BINAP versus BINAP(O) in asymmetric intermolecular Mizoroki-Heck reactions: Substantial effects on selectivities

Article abstract of DOI:10.1002/chem.201101695

2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) was employed as chiral ligand in the enantioselective intermolecular Mizoroki-Heck reaction, whereas the use of cognate BINAP(O) (monooxidized BINAP) is unprecedented. The regio- and enantioselectivity of the arylation of representative cyclic alkenes changes dramatically in the presence of hemilabile BINAP(O) instead of BINAP. The arylation of 2,3-dihydrofuran is perfectly regiodivergent (98:2 versus 0:100) and the arylation of cyclopentene is only enantioselective with BINAP(O) [60 versus 10% enantiomeric excess (ee)]. Use of [Pd₂(dba)₃]·dba (dba=dibenzylideneacetone) instead of Pd(OAc)₂ produces as high as 86% ee in the arylation of cyclopentene.

Full text of DOI:10.1002/chem.201101695

DOI: 10.1002/chem.201101695
BINAP versus BINAP(O) in Asymmetric Intermolecular Mizoroki–Heck
Reactions: Substantial Effects on Selectivities**
Thorsten H. Wçste and Martin Oestreich*[a]
Abstract: 2,2’-Bis(diphenylphosphino)-
1,1’-binaphthyl (BINAP) was employed
as chiral ligand in the enantioselective
intermolecular Mizoroki–Heck reac-
tion, whereas the use of cognate
BINAP(O) (monooxidized BINAP) is
unprecedented. The regio- and enantio-
selectivity of the arylation of represen-
tative cyclic alkenes changes dramati-
cally in the presence of hemilabile
BINAP(O) instead of BINAP. The ary-
lation of 2,3-dihydrofuran is perfectly
regiodivergent (98:2 versus 0:100) and
the arylation of cyclopentene is only
enantioselective with BINAP(O) [60
versus 10% enantiomeric excess (ee)].
Use of [Pd
lideneacetone) instead of PdACHTUNGTRENNUNG
(dba)3]·dba (dba=dibenzy-
(OAc)2
produces as high as 86% ee in the ary-
lation of cyclopentene.
Keywords: asymmetric catalysis
·
enantioselectivity · Heck reaction ·
palladium · regioselectivity
Introduction
olution of diastereomeric alkene–palladium(II) hydride in-
termediates has been proposed.[1] Additionally, spectroscop-
ic[4] and quantum-chemical investigations,[5] as well as deute-
rium-labeling studies,[6] have been devoted to understanding
the problem.
Three decades since its discovery,[1] the asymmetric intermo-
lecular Mizoroki–Heck reaction[2] continues to attract atten-
tion, largely as a test reaction for new chiral ligands.[3] The
mechanism of the original transformation (1!2 and/or 3,
Scheme 1) is also of particular interest because the regio-
The ligand appears to govern the regioselectivity to signif-
icant extent.[3] The Hayashi protocol,[1] which uses Pd-
AHCTUNGRTEG(NNUN OAc)2/2,2’-bis(diphenylphosphino)-1,1’-binaphthyl
(BINAP) and several other bidentate phosphine ligands[7,8]
favor double-bond migration (1!3, Scheme 1). Conversely,
predominant formation of 2 (no migration) is observed with
bidentate P,N ligands,[9–11] often combined with [Pd2-
ACHUTNGREN(NUG dba)3]·dba or [PdACHTUNTGERN(NUGN dba)2] (dba=dibenzylideneacetone).
These well-documented experimental observations[3] are in
full accordance with a statement by Hii et al.,[5] who report-
ed that release of the alkene from an intermediate alkene–
palladium(II) hydride complex is faster with P,N (no migra-
tion) than with P,P (migration) chelating ligands.
Scheme 1. Issues of regio- and enantiocontrol in asymmetric intermolecu-
lar Mizoroki–Heck reactions.
In view of the high number of ligands prepared and
tested, we found it remarkable that an almost self-evident
ligand had been disregarded,[12] BINAP monooxide
(BINAP(O)). This omission is particularly intriguing be-
chemical outcome is subtly influenced by several reaction
parameters, which include the palladium source and ligand
used. Moreover, the enantiomeric excess (ee) of the re-
gioisomers formed is profoundly affected by the degree of
double-bond migration in a complicated way and opposite
absolute configurations for 2 and thermodynamically more
stable 3 are possible. A mechanism that involves kinetic res-
cause the reduction of PdACHTNUTRGENNG(U OAc)2 to palladium(0) in the
presence of excess Ph3P yields Ph3PO.[13] Likewise, stoichio-
metric amounts of BINAP(O) [based on PdII!Pd0] are
formed from PdACTHNUTRGNEUNG
(OAc)2 and BINAP,[14] which is why a two-
fold excess of BINAP is often used in asymmetric Mizoro-
ki–Heck reactions with Pd
AHCTUNGTRENNUNG
[a] Dipl.-Chem. T. H. Wçste, Prof. Dr. M. Oestreich
Organisch-Chemisches Institut
phosphine/phosphine oxide ligand[16] BINAP(O) is, there-
fore, a “common contaminant” in these catalyses but it had
never been employed in Mizoroki–Heck reactions as a
chiral ligand alone.[12] We now demonstrate that BINAP(O)
behaves completely differently to BINAP in representative
enantioselective intermolecular Mizoroki–Heck reactions.
Both the regio- and enantioselectivity[17] of the transforma-
tions are markedly influenced.
Westfꢀlische Wilhelms-Universitꢀt Mꢁnster
Corrensstrasse 40
48149 Mꢁnster (Germany)
Fax : (+49)251-83-36501
E-mail: martin.oestreich@uni-muenster.de
[**] BINAP=2,2’-bis(diphenylphosphino)-1,1’-binaphthyl
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201101695.
11914
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 11914 – 11918

FULL PAPER
rationalized by a kinetic resolution of diastereomeric inter-
mediates (except for Table 1, entry 3, columns 7 and 8).[1]
We were, in turn, relieved to see that our results match
those of the Keay[21] and Shibasaki[22] groups.
With the reference data in hand (Table 1, columns 5–8),
we tested BINAP(O) under otherwise identical reaction
conditions (Table 1, columns 9–12). Double the amount of
BINAP(O), based on PdACTHNUTRGNE(NUG OAc)2, was used and we assumed
Results and Discussion
that the BINAP dioxide (BINAP(O)2), generated in situ,
does not act as a ligand. The outcome was unexpected;
alkene migration to give 3 was now the minor pathway (1!
2, Table 1, column 10). With iPr2NEt as the base (Table 1,
entries 1 and 4), the arylation was perfectly regiodivergent
for BINAP(O) (1!2) and BINAP (1!3). The preference
for formation of 2 versus 3 resembles that of P,N ligands;[9,11]
hemilabile BINAP(O) is also a ligand with a stronger and
weaker donor atom (PPh2 and P(O)Ph2).[16] A similar result
had been obtained with 2-diphenylarsino-2’-diphenylphos-
phino-1,1’-binaphthyl (BINAPAs), a BINAP analogue with
a PPh2 group and a poorly donating AsPh2 group (2/3=
62:38).[23] There is also a base effect on regioselectivity. Par-
tial alkene migration is seen with inorganic bases K2CO3
and KOAc (Table 1, entries 2/5 and 3/6). This finding is in-
consistent with the supposed role of a nucleophile in the as-
The preparation of BINAP(O),[18,19] as well as its coordina-
tion chemistry with palladium(0) and palladium(II),[20] are
well established and we successfully followed Gladialiꢃs ex-
pedient cross-coupling route.[19] We then decided to reinves-
tigate the enantioselective arylation of 2,3-dihydrofuran
with PdACHTUNGTRENNUNG 2ACHUTNGTREN(NUGN dba)3]·dba/BINAP
(OAc)2/BINAP[1] (1:2) and [Pd
(1:2)[21] under various conditions for comparison (Table 1,
columns 5–8).
Hayashi et al. had emphasized the crucial role of ace-
tate—introduced with PdACTHNUTRGNE(NUG OAc)2—as a nucleophile in alkene
decomplexation by an associative mechanism.[1,8] Its nucleo-
philicity is dependent on the solvent and base, therefore, we
included polar (THF) and nonpolar media (benzene) and
organic (iPr2NEt) and inorganic bases (K2CO3, KOAc) in
our survey. As expected, alkene migration was observed in
all cases (1!3, Table 1, column 6). A single regioisomer was
formed in both solvents in the presence of iPr2NEt (Table 1,
entries 1 and 4), whereas the slightly diminished regioselec-
tivities when K2CO3 or KOAc were used might be interpret-
ed as a hint that a nucleophile is involved in the alkene re-
lease step[8] (Table 1, entries 2/5 and 3/6). However, the
enantioselectivity was mostly unaffected by both the solvent
and base, and the regioisomers (R)-3 (major) and (R)-2
(minor) had the same absolute configuration. Our data do
not fully agree with previous findings, from which the for-
mation of (R)-3 (major) and (S)-2 (minor) was reported and
sociative alkene decomplexation in Pd
ACHTUNGRTEN(NNUG OAc)2/BINAP-cata-
lyzed reactions.[1]
Dissociation of the alkene–palladium(II) hydride complex
is fast in Pd
(OAc)2/BINAP(O) catalysis,[5] and we believe
AHCTUNGTRENNUNG
that the rate of reductive elimination of the palladium(II)
hydride is the branching point.[24] With fully soluble organic
bases (homogeneous system) reductive elimination is more
facile than with less soluble inorganic bases (heterogeneous
system).[25] That longer lifetime in the latter scenario could
make the hydride complex available for subsequent alkene
insertion. An alternative explanation is provided by Gottu-
mukkala et al. (albeit in a different context).[26] The authors
Table 1. Enantioselective arylation of 2,3-dihydrofuran (1) employing either (R)-BINAP or (R)-BINAP(O).
Palladium
source
X
Base
Solvent
(R)-BINAP
(R)-BINAP(O)
Yield
[%][a]
Ratio
ee of 2
ee of 3
Yield
[%][a]
Ratio
ee of 2
ee of 3
G
[%][c]
[%][c]
G
[%][c]
[%][c]
1
2
3
4
5
6
7
8
9
Pd
Pd
Pd
Pd
Pd
Pd
N
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
I
iPr2NEt
K2CO3
KOAc
iPr2NEt
K2CO3
KOAc
iPr2NEt
iPr2NEt
iPr2NEt
THF
THF
THF
benzene
benzene
benzene
THF
benzene
THF
68
78
75
75
65
78
0:100
16:84
6:94
1:99
2:98
12:88
5:95
1:99
–
66 (R)
64 (R)
72 (R)
64 (R)
66 (R)
84 (R)
60 (R)
66 (R)
0
80
65
56
70
58[d]
79
65
80
62
98:2
92 (R)
70 (R)
24 (R)
88 (R)
68 (R)
20 (R)
92 (R)
94 (R)
–
–
80 (R)
32 (S)
–
–
85:15
75:25
88:12
75:25
88:12
92:8
48 (R)
26 (R)
76 (R)
46 (R)
18 (R)
86 (R)
92 (R)
0
16 (R)
A
E
56[d]
56[d]
58
–
–
–
A
E
95:5
0:100
0:100
[a] Yield refers to analytically pure product isolated after purification by flash chromatography on silica gel. [b] Ratio of regioisomers was determined by
achiral GLC analysis. [c] The ee values were determined by chiral GLC analysis (baseline-separated peaks). [d] Incomplete conversion.
Chem. Eur. J. 2011, 17, 11914 – 11918
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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11915

M. Oestreich and T. H. Wçste
suggested that the amine base acts as a ligand for palladiu-
m(II) after alkene dissociation, which prevents recoordina-
tion of the alkene. Less soluble inorganic bases are, in turn,
present in lower concentration and coordination of the pal-
ladium(II) hydride will be less efficient. As a result, re-es-
tablishment of the alkene–palladium(II) hydride complex is
more likely.
ic bases on these selectivities followed the same trends as
the arylation of 1 (Table 2, entries 2/5 and 3/6). [Pd2-
AHCTUNGRTEGNUN(N dba)3]·dba performed even better (5/6=94:6, 86% ee,
Table 2, entry 8).[27]—Phenyl iodide reacted with similar re-
giocontrol, yet without any asymmetric induction (Table 2,
entry 9).
The mutual dependence of regio- and enantiocontrol
complicates the interpretation of the literature and our data.
The model of an associative mechanism[28] of alkene decom-
plexation from diastereomeric 16e square-planar alkene–
palladium(II) hydride intermediates helps to understand the
degree of alkene migration and the proposed kinetic resolu-
tion.[1,8] Hemilabile BINAP(O) falls into the category of
phosphinooxazoline-type (PHOX) ligands and alkene re-
lease is a facile step.[5,28] Prediction of the absolute stereo-
control is difficult with nonsymmetric chelating ligands and
mechanistic models are scarce.[8,9k] A recent quantum-chemi-
cal study even showed that, in one example, the migratory
insertion of 1 occurs from the least-favored intermediate.[29]
The consistently high ee values obtained with iPr2NEt as
base corroborate, at least, that BINAP(O) acts as a biden-
tate ligand, and the minor deviations in the ee values of 2
and 3 (both R configuration) do not support a kinetic-reso-
lution pathway.
The enantioselectivity under PdACHTNUTRGNEUNG(OAc)2/BINAP(O) cataly-
sis also deserves attention. The ee values are high in the
presence of iPr2NEt (92 and 88% ee, Table 1, entries 1 and
4), but poor in the presence of KOAc (24 and 20% ee,
Table 1, entries 3 and 6). We are aware that the degree of
asymmetric induction in the enantioselectivity-determining
step might be blurred by a late-stage kinetic resolution,[1,5]
but the substantial loss of enantioinduction with excess
KOAc indicates that BINAP(O) might act as a monodentate
chiral ligand in this case. Acetate is likely to replace the
labile P(O)Ph2 group at the palladium(II) center.
A change of the palladium source from PdACHTUNRGTNEUNG(OAc)2 to [Pd2-
ACHTUNGTRENNUNG(dba)3]·dba had little effect on the regio- and enantiocontrol
(Table 1, entries 7 and 8).[27] Reaction with phenyl iodide
produced the thermodynamically more stable regioisomer in
racemic form independent of the chiral ligand (1!3,
Table 1, entry 9).[1]
We next turned to the intermolecular arylation of cyclo-
pentene (4!5/6, Table 2). This asymmetric Mizoroki–Heck
reaction is more challenging than those of heterocycles such
as 1 due to extensive double-bond migration, and only a few
effective catalyses with P,N ligands have been re-
Conclusion
The use of BINAP and BINAP(O) as chiral ligands in the
asymmetric intermolecular Mizoroki–Heck reaction of rep-
resentative cyclic alkenes affords quite different (sometimes
reverse) selectivities. Arylation of 2,3-dihydrofuran (1) is re-
giodivergent (1!3 versus 1!2) and arylation of cyclopen-
tene (4) is only regio- and enantioselective when BINAP(O)
is used (4!5, with a maximum of 86% ee). We are currently
ACHTUNGTRENNUNG
ported.[9a,b,11c,e] Screening with BINAP as the ligand con-
firmed these known problems (Table 2, columns 5–7). Con-
versely, both the regio- and enantioselectivity were again su-
perior when BINAP(O) was used (Table 2, columns 8–10).
An excellent regioisomeric ratio (5/6=94:6) and a decent
enantiomeric excess (60% ee) was obtained in THF with
iPr2NEt as the base (Table 2, entry 1). The effect of inorgan-
Table 2. Enantioselective arylation of cyclopentene (4) employing either (R)-BINAP or (R)-BINAP(O).
Palladium
source
X
Base
Solvent
(R)-BINAP
Ratio
(R)-BINAP(O)
Yield
[%][a]
ee of 5
Yield
[%][a]
Ratio
ee of 5
A
[%][c]
A
[%][c]
1
2
3
4
5
6
7
8
9
Pd
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
[Pd2A(dba)3]·dba
[Pd2A(dba)3]·dba
Pd(OAc)2
G
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
I
iPr2NEt
K2CO3
KOAc
iPr2NEt
K2CO3
KOAc
iPr2NEt
iPr2NEt
iPr2NEt
THF
THF
THF
benzene
benzene
benzene
THF
benzene
THF
52
65
75:25
85:15
83:17
74:26
78:22
68:32
74:26
62:38
78:22
10 (R)
50 (R)
8 (R)
6 (R)
38 (R)
32 (R)
24 (R)
14 (R)
0
50[d]
53[d]
31[d]
75
60
66
69
75
70
94:6
92:8
98:2
90:10
94:6
85:15
92:8
94:6
87:13
60 (R)
18 (R)
26 (R)
80 (R)
34 (R)
14 (R)
84 (R)
86 (R)
0
47[d]
41[d]
69
17[d]
33[d]
24[d]
27
N
E
[a] Yield refers to analytically pure product isolated after purification by flash chromatography on silica gel. [b] Ratio of regioisomers was determined by
achiral GLC analysis. [c] The ee values were determined by chiral GLC analysis (not fully baseline-separated peaks). [d] Incomplete conversion.
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Chem. Eur. J. 2011, 17, 11914 – 11918

BINAP versus BINAP(O)
FULL PAPER
testing BINAP(O) in intramolecular[15a] and desymmetri-
zing[15b] Mizoroki–Heck reactions.
argon. Degassed solvent (1 mL) was added and the reaction mixture was
maintained at ambient temperature for 5 min. A solution of PhOTf
(0.20 mmol, 1.0 equiv), alkene 1 or 4 (1.0 mmol, 5.0 equiv), and iPr2NEt
(0.60 mmol, 3.0 equiv) in the degassed solvent (1 mL) was subsequently
added. The reaction tube was sealed and the reaction mixture was main-
tained at 808C for 24 h. Addition of silica gel to the reaction mixture, fol-
lowed by solvent evaporation under reduced pressure, and purification
by flash column chromatography on silica gel with either cyclohexane/
ethyl acetate or n-pentane as eluent afforded 2 and/or 3 as well as 5–7.
Experimental Section
All reactions were performed in either flame-dried glassware by using
Schlenk techniques under a static pressure of argon or in sealed tubes.
Liquids and solutions were transferred by syringe. Solvents were purified
and dried prior to use following standard procedures: CH2Cl2, MeOH,
and DMF were distilled over calcium hydride and benzene and THF
were distilled over potassium. Solvents were degassed by freeze–pump–
thaw cycles (ꢄ3) or by passing through argon for 15 min. Technical-grade
solvents for extraction and chromatography (cyclohexane, n-pentane,
CH2Cl2, diethyl ether, and ethyl acetate) were distilled prior to use. Ana-
lytical TLC was performed on silica gel SIL G-25 glass plates (Macher-
ey–Nagel). Flash column chromatography was performed on silica gel 60
(40–63 mm, 230–400 mesh, ASTM, Merck) with the indicated solvents.
1H, 13C, 19F, and 31P NMR spectra were recorded in CDCl3 on Bruker
AV300 and Bruker AV400 spectrometers. Chemical shifts (d) are report-
ed in parts per million (ppm) downfield from tetramethylsilane and are
referenced to the residual solvent resonance as the internal standard
(CHCl3: d=7.26 ppm, CDCl3: d=77.16 ppm). Data are reported as fol-
lows: chemical shift, multiplicity (d=doublet, t=triplet, q=quartet, m=
multiplet), coupling constant (Hz), integration. IR spectra were recorded
on a Varian 3100 FTIR spectrophotometer equipped with an attenuated
total reflectance (ATR) unit and are reported (vw=very weak, w=weak,
m=medium, s=strong) in wavenumbers (n˜, cmꢀ1). Achiral gas–liquid
chromatography (GLC) was performed on a Shimadzu GC-17A gas chro-
matograph equipped with a CS-Chromatographie Service SE-54 capillary
column (30 mꢄ0.32 mm, 0.25 mm film thickness) by using the following
program: N2 carrier gas, injection temperature 2508C, detector tempera-
ture 3008C; temperature program: start temperature 408C, heating rate
108Cminꢀ1, end temperature 2808C for 5 min. Chiral GLC was per-
formed on a Shimadzu GC-17A gas chromatograph equipped with a CS-
Chromatographie Service FS-Cyclodex b-I/P capillary column (25 mꢄ
0.32 mm) by using the following program: N2 carrier gas, injection tem-
perature 2508C, detector temperature 3008C; temperature program:
1158C isothermal. Alternatively, chiral GLC was performed on an Agi-
lent Technologies 6890N gas chromatograph equipped with a Supelco
Chiraldex G-TA capillary column (30 mꢄ0.25 mm, 0.12 mm film thick-
ness) by using the following program: N2 carrier gas, injection tempera-
ture 2008C, detector temperature 2208C; temperature program: 708C
isothermal. Optical rotations were measured on a Perkin–Elmer 341 po-
larimeter. Melting points (m.p.) were determined with a Thompson Sci-
entific apparatus and are uncorrected. HRMS, electron-spray-ionization
mass spectrometry (ESI-MS), and electron ionization (EI) mass spec-
trometry were performed by the Analytical Facility at the Organisch-
Chemisches Institut, Westfꢀlische Wilhelms-Universitꢀt Mꢁnster.
(R)-2-Phenyl-2,5-dihydrofuran [(R)-2]: According to GP1 (twofold scale
for full characterization), analytically pure (R)-2 (40 mg, 69%) was ob-
tained from PhOTf (91 mg, 0.40 mmol, 1.0 equiv) and 2,3-dihydrofuran
(1, 0.150 mL, 140 mg, 2.00 mmol, 5.00 equiv) by using PdACTHUNRGTNEUNG(OAc)2 (2.7 mg,
0.012 mmol, 3.0 mol%), (R)-BINAP(O) (15.3 mg, 0.0240 mmol,
6.00 mol%), and iPr2NEt (0.210 mL, 155 mg, 1.20 mmol, 3.00 equiv) in
degassed THF (4 mL). Purification by flash column chromatography on
silica gel (cyclohexane/ethyl acetate=50:1) afforded (R)-2 as a yellow
oil. Rf =0.06 (cyclohexane/ethyl acetate 50:1); GLC (achiral): retention
time (tR)=9.5 min; [a]2D0 =+245.3 (c=0.985 in CHCl3) for 92% ee
([a]D20 =+282 (c=0.92 in CHCl3) for 96% ee[9c]); GLC (FS-Cyclodex b-I/
P, column temperature 1158C isothermal, flow rate 0.5 mLminꢀ1): tR =
23.1 min [(S)-2], tR =23.6 min [(R)-2]; 1H NMR (400 MHz, CDCl3): d=
4.78 (dddd, J=12.8, 4.2, 2.6, 1.6 Hz, 1H), 4.89 (dddd, J=12.8, 6.0, 2.4,
1.6 Hz, 1H), 5.80 (mc, 1H), 5.90 (dddd, J=6.5, 2.4, 2.4, 1.5 Hz, 1H), 6.04
(dddd, J=6.2, 2.4, 1.6, 1.6 Hz, 1H), 7.27–7.38 ppm (m, 5H); 13C NMR
(100 MHz, CDCl3): d=76.0, 88.1, 126.5, 126.8, 128.0, 128.7, 130.1,
142.2 ppm; IR (ATR): n˜ =3030 (vw), 2850 (m), 1602 (vw), 1492 (m), 1453
(m), 1080 (w), 1063 (s), 841 (w), 701 cmꢀ1 (m); HRMS (ESI): m/z: calcd
for C10H10ONa ([M+Na]+): 169.06239; found: 169.06249.
(R)-2-Phenyl-2,3-dihydrofuran [(R)-3]: According to GP1 (twofold scale
for full characterization), analytically pure (R)-3 (40 mg, 68%) was ob-
tained from PhOTf (91 mg, 0.40 mmol, 1.0 equiv) and 2,3-dihydrofuran
(1, 0.150 mL, 140 mg, 2.00 mmol, 5.00 equiv) by using PdACTHUNRGTNEUNG(OAc)2 (2.7 mg,
0.012 mmol, 3.0 mol%), (R)-BINAP (14.9 mg, 0.0240 mmol, 6.00 mol%),
and iPr2NEt (0.210 mL, 155 mg, 1.20 mmol, 3.00 equiv) in degassed THF
(4 mL). Purification by flash column chromatography on silica gel (cyclo-
hexane/ethyl acetate 50:1) afforded (R)-3 as a yellow oil. Rf =0.15 (cyclo-
hexane/ethyl acetate 50:1); GLC (achiral): tR =9.0 min; [a]2D0 =ꢀ28.7 (c=
0.955, CHCl3) for 66% ee ([a]2D0 =ꢀ64.3 (c=1.2, CHCl3) for 93% ee[1a]);
GLC (FS-Cyclodex b-I/P, column temperature 1158C isothermal, flow
rate 0.5 mLminꢀ1): tR =18.3 min [(S)-3], tR =18.7 min [(R)-3]; 1H NMR
(400 MHz, CDCl3): d=2.61 (dddd, J=15.2, 8.4, 2.4, 2.4 Hz, 1H), 3.09
(dddd, J=15.3, 10.7, 2.4, 2.4 Hz, 1H), 4.96 (ddd, J=2.5, 2.5, 2.5 Hz, 1H),
5.52 (dd, J=10.7, 8.4 Hz, 1H), 6.46 (ddd, J=2.5, 2.5, 2.5 Hz, 1H), 7.27–
7.37 ppm (m, 5H); 13C NMR (100 MHz, CDCl3): d=38.0, 82.5, 99.2,
125.7, 127.8, 128.7, 143.2, 145.5 ppm; IR (ATR): n˜ =3031 (vw), 2926 (vw),
2858 (vw), 1620 (m), 1494 (m), 1451 (w), 1135 (m), 1050 (s), 698 cmꢀ1
(m); HRMS (ESI): m/z: calcd for C10H10ONa ([M+Na]+): 169.0624;
found: 169.0622.
(R)-3-Phenylcyclopentene [(R)-5]: According to GP1 (twofold scale for
full characterization), analytically pure (R)-5 (34 mg, 59%) was obtained
from PhOTf (91 mg, 0.40 mmol, 1.0 equiv) and cyclopentene (4,
General procedure for the enantioselective intermolecular Mizoroki–
Heck reaction with Pd
flame-dried sealed tube was successively charged with PdCATHNUGTRNE(NUG OAc)2 (6.0–
(GP1):[1a] Under an argon atmosphere, a
ACHTUNGTRENNUNG(OAc)2 ACHTUNGTRENNUGN
0.180 mL, 136 mg, 2.00 mmol, 5.00 equiv) by using PdACTHNUGTRENUNG(OAc)2 (2.7 mg,
10 mmol, 3.0–5.0 mol%), ligand (12–20 mmol, 6.0–10 mol%), and inorgan-
ic base—if used—(0.60 mmol, 3.0 equiv). The tube was then briefly evac-
uated and backfilled with argon, followed by the addition of a solution of
PhOTf (0.20 mmol, 1.0 equiv), alkene 1 or 4 (1.0 mmol, 5.0 equiv), and
iPr2NEt (0.60 mmol, 3.0 equiv)—if used—in the degassed solvent (2 mL).
The reaction tube was sealed and the reaction mixture was maintained at
808C for 24 h. Addition of silica gel to the reaction mixture, followed by
solvent evaporation under reduced pressure, and purification by flash
column chromatography on silica gel with either cyclohexane/ethyl ace-
tate or n-pentane as eluent afforded 2 and/or 3 as well as 5–7.
0.012 mmol, 3.0 mol%), (R)-BINAP(O) (25.5 mg, 0.0400 mmol,
10.0 mol%), and iPr2NEt (0.210 mL, 155 mg, 1.20 mmol, 3.00 equiv) in
degassed THF (4 mL). Purification by flash column chromatography on
silica gel (n-pentane) afforded (R)-5 as a colorless oil. Rf =0.56 (n-pen-
tane); GLC (achiral): tR =8.9 min; [a]2D0 =+184.7 (c=0.990, CHCl3) for
84% ee ([a]2D0 =+90 (c=1, CHCl3) for 42% ee[30]); GLC (G-TA-Chiral-
dex, column temperature 708C isothermal, flow rate 1.1 mLminꢀ1): tR =
39.6 min [(R)-5], tR =40.6 min [(S)-5]; 1H NMR (400 MHz, CDCl3): d=
1.68–1.78 (m, 1H), 2.35–2.56 (m, 3H), 3.86–3.94 (m, 1H), 5.76–5.80 (m,
1H), 5.92–5.96 (m, 1H), 7.27–7.38 ppm (m, 5H); 13C NMR (100 MHz,
CDCl3): d=32.7, 33.9, 51.5, 126.1, 127.4, 128.5, 132.1, 134.4, 146.7 ppm;
IR (ATR): n˜ =3056 (s), 3027 (s), 2940 (s), 2850 (s), 1601 (s), 1490 (s),
1451 (s), 1355 (m) 1259 (w), 1145 (w), 1076 (s), 1029 (w), 1009 (m), 985
(w), 914 (s), 754 (s), 696 (s), 567 cmꢀ1 (m); HRMS (EI): m/z: calcd for
C11H12 ([M]+): 144.0939; found: 144.0922.
General procedure for the enantioselective intermolecular Mizoroki–
Heck reaction with [Pd
phere, a flame-dried sealed tube was successively charged with [Pd2-
(dba)3]·dba (6.0–10 mmol, 3.0–5.0 mol%) and ligand (12–20 mmol, 6.0–
10 mol%). The tube was then briefly evacuated and backfilled with
(dba)3]·dba (GP2):[11e] Under an argon atmos-
2ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
Chem. Eur. J. 2011, 17, 11914 – 11918
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
11917

M. Oestreich and T. H. Wçste
4-Phenylcyclopentene (6): Depending on the reaction conditions for
GP1, the minor regioisomer 6 was formed in various amounts from the
reaction of PhOTf (45 mg, 0.20 mmol, 1.0 equiv) and cyclopentene (4,
0.090 mL, 68 mg, 1.0 mmol, 5.0 equiv). It was not possible to separate 6
from the major isomer (R)-5 by conventional flash chromatography on
silica gel. GLC (achiral): tR =9.0 min; 1H NMR (300 MHz, CDCl3): d=
2.35–2.56 (m, 2H), 2.83 (m, 2H), 3.47 (tt, J=7.1, 9.0 Hz, 1H), 5.77–5.80
(m, 2H), 7.27–7.38 ppm (m, 5H); 13C NMR (75 MHz, CDCl3): d=41.5,
43.3, 125.9, 127.1, 128.5, 130.0 ppm (the ipso-carbon atom of the phenyl
group was not detected in the 13C NMR spectrum); HRMS (EI): m/z:
calcd for C11H12: 144.0939; found: 144.0910.
[11] Chiral pyridine- and quinoline-based phosphine and phosphinite li-
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S. Kaiser, R. Goddard, A. Pfaltz, Angew. Chem. 2004, 116, 72–76;
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[12] It is important to note that Hayashi et al. had already considered
BINAP(O) to be
a (competing) ligand. However, hemilabile
BINAP(O) was only used as an equimolar additive in the asymmet-
ric intermolecular Mizoroki–Heck reaction with preformed Pd-
AHCTUNGTERG(NUNN BINAP)2. Not unexpectedly, more strongly chelating BINAP out-
Acknowledgements
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We thank the Deutsche Forschungsgemeinschaft (Oe 249/5–1) for finan-
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Received: June 3, 2011
Published online: September 6, 2011
11918
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ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 11914 – 11918