Palladium-catalyzed γ -selective and stereospecific allyl-aryl coupling between allylic acetates and arylboronic acids

Full text of DOI:10.1021/ja808673n

Published on Web 12/03/2008
Palladium-Catalyzed γ-Selective and Stereospecific Allyl-Aryl Coupling
between Allylic Acetates and Arylboronic Acids
Hirohisa Ohmiya, Yusuke Makida, Tatsunori Tanaka, and Masaya Sawamura*
Department of Chemistry, Faculty of Science, Hokkaido UniVersity, Sapporo 060-0810, Japan
Received November 5, 2008; E-mail: sawamura@sci.hokudai.ac.jp
Transition metal catalyzed allylic substitution reactions with carbon
nucleophiles are powerful C-C bond formation methods because of
their broad substrate scopes under mild reaction conditions.1 Charac-
teristic among them are Cu-catalyzed allylic substitutions, which have
excellent γ-regioselectivity. However, these reactions are only possible
with strongly nucleophilic organometallic reagents such as Grignard
or organozinc reagents.2 Also, the reaction of sp2-carbon nucleophiles
such as aryl or alkenylmetal reagents have not been well exploited
due to the poor nucleophilicity of these reagents.3
reaction tolerates a variety of functional groups in both 1 and
arylboronic acids; MeO, CF3, chloride, ketone, aldehyde, ester, and
silyl ether functionalities can be present in the substrates (entries 2-8).
Table 1. Palladium-Catalyzed Reaction of Allylic Acetates with
Arylboronic Acidsa
Herein, we report a new Pd-catalyzed allylic substitution methodol-
ogy, which allows for the reaction of allylic acetates with arylboronic
acids with high γ-selectivity and E/Z-selectivity. The reaction of
optically active allylic acetates having an R-stereogenic center took
place with excellent R-to-γ chirality transfer with syn-selectivity and
gave the corresponding optically active allyl-aryl coupling products
with a stereogenic center at the benzylic position.4-8
The reaction of allylic acetate 1a with phenylboronic acid (1.5 equiv)
in the presence of Pd(OAc)2 (10 mol %), 1,10-phenanthroline (12 mol
%) and AgSbF6 (10 mol %) in 1,2-dichloroethane at 60 °C for 6 h
afforded allyl-aryl coupling product 2a in 80% isolated yield (91%
convn of 1a) with complete regio- (2a/2a′ 100:0) and E/Z- (>20:1)
selectivities (Scheme 1).9,10 Conversely, the reaction of 1a′ afforded
2a′, an isomer of 2a with regard to the R/γ-regioselectivity, with
complete regio- (2a/2a′ 0:100) and E/Z- (>20:1) selectivities. Notably,
the Pd-catalyzed allylic substitution can be performed even under air
without affecting the product yield and selectivities.
Scheme 1
a Conditions: Pd(OAc)2 (10 mol %), 1,10-phenanthroline (12 mol %),
AgSbF6 (10 mol %), 1 (0.50 mmol), arylboronic acid (0.75 mmol),
1,2-dichloroethane (3.0 mL), 60 °C, 12 h. b Isomeric ratios: E/Z > 20:1.
See ref 10. c Isolated yield. d Determined by 1H NMR. e Unreacted
allylic acetate (1) was detected in the crude material by 1H NMR
analysis (entry 1, 40%; entry 6, 14%; entry 11, 15%). f Conditions:
Pd(OAc)2 (5 mol %), 1,10-phenanthroline (10 mol %), AgSbF6 (10 mol
%), 1 (0.50 mmol), PhB(OH)2 (1.0 mmol), THF (3.0 mL), 60 °C, 12 h.
In contrast, the reaction without 1,10-phenanthroline afforded a
complex mixture with no allyl-aryl coupling product (100% convn).
While 2,2′-bipyridyl was as effective as 1,10-phenanthroline (80%
yield), other diamines that we tested were less effective under otherwise
identical conditions. Phosphine ligands inhibited the reaction com-
pletely, giving only a trace of biphenyl. The catalytic reaction even
proceeded without AgSbF6 but with a significantly reduced yield
(54%).
The Pd-catalyzed allyl-aryl coupling can be applied to various
combinations of allylic acetates (1) and arylboronic acids (Table 1).10,11
The reactions afforded the γ-substitution products 2 exclusively (entries
3-13) or predominantly (entries 1 and 2), irrespective of the substitu-
tion patterns of the allylic acetates. Moreover, the reactions took place
with complete E-selectivity (not applicable for 1h, entry 13). The
Table 1 also shows that the efficiency of the reaction is sensitive to
the steric demand of the arylboronic acids and the γ-substituent of 1,
but substantial steric bulk is tolerated at the R-position. For instance,
the reaction of 1a with o-tolylboronic acid is much slower than that
with phenylboronic acid and gave the coupling product 2ab in only
26% yield (entry 1). Furthermore, as the γ-substituent became bulkier
(H < Me < Et < i-Bu), the product yield decreased (Scheme 1 and
Table 1, entries 9-11). On the other hand, allylic acetates 1g and 1h,
bearing a bulky isopropyl group and two methyl groups, respectively,
at the R-position were efficiently coupled with phenylboronic acid
(entries 12 and 13).
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10.1021/ja808673n CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
The reaction of (S)-(E)-1g (97% ee), which has R-i-Pr and γ-Me
substituents, with phenylboronic acid in the presence of Pd(OAc)2,
1,10-phenanthroline, and AgSbF6 gave (R)-(E)-2g with 97% ee,
showing that the allyl-aryl coupling with R-chiral allylic acetates took
place with excellent R-to-γ chirality transfer with syn-selectivity
(Scheme 2).10 The reaction of (S)-(E)-1i (97% ee), which has R-Bu
and γ-Me substituents, with phenylboronic acid gave (R)-(E)-2i with
97% ee, suggesting that the efficiency of the chirality transfer is not
significantly influenced by the steric demand of the R-substituent. On
the other hand, the reaction of (S)-(E)-1j (97% ee), which has R-Hex
and γ-Et groups, afforded (S)-(E)-2j (89% ee) with slightly decreased
enantiomeric purity.
products with a stereogenic center at the benzylic position. Exploration
of the reaction mechanism and development of more advanced catalyst
systems and enantioselective reactions with a chiral catalyst are ongoing
in our laboratory.
Acknowledgment. This work was supported by a MEXT
program, Global COE grant (Project No. B01: Catalysis as the Basis
for Innovation in Materials Science).
Supporting Information Available: Experimental details and
characterization data for new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
References
Scheme 2
(1) (a) Tsuji, J. Acc. Chem. Res. 1969, 2, 144–152. (b) Trost, B. M. Tetrahedron
1977, 33, 2615–2649. (c) Trost, B. M.; Van Vranken, D. L. Chem. ReV.
1996, 96, 395–422.
(2) Even for Cu-catalyzed systems, studies to date have focused largely on
the reactions of primary allylic electrophiles that give terminal alkenes.
For a review on enantioselective allyic substitutions catalyzed by chiral
copper complexes, see: Yorimitsu, H.; Oshima, K. Angew. Chem., Int. Ed.
2005, 44, 4435–4439.
(3) For γ-selective allylic substitution reactions with stoichiometric arylcopper(I)
reagents with excellent 1,3-chirality transfer, see: (a) Harrington-Frost, N.;
Leuser, H.; Calaza, M. I.; Kneisel, F. F.; Knochel, P. Org. Lett. 2003, 5,
2111–2114. (b) Kiyotsuka, Y.; Acharya, H. P.; Katayama, Y.; Hyodo, T.;
Kobayashi, Y. Org. Lett. 2008, 10, 1719–1722.
(4) For related studies from our group (Cu-catalyzed regioselective allylic and
propargylic substitutions with diboron), see: (a) Ito, H.; Kawakami, C.;
Sawamura, M. J. Am. Chem. Soc. 2005, 127, 16034–16035. (b) Ito, H.;
Ito, S.; Sasaki, Y.; Matsuura, K.; Sawamura, M. J. Am. Chem. Soc. 2007,
129, 14856–14857. (c) Ito, H.; Kosaka, Y.; Nonoyama, K.; Sasaki, Y.;
Sawamura, M. Angew. Chem., Int. Ed. 2008, 47, 7424–7427. (d) Ito, H.;
Sasaki, Y.; Sawamura, M. J. Am. Chem. Soc. 2008, 130, 15774-15775.
(5) Pd-catalyzed γ-selective allyl-aryl coupling between aryl iodides and allylic
acetates has been reported. However, the reaction required harsh conditions
(typically 180 °C) and is not stereoselective. See: Mariamphillai, B.; Herse,
C.; Lautens, M. Org. Lett. 2005, 7, 4745–4747.
A possible mechanism for the Pd-catalyzed reaction is proposed in
Scheme 3. First, the reaction of 1,10-phenanthroline-ligated Pd(OAc)2
and AgSbF6 forms the cationic palladium(II) complex A. The catalytic
cycle is initiated by transmetalation between A and an arylboronic
acid to form the (σ-aryl)palladium(II) intermediate B.12 Subsequently,
B forms π-complex C with allylic acetate 1. Then, the π-complex C
undergoes the regioselective C-C double bond insertion into the
aryl-Pd bond with the assistance of intramolecular coordination of
the carbonyl oxygen of the acetoxy group to the cationic Pd center,
forming metallacyclic alkylpalladium(II) D. Finally, ꢀ-acetoxy elimina-
tion, rather than ꢀ-hydride elimination, from D affords coupling product
2 and regenerates A.13
(6) Maddaford reported the Pd-catalyzed C-glycosidation of peracetylated
glycals (γ-substitution of γ-alkoxy-substituted allylic acetates with anti-
stereochemistry) with arylboronic acids. This reaction goes through a (π-
allyl)palladium(II) intermediate. The regioselectivity is controlled by the
electronic effect of the oxygen functionality and is limited to this specific
substrate class. See: Ramanauth, J.; Poulin, O.; Rakhit, S.; Maddaford, S. P.
Org. Lett. 2001, 3, 2013–2015.
Scheme 3. Proposed Mechanism
(7) For Pd-catalyzed allyl-sp2-carbon coupling between allyl alcohol deriva-
tives and organoboron compound via a (π-allyl)palladium(II) intermediate,
see: (a) Miyaura, N.; Yamada, K.; Suginome, H.; Suzuki, A. J. Am. Chem.
Soc. 1985, 107, 972–980. (b) Legros, J.-Y.; Fiaud, J.-C. Tetrahedron Lett.
1990, 31, 7453–7456. (c) Uozumi, Y.; Danjo, H.; Hayashi, T. J. Org. Chem.
1999, 64, 3384–3388, See also ref 6.
(8) For Pd-catalyzed oxidative Mizoroki-Heck-type reactions of allylic acetates
with arylboronic acids, see: (a) Delcamp, J. H.; White, M. C. J. Am. Chem.
Soc. 2006, 128, 15076–15077. (b) Ruan, J.; Li, X.; Saidi, O.; Xiao, J. J. Am.
Chem. Soc. 2008, 130, 2424–2425.
(9) This result is in sharp contrast to the fact that the regioselectivity in the
transition metal catalyzed allylic substitutions that involve a (π-allyl)metal
intermediate is highly dependent on the substitution pattern of allylic
substrates. For reviews on Pd-catalyzed allylic substitution reactions, see
ref 1c. See also ref 7.
(10) For Schemes 1 and 2 and Table 1, the crude materials after removal of the
catalyst and boron compounds consisted of the coupling product (2), biaryl,
unreacted allylic acetate (1), and/or unidentified compounds. The Mizoroki-
Heck-type product was not detected. The isolated products were contami-
nated with traces of unidentified materials (0.1-5%). The isolated yields
for the reaction of 1f,g,h,i in Table 1 and Scheme 2 may be reduced by the
evaporation of the products.
Scheme 4. Proposed Mechanism for the Pd-Catalyzed Allyl-Aryl
Coupling with (S)-(E)-1i and PhB(OH)2
(11) The reaction of terminal alkenes 1d and 1h were carried out with THF
solvent (Table 1, entries 9 and 13). The use of THF suppressed the formation
of unidentified side products.
(12) For a mechanistic study on the formation of a (σ-aryl)palladium(II)
intermediate by transmetalation with arylboronic acid and Pd(OAc)2, see:
Moreno-Man˜as, M.; Pe´rez, M.; Pleixats, R. J. Org. Chem. 1996, 61, 2346–
2351.
(13) (a) Alkene products derived by ꢀ-hydride elimination from alkylpalladium
intermediate D were not observed (see ref 10). This is contradictory with
the reported results of the oxidative Mizoroki-Heck-type arylation of allylic
esters with arylboronic acid. See ref 8. For Mizoroki-Heck-type arylation
of allylic acetates with aryl iodides, see: (b) Pan, D.; Chen, A.; Su, Y.;
Zhou, W.; Li, S.; Jia, W.; Xiao, J.; Liu, Q.; Zhang, L.; Jiao, N. Angew.
Chem., Int. Ed. 2008, 47, 4729–4732.
(14) Since π-complex C (C′) is a normal 16-electron square planar complex,
the acetoxy group of C (C′) should be uncoordinated. Although both
diastereomeric π-complexes may form, the description of equilibrium with
the nonproductive diastereomer is omitted in Scheme 4.
The stereochemical outcome observed in the reaction of the chiral
allylic acetate (S)-(E)-1i can be rationalized by considering the
A1,3-strain in the substrate during the coordination-assisted insertion
(C′ to D′) and the syn-ꢀ-acetoxy elimination (from D′) as shown in
Scheme 4.14
In summary, we have established an air-tolerable, Pd-catalyzed
γ-selective and stereospecific substitution reaction between allylic
acetates and arylboronic acids, which gives allyl-aryl coupling
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