undergoes â-acetoxy elimination to give 2. Reduction of Pd-
(II) to Pd(0) is then most likely achieved by coordination of
an amine base followed by â-hydride transfer and reductive
elimination of hydrogen iodide. While a π-allyl-type inter-
mediate could also be postulated, the formation of isomeric
products from isomeric starting materials (entries 1 vs 3)
suggests this is not a dominant process.
In summary, we have developed an intermolecular cou-
pling of aryl iodides and allylic acetates Via a Heck-type
coupling under low palladium catalyst loadings. This pro-
cedure gives rapid access to a range of both terminal and
internal olefins, which can easily be further functionalized.
a Conditions: aryl iodide (1.0 equiv), allylic acetate (3.0 equiv),
Bu4NCl‚xH2O (3.0 equiv), n-BuMe2N (4.0 equiv), 10% Pd/carbon (1 mol
%), H2O (1.0 equiv), DMF, 180 °C sealed tube, 3 h except as noted. b All
yields refer to isolated, pure products. c Reaction heated for 12 h. d 10%
Pd/carbon (10 mol %).
Acknowledgment. We thank Merck Frosst Canada and
the National Sciences and Engineering Research Council of
Canada (NSERC) for support of an Industrial Research Chair,
and the University of Toronto for financial support of this
work.
reactions, substitution on the olefin led to slower reaction
rates and lower yields.1 Interestingly, use of a 1,2-disubsti-
tuted olefin (entry 1) led to the formation of a tertiary center,
which offers the possibility of developing an asymmetric
method. Substitution at the position R to the acetate was also
tolerated and afforded the desired products in good yields
Supporting Information Available: Experimental pro-
cedures and full characterization of all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL051947E
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