γ-Selective cross-coupling reactions of potassium allyltrifluoroborates with haloarenes catalyzed by a Pd(0)/D-t-BPF or Pd(0)/Josiphos ((R,S)-CyPF-t-Bu) complex: Mechanistic studies on transmetalation and enantioselection

Article abstract of DOI:10.1021/om800832r

Cross-coupling between bromoarenes and [(E)-CH₃CH=CHCH ₂BF₃]K (2a) by a catalyst prepared from Pd(OAc) ₂ and D-t-BPF selectively provided γ-coupling products via S_E2' substitution. Mechanistic study o

Full text of DOI:10.1021/om800832r

152
Organometallics 2009, 28, 152–160
γ-Selective Cross-Coupling Reactions of Potassium
Allyltrifluoroborates with Haloarenes Catalyzed by a Pd(0)/D-t-BPF
or Pd(0)/Josiphos ((R,S)-CyPF-t-Bu) Complex: Mechanistic Studies
on Transmetalation and Enantioselection
Yasunori Yamamoto,* Shingo Takada, and Norio Miyaura*
DiVision of Chemical Process Engineering, Graduate School of Engineering, Hokkaido UniVersity,
Sapporo 060-8628, Japan
Tetsuji Iyama and Hiroto Tachikawa
DiVision of Materials Chemistry, Graduate School of Engineering, Hokkaido UniVersity,
Sapporo 060-8628, Japan
ReceiVed August 27, 2008
Cross-coupling between bromoarenes and [(E)-CH3CH)CHCH2BF3]K (2a) by a catalyst prepared from
Pd(OAc)2 and D-t-BPF selectively provided γ-coupling products via SE2′ substitution. Mechanistic study
of transmetalation revealed a heretofore unknown process, namely, formation of a highly electrophilic
[Pd(Ar)(D-t-BPF)]+ before transmetalation with 2a. Thus, kinetic data in coupling of 4-substituted
bromoarenes with 2a showed a linear positive correlation (F ) -1.1) accelerated by donating substituents.
This rate-determining role of transmetalation was further confirmed by kinetic data between oxidative
adducts [Pd(Ar)(Br)(D-t-BPF)] and 2a that exhibited an analogous correlation with a negative F-value
(-0.50). Theoretical study by density functional theory (DFT) calculation showed that transmetalation
between [Ar-Pd]+ and 2a via an SE2′ (open) transition state is a slightly lower energy process than an
SE2′ (closed) process. Allylic substitutions with chiral catalysts are the current topics for enantioselective
C-C bond formation, but the catalysts that are effective for allylic nucleophiles have remained unexplored.
Among the ligands screened, (R,S)-CyPF-t-Bu was found to achieve 77-90% ee for representative para-
and meta-substituted bromoarenes and 2-bromo-1-alkenes in refluxing aqueous tetrahydrofuran (THF)
or MeOH. To obtain mechanistic information on enantioselection, the mode of substrate coordination to
a cationic phenylpalladium intermediate was calculated, that is, the reaction stage directly preceding the
stereodetermining insertion step by DFT calculation. A stable adduct between [Pd(CyPF-t-Bu)(Ph)]+
and 2a located at the C-C double bond from its re-face yielding the experimentally observed R-product
is preferred thermodynamically rather than the corresponding si-coordination.
allyltrifluorosilanes and haloarenes.6a,c The coupling selectively
occurred at the γ-carbon when using PPh3 or bisphosphines
Introduction
Transition-metal-catalyzed cross-coupling reactions have
proved to be one of the most powerful methods for selective
C-C bond formation.1 Among the possible combinations of
electrophiles and nucleophiles, reactions of allylic metals with
aryl, alkenyl, and allyl electrophiles or with their reversed
combination provide an important class of compounds because
of the frequent occurrence of allylic fragments in natural
products.2 The coupling reactions of allylmagnesium,3 -zinc,4
-boron,5 -silicon,6 -tin,7 and -zirconium8 compounds with Ni
and Pd catalysts have been extensively studied. Perfect control
of the coupling position by phosphine ligands was first achieved
by Hatanaka and Hiyama et al. using a combination of
possessing a large bite angle such as 1,4-bis(diphenylphosphi-
no)butane (dppb), whereas bisphosphines possessing a relatively
small angle such as 1,3-bis(diphenylphosphino)propane (dppp)
underwent selective coupling at the R-carbon. Such an effect
of phosphine ligands was also demonstrated in regioselective
Stille coupling of aryl halides with Me3SiCH2CH)CHCH2-
SnBu3 at the R- or γ-carbon.7g There have been very few
attempts to employ allylboron compounds, but boron reagents
have various advantages, including availability, air and moisture
stability, low toxicity, and easy removal of boron-derived
byproducts. We have reported the efficiency of potassium
allyltrifluoroborates for perfect γ-selective coupling with bro-
* To whom correspondence should be addressed. Tel/fax: +81-11-706-
6561; e-mail: yasuyama@eng.hokudai.ac.jp (Y.Y.) and miyaura@
eng.hokudai.ac.jp.
(2) (a) Heck, R. H. J. Am. Chem. Soc. 1968, 90, 5531. (b) Negishi,
E.-i.; Chatterjee, S.; Matsushita, H. Tetrahedron Lett. 1981, 22, 3737. (c)
Legros, J.-Y.; Flaud, J.-C. Tetrahedron Lett. 1990, 31, 7453. (d) Mareno-
Man˜as, M.; Pajuelo, F.; Pleixats, R. J. Org. Chem. 1995, 60, 2396. (e)
Chung, K.-G.; Miyake, Y.; Uemura, S. J. Chem. Soc., Perkin Trans. 1 2000,
2725. (f) Bouyssi, D.; Gerusz, V.; Balme, G. Eur. J. Org. Chem. 2002,
2445. (g) Ikegami, R.; Koresawa, A.; Shibata, T.; Takagi, K. J. Org. Chem.
2003, 68, 2195. (h) Kayaki, Y.; Koda, T.; Ikariya, T. Eur. J. Org. Chem.
2004, 4989. (i) Tsukamoto, H.; Sato, M.; Kondo, Y. Chem. Commun. 2004,
1200.
(1) For reviews, see: (a) Boronic Acids; Hall, D. G., Ed.; Wiley-VCH:
Weinheim, Germany, 2005. (b) Metal-Catalyzed Cross-Coupling Reactions,
2nd ed.; de Meijere, A., Diederich, F., Eds.; Wiley-VCH: Weinheim,
Germany, 2004. (c) Cross-Coupling Reactions. A Practical Guide; Miyaura,
N., Ed.; Springer: Berlin, 2002. (d) Handbook of Organopalladium
Chemistry for Organic Synthesis; Negishi, E.-I., Ed.; John Wiley & Sons:
New York, 2002. (e) Metal-Catalyzed Cross-Coupling Reactions; Diederich,
F., Stang, P. J., Eds.; Wiley-VHC: Weinheim, Germany, 1998.
10.1021/om800832r CCC: $40.75
2009 American Chemical Society
Publication on Web 11/24/2008

Transmetalation and Enantioselection Studies
Organometallics, Vol. 28, No. 1, 2009 153
moarenes and bromoalkenes9 and their asymmetric coupling
with bromoarenes using (R,S)-CyPF-t-Bu as the chiral auxil-
iary.10 Such a selective γ-coupling was also achieved by Szabo
and co-workers in the synthesis of allylboronic acids via cross-
coupling between diboronic acid and allylic alcohols or vinyl-
cyclopropanes.11 The proposed mechanisms of those γ-selective
coupling reactions of allylic nucleophiles were the SE2′ (open
or closed) process reported for allylsilicon compounds6b and
the addition-elimination process reported for allylboronic
acids,5a,11c,12,13 whereas formation of (π-allyl)palladium(II)
intermediate, which predominates R-coupling, was ruled out.5a
In this paper, we report transmetalation and enantioselection
mechanisms involved in cross-coupling between potassium (E)-
crotyltrifluoroborate and bromoarenes catalyzed by a Pd(0)/D-
t-BPF or Pd(0)/Josiphos ((R,S)-CyPF-t-Bu) complex. Formation
of a cationic palladium(II) intermediate such as [ArPd]+ before
transmetalation was proposed on the basis of results of kinetic
and theoretical studies.
Scheme 1. γ-Selective Coupling Giving 3 (Table 1)
Results and Discussion
tetrahydrofuran (THF) or MeOH in the presence of a palladium
catalyst prepared in situ from Pd(OAc)2 and phosphine ligands.
Since the reaction was very slow in the absence of a base, it
was carried out in a basic solution as was previously reported
in cross-coupling reactions of potassium aryl- and 1-alkenyl-
trifluoroborates.15 The use of K2CO3 (3 equivalents) in anhy-
drous THF gave the best results (85-99% yields), whereas the
use of stronger bases, such as K3PO4 and KOH, resulted in lower
yields (9-30%).
The yields and regioselectivities of the coupling position were
highly sensitive to phosphine ligands employed for palladium
acetate in the reaction of 4-bromoanisole with potassium (E)-
crotyltrifluoroborate (2a) (Table 1). Monodentate PPh3 and
bidentate dppm and dppe possessing a relatively small bite angle
resulted in a mixture of two isomers (entries 1-3), whereas
bisphosphines that have a bite angle larger than dppp yielded a
γ-coupling product (3) as the sole product (entries 4-8). This
effect of bite angle was almost the same as that reported for
allyltrifluorosilanes.6a,c Although these catalysts suffered from
low yields mainly because of formation of anisole derived by
hydrogenolysis of bromoanisole, D-t-BPF16 was finally found
to be the best ligand to achieve high yields and high γ-selectivi-
ties for 4-bromoanisole and methyl 4-bromobenzoate (entries
9-11). This ligand also worked well for a series of allylbor-
onates including (Z)-crotyl- (2b), (E)-cinnamyl-(2c), (E)-3-
methyl-2-pentenyl (2d), (E)-3-methyl-2-heptenyl (2e), allyl (2f),
γ-Selective Coupling Catalyzed by Pd(0)/D-t-BPF. Reaction
between potassium allyltrifluoroborates (2) and bromoarenes
gave γ-coupling products in high yields with perfect regiose-
lectivities for variously functionalized bromoarenes (Scheme 1).9
Air- and water-stable allyltrifluoroborates (2), synthesized by
treatment of allylboronic acids or esters with KHF2, were
advantageous over triallylboranes and allylboronic acids or esters
in preparation and handling of pure and water-stable crystalline
materials.14,15 These K+ salts are highly insoluble in common
organic solvents, but the reaction smoothly proceeded in aqueous
(3) (a) Tsuji, T.; Yorimitsu, H.; Oshima, K. Angew. Chem., Int. Ed. 2002,
41, 4137. (b) Ohmiya, H.; Tsuji, T.; Yorimitsu, H.; Oshima, K. Chem. Eur.
J. 2004, 10, 5640.
(4) (a) Peet, W. G.; Tam, W. J. Chem. Soc., Chem. Commun. 1983,
853. (b) Campbell, J. B.; Firor, J. W.; Davenport, T. W. Synth. Commun.
1989, 19, 2265.
(5) (a) Nilsson, K.; Hallberg, A. Acta Chem. Scand. 1987, B41, 569.
(b) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457. (c) Kalinin, V. N.;
Denisov, F. S.; Bubnov, Y. N. MendeleeV Commun. 1996, 202. (d) Fu¨rstner,
A.; Seidel, G. Synlett 1998, 161. (e) Fu¨rstner, A.; Leitner, A. Synlett 2001,
290. (f) Occhiato, E. G.; Trabocchi, A.; Guarna, A. J. Org. Chem. 2001,
66, 2459. (g) Kotha, S.; Behera, M.; Shah, V. R. Synlett 2005, 1877.
(6) (a) Hatanaka, Y.; Ebina, Y.; Hiyama, T. J. Am. Chem. Soc. 1991,
113, 7075. (b) Hatanaka, Y.; Goda, K.-i.; Hiyama, T. Tetrahedron Lett.
1994, 35, 1279. (c) Hatanaka, Y.; Goda, K.-i.; Hiyama, T. Tetrahedron
Lett. 1994, 35, 6511. (d) Hiyama, T.; Matsuhashi, H.; Fujita, A.; Tanaka,
M.; Hirabayashi, K.; Shimizu, M.; Mori, A. Organometallics 1996, 15, 5762.
(7) (a) Kosugi, M.; Sasazawa, K.; Shimizu; Y.; Migita, T. Chem. Lett.
1977, 6, 301. (b) Trost, B. M.; Keinan, E. Tetrahedron Lett. 1980, 21, 2595.
(c) Godschalx, J.; Stille, J. K. Tetrahedron Lett. 1980, 21, 2599. (d)
Echavarren, A. M.; Stille, J. K. J. Am. Chem. Soc. 1987, 109, 5478. (e)
Martorell, G.; Garc´ıa-Raso, A.; Saa´, J. M. Tetrahedron Lett. 1990, 31, 2357.
(f) Farina, V.; Krishnan, B. J. Am. Chem. Soc. 1991, 113, 9585. (g) Obora,
Y.; Tsuji, Y.; Kobayashi, M. J. Org. Chem. 1995, 60, 4647. (h) Cotter,
W. D.; Barbour, L.; McNamara, K. L.; Hechter, R.; Lachicotte, R. J. J. Am.
Chem. Soc. 1998, 120, 11016.
(8) Hirano, K.; Yorimitsu, H.; Oshima, K. Synlett 2005, 1787.
(9) Yamamoto, Y.; Takada, S.; Miyaura, N. Chem. Lett. 2006, 35, 704.
(10) Yamamoto, Y.; Takada, S.; Miyaura, N. Chem. Lett. 2006, 35, 1368.
(11) (a) Sebelius, S.; Olsson, V. J.; Szabo´, K. J. J. Am. Chem. Soc. 2005,
127, 10478. (b) Olsson, V. J.; Sebelius, S.; Selander, N.; Szabo´, K. J. J. Am.
Chem. Soc. 2006, 128, 4588. (c) Sebelius, S.; Olsson, V. J.; Wallner, O. A.;
Szabo´, K. J. J. Am. Chem. Soc. 2006, 128, 8150. (d) Dutheuil, G.; Selander,
N.; Szabo´, K. J. Synthesis 2008, 2293.
(15) (a) Darses, S.; Geneˆt, J.-P.; Brayer, J.-L.; Demoute, J.-P. Tetrahe-
dron Lett. 1997, 38, 4393. (b) Darses, S.; Michaud, G.; Geneˆt, J.-P.
Tetrahedron Lett. 1998, 39, 5045. (c) Darses, S.; Michaud, G.; Geneˆt, J.-P.
Eur. J. Org. Chem. 1999, 1875. (d) Batey, R. A.; Thadani, A. N.; Smil,
D. V. Tetrahedron Lett. 1999, 40, 4289. (e) Batey, R. A.; Thadani, A. N.;
Smil, D. V. Synthesis 2000, 990. (f) Batey, R. A.; Quach, T. D. Tetrahedron
Lett. 2001, 42, 9099. (g) Molander, G. A.; Rivero, M. R. Org. Lett. 2002,
4, 107. (h) Thadani, A. N.; Batey, R. A. Org. Lett. 2002, 4, 3827. (i)
Molander, G. A.; Katona, B. W.; Machrouhi, F. J. Org. Chem. 2002, 67,
8416. (j) Molander, G. A.; Bernardi, C. R. J. Org. Chem. 2002, 67, 8424.
(k) Molander, G. A.; Biolatto, B. J. Org. Chem. 2003, 68, 4302. (l)
Molander, G. A.; Yun, C.-S.; Ribagorda, M.; Bilatto, B. J. Org. Chem.
2003, 68, 5534. (m) Barder, T. E.; Buchwald, S. L. Org. Lett. 2004, 6,
2649. (n) Kabalka, G. W.; Dong, G.; Venkataiah, B. Tetrahedron Lett. 2004,
45, 5139. (o) Kabalka, G. W.; Dong, G.; Venkataiah, B. Tetrahedron Lett.
2005, 46, 763. (p) Molander, G. A.; Felix, L. A. J. Org. Chem. 2005, 70,
3950. (q) Kabalka, G. W.; Al-Masum, M. Org. Lett. 2006, 8, 11. (r)
Molander, G. A.; Sommers, E. M.; Baker, S. R. J. Org. Chem. 2006, 71,
1563. (s) Molander, G. A.; Yokoyama, Y. J. Org. Chem. 2006, 71, 2493.
(t) Molander, G. A.; Ham, J.; Seapy, D. G. Tetrahedron 2007, 63, 768.
(16) (a) Itoh, T.; Sato, K.; Mase, T. AdV. Synth. Catal. 2004, 346, 1859.
(b) Itoh, T.; Mase, T. Tetrahedron Lett. 2005, 46, 3573.
(12) Miyaura, N.; Suzuki, A. J. Organomet. Chem. 1981, 213, C53.
(13) (a) Karabelas, K.; Westerlund, C.; Hallberg, A. J. Org. Chem. 1985,
50, 3896. (b) Karabelas, K.; Hallberg, A. J. Org. Chem. 1986, 51, 5286.
(c) Karabelas, K.; Hallberg, A. J. Org. Chem. 1989, 54, 1773. (d) Albe´niz,
A. C.; Espinet, P.; Lo´pez-Ferna´ndez, R. Organometallics 2006, 25, 5449.
(14) (a) Darses, S.; Geneˆt, J.-P. Eur. J. Org. Chem. 2003, 4313. (b)
Molander, G. A.; Ellis, N. Acc. Chem. Res. 2007, 40, 275. (c) Darses, S.;
Geneˆt, J.-P. Chem. ReV. 2008, 108, 288.

154 Organometallics, Vol. 28, No. 1, 2009
Yamamoto et al.
Scheme 2. Asymmetric Coupling Giving 6 (Table 2)
Table 1. γ-Selective Coupling of Potassium Allyltrifluoroborates (2)
with Haloarenes Giving 3 (Scheme 1)
entry
2
ArBr, X )
ligand
PPh3
dppm
dppe
dppp
yield/%a (3/4)
1b
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
2d
2e
2f
4-MeO
4-MeO
4-MeO
4-MeO
4-MeO
4-MeO
4-MeO
4-MeO
42 (78/22)
35 (78/22)
17 (37/63)
37 (>99/1)
68 (>99/1)
21 (>99/1)
10 (>99/1)
10 (>99/1)
87 (>99/1)
85 (>99/1)
99 (>99/1)
91 (>99/1)
99 (>99/1)
96 (>99/1)
99 (>99/1)
99 (-)
2b
3b
4b
5b
dppf
6b
DPEphos
Xantphos
DBFphos
D-t-BPF
D-t-BPF
D-t-BPF
D-t-BPF
D-t-BPF
D-t-BPF
D-t-BPF
D-t-BPF
D-t-BPF
7b
8b
9b
4-MeO
4-MeO
10c
11c
12c
13c
14c
15c
4-CO2Me
4-CO2Me
4-CO2Me
4-CO2Me
4-CO2Me
4-CO2Me
4-CO2Me
16c d
,
17c
2g
99 (<1/99)e
a NMR yields for entries 1-8 and isolated yields for entries 9-17.
b The reactions were conducted for 20 h at reflux in THF-H2O (10/1) in
the presence of Pd(OAc)2 (3 mol %), a ligand (3 mol %), haloarene (0.5
mmol), 2 (0.75 mmol), and K2CO3 (1.5 mmol). c The reactions were
conducted for 22 h at reflux in THF in the presence of Pd(OAc)2 (3 mol
%), a ligand (3.6 mol %), haloarene (1 mmol), 2 (2.5 mmol), and
K2CO3 (3 mmol). d Walphos was used as ligand. e E/Z ) 55/45.
and 1-methyl-2-propenylboronate (2g). Among these boronates
chosen for investigating scope and limitations, it was interesting
that 2d and 2e selectively gave a quaternary carbon (entries 14
and 15) and 2g gave a linear 2-butenyl product via complete
SE2′ substitution (entry 17). Our previous study also showed
that other representative bromoarenes, including hindered 2,6-
dimethyl derivatives and 2-bromo-1-alkenes, achieve γ-selec-
tivities higher than 99%.9 Thus, such high yields and high
γ-selectivity are characteristic for D-t-BPF, which has a large
bite angle and steric hindrance and a strong electron-donating
ability to the palladium(0) metal center.
Asymmetric Coupling Catalyzed by Pd(0)/(R,S)-CyPF-t-
Bu. Transition-metal-catalyzed allylic substitutions with nu-
cleophiles, especially their asymmetric versions using chiral
catalysts, are the current topics.17-19 Several efficient chiral
catalysts have been developed for those purposes and have con-
siderably expanded the scope of enantioselective C-C and
C-heteroatom bond formation. However, chiral catalysts for
allylic nucleophiles have remained unexplored.
Table 2. Asymmetric Coupling of Potassium Crotyltrifluoroborate
(2a) with Methyl 4-Bromobenzoate (1a) (Scheme 2)a
entry
ligand
(R)-BINAP
(S,S)-Et-FerroTANE
(S)-PHANEPHOS
8a
yield/%b
6a/7a
% ee of 6ac
1
2
3
4
5
6
7
8
86
84
63
98
84
96
54
73
57
64
63
93
93
68/32
31/69
84/16
93/7
96/4
92/8
83/17
99/1
83/17
14/86
21/79
95/5
3
12
20 (S)
31 (R)
46 (S)
63 (R)
26 (R)
10
44 (R)
5
4
8b
9a ((R,S)-CyPF-t-Bu)
9b
9c
9d
9e
9f
9
10
11
12d
13e
9a ((R,S)-CyPF-t-Bu)
9a ((R,S)-CyPF-t-Bu)
82 (R)
82 (R)
93/7
a The reactions were conducted at reflux for 22 h in THF in the
presence of Pd(OAc)2 (3 mol %), a ligand (3.6 mol %), methyl
4-bromobenzoate (1 mmol), 2a (2.5 mmol), and K2CO3 (3 mmol).
The regioselectivities of the coupling position (6a, 7a) and
enantioselectivities of 6a were highly sensitive to phosphine
ligands employed for palladium acetate in the reaction between
potassium (E)-crotyltrifluoroborate (2a) and methyl 4-bro-
mobenzoate (Scheme 2 and Table 2). The use of BINAP, Et-
FerroTANE, PHANEPHOS, and other representative C2 sym-
metric chiral phosphines resulted in the formation of two isomers
b Isolated yields. c Enantiomer excess was determined by
a chiral
stationary column. d The reaction in THF-H2O (1/4). e The reaction in
MeOH-H2O (1/9).
with low enantioselectivities (entries 1-3). On the other hand,
the use of ferrocene-type ligands of Mandyphos and Josiphos
series (8 and 9) is dominated by the formation of a γ-coupling
product (6) (entries 4-11). Among the ligands screened, (R,S)-
CyPF-t-Bu (9a) was finally found to be the best ligand to achieve
63% ee with 92% γ-selectivity in refluxing THF (entry 6). The
absolute configuration of 3-(4-methoxycarbonylphenyl)-1-butene
(6a) was established to be R ([R]D - 12.68 (c 0.59, benzene))
by the specific rotation reported for (S)-isomer ([R]D + 12 (c
0.9, CHCl3)) and retention times of two enantiomers in high-
performance liquid chromatography (HPLC) analysis.18d,19b
Allyltrifluoroborates (2) are highly insoluble in common organic
solvents. Thus, addition of water to THF or MeOH resulted in
significant improvement of yields and enantioselectivities
because of the high solubility of 2a in aqueous solvents (entries
12 and 13). The enantioselectivities thus achieved were in the
(17) (a) Hayashi, T. J. Organomet. Chem. 2002, 653, 41. (b) Hayashi,
T.; Tajika, M.; Tamao, K.; Kumada, M. J. Am. Chem. Soc. 1976, 98, 3718.
(c) Hayashi, T.; Konishi, M.; Fukushima, M.; Mise, T.; Kagotani, M.; Tajika,
M.; Kumada, M. J. Am. Chem. Soc. 1982, 104, 180. (d) Hayashi, T.; Konishi,
M.; Fukushima, M.; Kanehira, K.; Hioki, T.; Kumada, M. J. Org. Chem.
1983, 48, 2195.
(18) (a) van Zijl, A. W.; Arnold, L. A.; Minnaard, A. J.; Feringa, B. L.
AdV. Synth. Catal. 2004, 346, 413. (b) Tissot-Croset, K.; Alexakis, A.
Tetrahedron Lett. 2004, 45, 7375. (c) Yorimitsu, H.; Oshima, K. Angew.
Chem., Int. Ed. 2005, 44, 4435. (d) Lo´pez, F.; van Zijl, A. W.; Minnaard,
A. J.; Feringa, B. L. Chem. Commun. 2006, 409.
(19) (a) RajanBabu, T. V.; Nomura, N.; Nandi, J. J. M.; Park, H.; Sun,
X. J. Org. Chem. 2003, 68, 8431. (b) Zhang, A.; RajanBabu, T. V. Org.
Lett. 2004, 6, 1515. (c) Park, H.; Kumareswaran, R.; RajanBabu, T. V.
Tetrahedron 2005, 61, 6352. (d) Shi, W.-J.; Xie, J.-H.; Zhou, Q.-L.
Tetrahedron: Asymmetry 2006, 16, 705.

Transmetalation and Enantioselection Studies
Organometallics, Vol. 28, No. 1, 2009 155
Scheme 3. Hammett Plot Based on Kinetic Data and σ
Scheme 4. Hammett Plot Based on Kinetic Data and σ
Values in the Coupling between 11-15 and 2a
Values in the Reaction between 1 and 2
range of 77-90% ee for representative para- and meta-
substituted bromoarenes and 2-bromo-1-alkenes.10
Kinetic Studies on Transmetalation. The reaction between
2a and para-substituted bromoarenes with Pd(OAc)2/D-t-BPF
in refluxing THF showed Hammett’s correlations suggesting a
rate-determining role of the transmetalation step (Scheme 3).
There were two correlations when the relative rates were
estimated by a competitive reaction of two bromoarenes for 2a
(dotted lines, b and 9). The reactivity linearly was increased
by donating groups having σ-values lower than -0.1 (b, F )
-5.24) and withdrawing groups higher than 4-MeOC6H4Br (9,
F ) 1.05). This result was in sharp contrast to the single
correlation (F ) -1.1) to σ in a range of -0.3 to 0.5 when the
initial rates were estimated by conversions of the independent
runs for each bromoarene (solid line, O). Among the steps
involved in the catalytic cycle of cross-coupling, oxidative
addition exhibits a linear positive correlation accelerated by
withdrawing groups as was observed in most cross-coupling
reactions of arylboronic acids with haloarenes.20 It is difficult
to conclude that this is due to the rate-determining role of
reductive elimination21 because there is no scrambling of the
coupling position between γ-coupling products and thermally
stable linear R-carbon coupling products. Thus, it is reasonable
to conclude that the two correlations shown by the dotted lines
were the result of a balance of the reverse effects of substituents
on oxidative addition and transmetalation. The linear correlation
shown by a solid line is attributable to the electronic effect on
transmetalation.
Five oxidative adducts of bromoarenes, 11-15 (X ) OPh,
H, Cl, CF3, CO2Me), were synthesized by the method of Hartwig
and co-workers22 as intermediates for transmetalation. The
competitive reaction of (E)-crotyltrifluoroborate (2a) with two
oxidative adducts (11-14) in refluxing THF showed a single
correlation with a small negative F-value (-0.50) (Scheme 4).
The CyPF-t-Bu ligand used for asymmetric coupling is also
dominated by the γ-coupling products for formation of a chiral
secondary carbon. The reaction between (E)-crotylborate (2a)
and four oxidative adducts (16-19, X ) OPh, H, Cl, CF3) of
CyPF-t-Bu showed a single correlation with a small negative
F-value (Scheme 5). The slope (-0.70) was almost the same
as that of D-t-BPF ligand.
A possible mechanism that accounts for the electronic effect
of substituents is one proceeding through a cationic palladium(II)
species by elimination of a bromine ligand before reaction with
2a. The expected cationic palladium(II) species (20) was
synthesized by treatment of 15 with AgBF4.22b Indeed, the
reaction between 2a and 20 afforded perfect γ-selectivity
(Scheme 6). The equilibrium formation of [Pd(Ar)(D-t-BPF)]+
from Pd(Ar)(D-t-BPF)(Br) has been reported.22b
(20) (a) Moriya, T.; Miyaura, N.; Suzuki, A. Synlett 1994, 149. (b) Saito,
S.; Oh-tani, S.; Miyaura, N. J. Org. Chem. 1997, 62, 8024. (c) Weissman,
H.; Milstein, D. Chem. Commun. 1999, 1901. (d) Zim, D.; Lando, V. R.;
Dupont, J.; Montiro, A. L. Org. Lett. 2001, 3, 3049. (e) Liang, L.-C.; Chien,
P.-S.; Huang, M.-H. Organometallics 2005, 24, 353.
(21) (a) Temple, J. S.; Riediker, M.; Schwartz, J. J. Am. Chem. Soc.
1982, 104, 1310. (b) Goliaszewski, A.; Schwartz, J. J. Am. Chem. Soc.
1984, 106, 5028. (c) Goliaszewski, A.; Schwartz, J. Organometallics 1985,
4, 417. (d) Bertani, R.; Berton, A.; Carturan, G.; Campostrini, R. J.
Organomet. Chem. 1988, 349, 263.

156 Organometallics, Vol. 28, No. 1, 2009
Yamamoto et al.
Scheme 5. Hammett Plot Based on Kinetic Data and σ
Values in the Reaction between 16-19 and 2a
coupling reaction and Heck coupling reaction have been
reported.23-27 The energy diagram of oxidative addition, Pd-
(PH3)2 (a) + Ph-Br (b) f TSoa f Pd(PH3)2(Ph)(Br) (c), is
given in Figure 1, while the structure of the transition state
(TSoa) is illustrated in Figure 2. The C-Br length of Ph-Br
(b) at the initial separation is calculated to be 1.973 Å. At the
transition state, the C-Br length of TSoa is 2.239 Å, which is
elongated by 0.266 Å by the interaction with Pd. TSoa has a
triangle form composed of a Br-Pd-Ph skeleton with an angle
of 52.3° ( Br-Pd-C). The bond lengths of Pd-Br and Pd-C
of TSoa are 2.774 and 2.136 Å, respectively. The activation
energy at TSoa is 10.2 kcal/mol relative to the initial separation
(zero level) at the B3LYP/LANL2DZ level. The oxidative
adduct, Pd(PH3)2(Ph)(Br), is 26.1 kcal/mol lower in energy than
that of the initial separation, Pd(PH3)2 + Ph-Br. If the solvent
effect is not considered, the energy level of c is slightly larger
than that in THF (-21.2 kcal/mol). The formation of a cationic
palladium(II) species (d) via substitution of the Pd-Br bond
with H2O takes place smoothly with a 13.6 kcal/mol energy
barrier, whereas it is significantly large (100.4 kcal/mol) in the
absence of a solvent effect indicating an important role of the
solvent effect in this charge-separated system. The energy level
of this state composed of (H3P)Pd(Ph)+-OH2 (d) and
CH3CH)CHCH2BF3- (e) is -12.6 kcal/mol lower than that of
the initial state. The coordination of allylboronate (e) to a
cationic palladium(II) complex (d) by the SE2′ (closed) transition
state (f) is +2.0 kcal/mol higher than that by the SE2′ (open)
state (g), though the former state (f′, 10.4 kcal/mol) is 8 kcal/
mol lower than the latter one (g′, +18.4 kcal/mol) in the absence
of a solvent effect. Thus, there is no large difference in energy
levels between SE2′ closed and open coordination, whereas the
SE2′ open process is slightly more stable than the SE2′ closed
process in THF solvent. After TStm, the BF3 group is substituted
by a water molecule for formation of a strong Pd-C bond (h)
with a 30 kcal/mol energy barrier. The structure of the transition
state for transmetalation (TStm) is illustrated in Figure 2. If the
solvent effect is not considered, the energy level of h becomes
higher than zero level (+16.9 kcal/mol). The transition state of
reductive elimination (TSre) has a triangle structure composed
of Pd and two carbon atoms of phenyl and allyl groups as shown
in Figure 2. The energy of TSre is 16.3 kcal/mol higher than
Scheme 6. A Regiochemical Selectivity in the Coupling of
Cationic Complex (20) with 2a
(22) (a) Paul, F.; Patt, J.; Hartwig, J. F. Organometallics 1995, 14, 3030.
(b) Mann, G.; Shelby, Q.; Roy, A. H.; Hartwig, J. F. Organometallics 2003,
22, 2775.
(23) (a) Sumimoto, M.; Iwane, N.; Takahama, T.; Sakaki, S. J. Am.
Chem. Soc. 2004, 126, 10457. (b) Braga, A. A.; Morgon, N. H.; Ujaque,
G.; Maseras, F. J. Am. Chem. Soc. 2005, 127, 9298. (c) Goossen, L. J.;
Koley, D.; Hermann, H. L.; Thiel, W. J. Am. Chem. Soc. 2005, 127, 11102.
(d) Goossen, L. J.; Koley, D.; Hermann, H. L.; Thiel, W. Organometallics
2006, 25, 54. (e) Braga, A. A.; Ujaque, G.; Maseras, F. Organometallics
2006, 25, 3647. (f) Baraga, A. A. C.; Morgon, N. H.; Ujaque, G.; Lledo´s,
A.; Maseras, F. J. Organomet. Chem. 2006, 691, 4459. (g) Sicre, C.; Braga,
A. A. C.; Maseras, F.; Cid, M. M. Tetrahedron 2008, 64, 7437. (h) Huang,
Y.-L.; Weng, C.-M.; Hong, F.-E. Chem. Eur. J. 2008, 14, 4426.
(24) (a) Goossen, L. J.; Koley, D.; Hermann, H. L.; Thiel, W.
Organometallics 2005, 24, 2398. (b) Ahlquist, M.; Norrby, P.-O. Organo-
metallics 2007, 26, 550. (c) Lam, K. C.; Marder, T. B.; Lin, Z. Organo-
metallics 2007, 26, 758. (d) Fazaeli, R.; Ariafard, A.; Jamshidi, S.;
Tabatabaie, E. S.; Pishro, K. A. J. Organomet. Chem. 2007, 692, 3984. (e)
Li, Z.; Guo, Q.-X.; Liu, L. Organometallics 2008, 27, 4043.
(25) (a) Ananikov, V. P.; Musaev, D. G.; Morokuma, K. J. Am. Chem.
Soc. 2002, 124, 2839. (b) Ca´rdenas, D. J.; Echavarren, A. M. New J. Chem.
2004, 28, 338. (c) Ananikov, V. P.; Musaev, D. G.; Morokuma, K. Eur.
J. Inorg. Chem. 2007, 5390.
(26) (a) Lee, M.-T.; Lee, H. M.; Hu, C.-H. Organometallics 2007, 26,
1317. (b) Surawatanawong, P.; Fan, Y.; Hall, M. B. J. Organomet. Chem.
2008, 693, 1552.
Density Functional Theory (DFT) Calculations on the
Energy Diagram of Oxidative Addition, Transmetalation,
and Reductive Elimination Reactions. Results of theoretical
studies on oxidative addition and reductive elimination of cross-
(27) (a) Nova, A.; Ujaque, G.; Maseras, F.; Lledo´s, A.; Espinet, P. J. Am.
´
Chem. Soc. 2006, 128, 14571. (b) Alvarez, R.; Pe´rez, M.; Faza, O. N.; de
Lera, A. R. Organometallics 2008, 27, 3378.

Transmetalation and Enantioselection Studies
Organometallics, Vol. 28, No. 1, 2009 157
Figure 1. DFT calculation of transition state.
Figure 2. Optimized structures of TSoa, TStm, and TSre calculated at the B3LYP/LANL2DZ level.
zero level. In the final state for giving i, the bonding of the
phenyl group (Ph) is changed from Pd to the carbon atom of
allylic carbon, and the Pd atom interacts with the CdC double
bond of H2C)CH(Ph)CH3 (i). The reaction energy is calculated
to be -37.7 kcal/mol, which is large enough to proceed under
thermal conditions.
Proposed Mechanism for Transmetalation. Transmetalation
is a critical process involved in various metal-catalyzed bond-
forming reactions, but the mechanistic features, including its
kinetics, still remain unexplored. Intermediates before trans-
metalation between arylboronic acids and platinum(II) halides
or palladium(II) halides were studied by Osakada28 and
Hartwig.29 We reported the results of a kinetic study of
transmetalation between para-substituted arylboronic acids and
cationic [Pd(Ph)(PPh3)(dppe)]BF4 that showed a small negative
F value (-0.54).30 There have also been theoretical studies on
transmetalation of arylboronic acids and diborons.23 Among
precedents for transmetalation between Ar-Pd-X and al-
lylfluorosilanes, an SE2′ (open) process involving a direct
interaction of the palladium metal center to the C-C double
bond and an SE2′ (closed) process involving an F-chelation
between Pd and Si atoms were proposed on the basis of the
effects of phosphine ligands, the effect of F bases on R- and
γ-coupling selectivity, and the stereochemistry in substitution
of chiral allylsilane compounds.6b On the other hand, the high-
efficiency cationic palladium species for transmetalation has
been demonstrated in the palladium-catalyzed bond-forming
reactions of ArB(OH)2 with ArN2BF4 or Ar2IX (X ) BF4,
OTf)31 and conjugate addition reactions of arylboronic acids to
enones catalyzed by dicationic [Pd(dppe)(PhCN)2](BF4)2.30 The
involvement of such a cationic species in Heck reaction between
aryl triflates and 4-substituted styrenes was demonstrated by a
kinetic study of substituents;32 however, it is not common in
analogous coupling or addition reactions of organic halides.
All kinetic data suggested the formation of a cationic species
(22) as the intermediate for transmetalation with allylborates
(31) (a) Kang, S.-K.; Lee, H.-W.; Jang, S.-B.; Ho, P.-S. J. Org. Chem.
1996, 61, 4720. (b) Sengupta, S.; Bhattacharyya, S. J. Org. Chem. 1997,
62, 3405. (c) Andrus, M. B.; Song, C. Org. Lett. 2001, 3, 3761. (d)
Selvakumar, K.; Zapf, A.; Spannenberg, A.; Beller, M. Chem. Eur. J. 2002,
8, 3901. (e) Dai, M.; Liang, B.; Wang, C.; Chen, J.; Yang, Z. Org. Lett.
2004, 6, 221.
(32) (a) Ozawa, F.; Kubo, A.; Hayashi, T. J. Am. Chem. Soc. 1991,
113, 1417. (b) Cabri, W.; Candiani, I.; DeBernardinis, S.; Francalanci, F.;
Penco, S. J. Org. Chem. 1991, 56, 5796. (c) Ozawa, F.; Kubo, A.;
Matsumoto, Y.; Hayashi, T. Organometallics 1993, 12, 4188.
(28) (a) Osakada, K.; Onodera, H.; Nishihara, Y. Organometallics 2005,
24, 190. (b) Pantcheva, I.; Nishihara, Y.; Osakada, K. Organometallics 2005,
24, 3815. (c) Pantcheva, I.; Osakada, K. Organometallics 2006, 25, 1735.
(d) Suzaki, Y.; Osakada, K. Organometallics 2006, 25, 3251.
(29) Stambuli, J. P.; Bu¨hl, M.; Hartwig, J. F. J. Am. Chem. Soc. 2002,
124, 9346.
(30) Nishikata, T.; Yamamoto, Y.; Miyaura, N. Organometallics 2004,
23, 4317.

158 Organometallics, Vol. 28, No. 1, 2009
Yamamoto et al.
Scheme 7. Formation of a Cationic Palladium(II) Species
(22) before Transmetalation with 2a
Scheme 8. DFT Calculation of SE2 (Open) Conformation at
Minimam Energy Level
(2) when bulky and donating D-t-BPF was used as the ligand
(Scheme 7). Since the reaction resulted in perfect γ-selectivities
for all bromoarenes, the formation of an allylic π-complex
intermediate before reductive elimination or an addition-
elimination mechanism between Ar-Pd-X and the double bond
of 2a is ruled out. On the basis of these mechanistic precedents,
our kinetic and theoretical calculation results, it was concluded
that the formation of a π-complex (23) via coordination of the
C-C double bond of 2a to 22 is the most probable transition
state that selectively gives γ-coupling products (6) via σ-al-
lylpalladium(II) intermediates (25). A chelated cyclic complex
(24) via coordination of F and a C-C double bond is another
probable process, but the theoretical study indicated that the F
chelation does not affect the stability of the transition state.
Enantioselection Mechanism in Asymmetric Coupling. The
X-ray structure of [Pd(CyPF-t-Bu)(4-MeOC6H4)(NH3)]OTf (27)
reported by Shen and Hartwig is shown in Figure 3.33 The
molecular structure displays a slightly twisted square-planar
coordination geometry for the palladium(II) atom ligated with
two phosphorus atoms of (R,S)-CyPF-t-Bu, one carbon atom
of the 4-methoxyphenyl group and one nitrogen atom of NH3.
There is a steric hindrance to pressure the right NH3 upward
and the left 4-methoxyphenyl group downward with respect to
the P-Pd-P plane thus suggesting that the free space is
accessible to reactants in the upper-right and lower-left quad-
rants. The dihedral angle between the P-Pd-P and C-Pd-N
plane is 18.9° with anticlockwise rotation to the C-Pd-N plane.
Such twisted structures suggesting free spaces accessible to the
reactants have been reported for PdCl2[(R)-binap]32c and
the experimentally observed enantiomer R-product is preferred
thermodynamically (2.6 kcal/mol) over that of the si-face
because of steric requirement between the methyl group of
allylic moiety and the t-butyl group in the lower-right second
quadrant. This is consistent with the experimental results shown
in Table 2 suggesting a small energy difference (1∼2 kcal/mol)
between the two processes giving R- and S-enantiomers.
Experimental Section
General Procedure for γ-Selective Cross-Coupling (Table
1). A 20 mL flask charged with palladium acetate (0.015 mmol, 3
mol %), 1,1′-bis(di-tert-butylphosphino)ferrocene (D-t-BPF) (0.018
mmol), potassium allyltrifluoroborates (1.25 mmol), and K2CO3 (1.5
34
[Pd(PhCN)2(chiraphos)](BF4)2 complexes.
The minimum energy mode of substrate coordination to the
cationic phenylpalladium intermediate was calculated, that is,
the reaction stage directly preceding the stereodetermining
insertion step by DFT calculation at the B3LYP/LANL2DZ level
of theory. Two stable adducts between [Pd(CyPF-t-Bu)(Ph)]+
and 2a located at the C-C double bond from its re-face (28)
or si-face (29) via the SE2′ (open) process without F-chelation
are shown in Scheme 8. Thus, reaction from the re-face yielding
Figure 3. X-Ray structure of [Pd(R,S-CyPF-t-Bu)(4-MeOC6H4)-
(NH3)]+ reported by Shen and Hartwig and possible free space
accessible to reactants.
(33) Shen, Q.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 10028.
(34) Nishikata, T.; Yamamoto, Y.; Gridnev, I. D.; Miyaura, N. Orga-
nometallics 2005, 24, 5025.

Transmetalation and Enantioselection Studies
Organometallics, Vol. 28, No. 1, 2009 159
mmol) was flush with nitrogen. THF (5 mL) and bromoarene
(0.5 mmol) were added successively. After being refluxed for 22 h,
the reaction mixture was treated with 1 N HCl (10 mL) at room
temperature. Flash chromatography on silica gel gave the coupling
product.
(162 MHz, CDCl3) δ 23.42; HRMS m/z: calcd for C33H48F3FeP2Pd
725.1568, found 725.1566.
Pd(D-t-BPF)(Br)(4-MeO2CC6H4) (15). Crystallization from
1
benzene/CH2Cl2/pentane; H NMR (400 MHz, CDCl3) δ 7.82 (d,
J ) 8.3 Hz, 2H), 7.77 (d, J ) 8.3 Hz, 2H), 5.63 (s, 4H), 4.34 (s,
4H), 3.92 (s, 3H), 1.40 (d, J ) 7.8 Hz, 18H), 1.38 (d, J ) 7.3 Hz,
18H); 31P NMR (162 MHz, CDCl3): 18.99; HRMS m/z: calcd for
C34H51FeO2P2Pd 715.1749, found 715.1746; anal. calcd for
C34H51FeO2P2Pd: C, 51.31; H, 6.46; found: 49.27; H, 6.53.
Pd(CyPF-t-Bu)(Br)(4-PhOC6H4)(16).CrystallizationfromCH2Cl2/
pentane; 1H NMR (400 MHz, CDCl3) δ 7.97-7.84 (m, 2H),
7.38-7.24 (m, 4H), 7.15-7.09 (m, 1H), 7.07-6.90 (m, 2H), 5.89
(br s, 1H), 4.89 (s, 1H), 4.52 (s, 1H), 4.26 (s, 5H), 3.21-3.18 (m,
1H), 1.99 (t, J ) 7.1 Hz, 3H), 1.70 (d, J ) 11.7 Hz, 9H), 1.19 (d,
J ) 13.1 Hz, 9H), 2.61-0.86 (m, 22H); 31P NMR (162 MHz,
CDCl3): 74.22 (d, J ) 35.1 Hz), 18.26 (br s); HRMS m/z: calcd
for C44H61FeOP2Pd 829.2582, found 829.2593.
Pd(CyPF-t-Bu)(Br)(C6H5) (17). Crystallization from CH2Cl2/
pentane; 1H NMR (400 MHz, CDCl3) δ 7.50 (br s, 1H), 7.32 (br s,
2H), 6.89-6.84 (m, 2H), 4.89 (br s, 1H), 4.52 (s, 1H), 4.45 (s,
1H), 4.25 (s, 5H), 3.21-3.18 (m, 1H), 1.98 (t, J ) 7.6 Hz, 3H),
1.66 (d, J ) 12.2 Hz, 9H), 1.18 (d, J ) 12.0 Hz, 9H), 2.63-0.86
(m, 22H); 31P NMR (162 MHz, CDCl3) δ 73.51 (d, J ) 36.6 Hz),
18.21 (br s); HRMS m/z: calcd for C38H57FeP2Pd 737.2320, found
737.2328.
Pd(CyPF-t-Bu)(Br)(4-ClC6H4) (18). Crystallization from CH2Cl2/
pentane; 1H NMR (400 MHz, CDCl3) δ 7.11 (d, J ) 8.3 Hz, 2H),
6.89 (d, J ) 7.8 Hz, 2H), 4.88 (br s, 1H), 4.53 (s, 1H), 4.47 (s,
1H), 4.25 (s, 5H), 3.19-3.16 (m, 1H), 1.98 (t, J ) 7.6 Hz, 3H),
1.67 (d, J ) 11.7 Hz, 9H), 1.18 (d, J ) 13.2 Hz, 9H), 2.51-0.86
(m, 22H); 31P NMR (162 MHz, CDCl3) δ 75.03 (d, J ) 33.5 Hz),
18.44 (br s); HRMS m/z: calcd for C38H56ClFeP2Pd 771.1930, found
771.1925.
Pd(CyPF-t-Bu)(Br)(4-CF3C6H4)(19).CrystallizationfromCH2Cl2/
pentane; 1H NMR (400 MHz, CDCl3) δ 7.35 (d, J ) 7.8 Hz, 2H),
7.12 (d, J ) 7.8 Hz, 2H), 4.89 (br s, 1H), 4.54 (s, 1H), 4.48 (s,
1H), 4.26 (s, 5H), 3.19-3.17 (m, 1H), 1.99 (t, J ) 7.4 Hz, 3H),
1.66 (d, J ) 12.7 Hz, 9H), 1.18 (d, J ) 13.2 Hz, 9H), 2.69-0.87
(m, 22H); 31P NMR (162 MHz, CDCl3) δ 77.56 (d, J ) 32.6 Hz),
20.67 (br s); HRMS m/z: calcd for C39H56F3FeP2Pd 805.2194, found
805.2206.
General Procedure for Asymmetric Cross-Coupling (Table
2). A flask charged with potassium (E)-2-butenyltrifluoroborate (2.5
mmol), Pd(OAc)2 (3 mol %), 1-dicyclohexylphosphino-2-di-tert-
butylphosphinoethylferrocene (CyPF-t-Bu) (3.6 mol %), and K2CO3
(3.0 mmol) was flushed with nitrogen. H2O/MeOH (9/1, 5 mL)
and bromoarene (1.0 mmol) were then added. The resulting mixture
was stirred at 80 °C for 22 h. Isolated yields determined by
chromatography on silica gel are shown in Table 2. Enantiomer
excess was determined by a chiral stationary column.
Preparation of Palladium Complexes (Schemes 4 and 5).
Pd2(dba)3 · CHCl3,35 Pd[P(o-tolyl)3]2,36 {Pd[P(o-tolyl)3](Ph)(µ-
Br)}2,36 (D-t-BPF)Pd(Ar)(Br) (Ar ) C6H4-4-OPh (11), C6H5 (12),
C6H4-4-Cl (13), C6H4-4-CF3 (14), C6H4-4-CO2Me (15)),22b (CyPF-
t-Bu)Pd(Ar)(Br) (Ar ) C6H4-4-OPh (16), C6H5 (17), C6H4-4-Cl
(18), C6H4-4-CF3 (19)),37 and [(D-t-BPF)Pd(C6H4-4-CO2Me)](BF4)
(20)22b were prepared according to published methods.
Pd(D-t-BPF)(Br)(4-PhOC6H4) (11). Crystallization from benzene/
CH2Cl2/pentane; 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J ) 15.9
Hz, 1H), 7.54 (d, J ) 8.0 Hz, 1H), 7.43-7.36 (m, 3H), 7.33 (t, J
) 8.0 Hz, 1H), 7.10 (d, J ) 15.9 Hz, 1H), 6.96 (d, J ) 7.1 Hz,
2H), 5.57 (s, 4H), 4.33 (s, 4H), 1.42 (d, J ) 7.1 Hz, 18H), 1.40 (d,
J ) 8.0 Hz, 18H); 31P NMR (162 MHz, CDCl3) δ 23.75; HRMS
m/z: calcd for C38H53FeOP2Pd 749.1956, found 749.1960.
Pd(D-t-BPF)(Br)(C6H5) (12). Crystallization from benzene/
1
CH2Cl2/pentane; H NMR (400 MHz, CDCl3) δ 7.59 (d, J ) 7.8
Hz, 2H), 7.16 (d, J ) 7.4 Hz, 2H), 6.99 (t, J ) 7.1 Hz, 1H), 5.54
(s, 4H), 4.33 (s, 4H), 1.40 (d, J ) 7.4 Hz, 18H), 1.39 (d, J ) 7.8
Hz, 18H); 31P NMR (162 MHz, CDCl3) δ 20.71; HRMS m/z calcd
for C32H49FeP2Pd 657.1694, found 657.1697; anal. calcd for
C33H49FeP2Pd: C, 52.09; H, 6.69; found: 48.73; H, 6.82.
Pd(D-t-BPF)(Br)(4-ClC6H4) (13). Crystallization from benzene/
1
CH2Cl2/pentane; H NMR (400 MHz, CDCl3) δ 7.55 (d, J ) 7.6
Hz, 2H), 7.19 (d, J ) 7.1 Hz, 2H), 5.59 (s, 4H), 4.31 (s, 4H), 1.40
(d, J ) 7.5 Hz, 18H), 1.38 (d, J ) 7.6 Hz, 18H); 31P NMR (162
MHz, CDCl3) δ 23.43; HRMS m/z calcd for C32H48ClFeP2Pd
691.1304, found 691.1307.
Pd(D-t-BPF)(Br)(4-CF3C6H4) (14). Crystallization from benzene/
CH2Cl2/pentane; 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J ) 15.9
Hz, 2H), 7.10 (d, J ) 15.9 Hz, 2H), 5.63 (s, 4H), 4.34 (s, 4H),
1.40 (d, J ) 7.1 Hz, 18H), 1.38 (d, J ) 7.1 Hz, 18H); 31P NMR
Pd(D-t-BPF)(4-MeO2CC6H4)(BF4) (20). AgBF4 (0.91 mmol) in
THF (5 mL) was added to a solution of Pd(D-t-BPF)(Br)(4-
MeO2CC6H4) (0.70 mmol) in CH2Cl2 (35 mL). The suspension was
stirred at room temperature for 1 h. The product was isolated by
filtration. Recrystallization from THF gave brown needles (89%).
1H NMR (400 MHz, CDCl3) δ 7.82 (d, J ) 7.8 Hz, 2H), 7.78 (d,
J ) 7.8 Hz, 2H), 5.41 (s, 4H), 4.30 (s, 4H), 3.92 (s, 3H), 1.39 (t,
J ) 7.3 Hz, 18H), 1.37 (d, J ) 7.4 Hz, 18H); 31P NMR (162 MHz,
CDCl3) δ 21.27; 11B NMR (128 MHz, CDCl3) δ 6.50; HRMS m/z:
calcd for C34H51FeO2P2Pd 715.1749, found 715.1755. The X-ray
structure is shown in Scheme 6.
(35) Ukai, T.; Kawazura, H.; Ishii, Y.; Bonnet, J. J.; Ibers, J. A. J.
Organomet. Chem. 1974, 65, 253.
(36) (a) Paul, F.; Patt, J.; Hartwig, J. F. Organometallics 1995, 14, 3030.
(b) Widenhoefer, R. A.; Zhong, H. A.; Buchwald, S. L. Organometallics
1996, 15, 2745.
(37) Roy, A. H.; Hartwig, J. F. J. Am. Chem. Soc. 2003, 125, 8704.
(38) (a) Lee, C.; Parr, R. G.; Yang, W. Phys. ReV. B 1988, 37, 785. (b)
Becke, A. D. J. Chem. Phys. 1993, 98, 5648. (c) Stephens, P. J.; Devlin,
F. J.; Chabalowski, C. F.; Frisch, M. J. J. Phys. Chem. 1994, 98, 11623.
(39) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K.
N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.;
Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.;
Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li,
X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.;
Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.;
Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels,
A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.;
Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.;
Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz,
P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.;
Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson,
B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03,
revision B.04; Gaussian, Inc.: Pittsburgh, PA, 2003.
Kinetic Measurement of Coupling between Potassium Allyl-
trifluoroborates and p-Substituted Bromoarenes (Scheme 3). To
a solution of Pd(OAc)2 (0.015 mmol), D-t-BPF (0.018 mmol),
potassium (E)-2-butenyltrifluoroborate (0.75 mmol), and K2CO3 (1.5
mmol) in THF (7 mL) was added p-substituted bromoarene (0.5
mmol) (p-PhOC6H4Br, p-MeC6H4Br, PhBr, p-ClC6H4Br, or
p-CF3C6H4Br). The mixture was stirred at 75 °C. The reaction
progress was followed by gas chromatography (GC) analysis of
the coupling product.
Competitive Reactions Using Pd(D-t-BPF)(Ar)(Br) or Pd-
(CyPF-t-Bu)(Ar)(Br) (Schemes 4 and 5). A 20 mL flask was
charged with Pd(D-t-BPF)(Ph)(Br) (0.25 mmol), Pd(D-t-BPF)(Ar)-
(Br) (0.25 mmol Ar ) p-PhOC6H4, p-ClC6H4, p-CF3C6H4), potas-
sium (E)-2-butenyltrifluoroborate (0.75 mmol), and K2CO3 (1.5
mmol) under nitrogen. THF (7 mL) was added, and the resulting

160 Organometallics, Vol. 28, No. 1, 2009
Yamamoto et al.
solution was heated to 75 °C. The relative rate was estimated by
GC analysis of coupling products (a sum of products 6 and 7).
Computational Details. All calculations were performed by
means of the density functional theory method, the hybrid
Becke3LYP functional with a hybrid Becke exchange functional,
and a Lee-Yang-Parr correlation functional as implemented in
Gaussian 03.39,40 The basis sets were described using an effective
core potential (LANL2DZ) for all atoms.41 The structures at the
stationary points were fully optimized at the B3LYP/LANL2DZ
level of theory. Solvent effects on the energy diagram were included
using self-consistent reaction field (SCRF) method using CPCM.42
Tetrahydrofuran (THF) was used as solvent throughout.
Acknowledgment. This work was supported by a Grant-
in-Aid for Scientific Research in Priority Areas (no. 18064001,
Synergy of Elements) and the Global COE Program (No.
B01, Catalysis as the Basis for Innovation in Materials
Science) from the Ministry of Education, Culture, Sports,
Science, and Technology, Japan.
Supporting Information Available: Text describing experi-
mental details, spectral and analytical data of the products, and
X-ray data (PDF). This material is available free of charge via
Internet at http://pubs.acs.org.
OM800832R
(41) (a) Barone, V.; Cossi, M. J. Phys. Chem. A 1998, 102, 1995. (b)
Cossi, M.; Scalmani, G.; Rega, N.; Barone, V. J. Comput. Chem. 2003, 24,
669.
(40) (a) Wadt, W. R.; Hay, P. J. J. Chem. Phys. 1985, 82, 284. (b) Hay,
P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 299.