Palladium-catalyzed R(sp3)-Zn/R(sp)-SnBu3 oxidative cross-coupling

Article abstract of DOI:10.1055/s-2007-990863

A novel bond formation through oxidative cross-coupling with desyl chloride as the oxidant has been investigated. The coupling can be carried out under mild conditions. The Csp³-center carbon was involved even in the presence of a β-H, and up to 90% of the desired cross-coupling product was obtained with the secondary Csp³-center substrate. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-990863

PRACTICAL SYNTHETIC PROCEDURES
649
Palladium-Catalyzed R(sp3)–Zn/R(sp)–SnBu3 Oxidative Cross-Coupling
P
d-Catalyze
d
O
i
xidativ
q
e
Cross-Cou
u
pling Reactio
n
ns Jin, Yingsheng Zhao, Haibo Wang, Aiwen Lei*
College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, P. R. of China
Fax +86(27)68754067; E-mail: aiwenlei@whu.edu.cn
Received 18 July 2007; revised 14 August 2007
PSP
No113
Abstract: A novel bond formation through oxidative cross-coupling with desyl chloride as the oxidant has been investigated. The coupling
can be carried out under mild conditions. The Csp3-center carbon was involved even in the presence of a b-H, and up to 90% of the desired
cross-coupling product was obtained with the secondary Csp3-center substrate.
Key words: oxidative cross-coupling, transmetalation, organotin reagents, organozinc reagents, palladium
Procedure 1:
Ph
Pd(dba)2 (5 mol%)
+
Ph
SnBu3
ZnCl
Ph
desyl chloride (3)
Ph
THF
4
2
1
A: 60 °C, 87% (isolated)
B: r.t., 92% (GC)
Procedure 2:
DMA,80 °C
I2
OEt
O
OEt
BrZn
Br
Zn
+
O
6
5
OEt
Pd(dba)2 (5 mol%)
OEt
Ph
SnBu3
+
BrZn
ClZn
THF, r.t.
O
Ph
O
desyl chloride (3)
7
92%
Procedure 3:
Ph SnBu3
Pd(dba)2 (5 mol%)
+
Ph
THF, r.t.
desyl chloride (3)
9
93%
8
Scheme 1
which generally involved ArI or ArBr as the electrophiles.
Recently, by employing electron-rich and/or sterically
Introduction
The transition-metal-catalyzed cross-coupling reaction is hindered ligands in cross-coupling reactions, another
one of the most focused as well as the most fruitful areas breakthrough was achieved by using R1Cl as the electro-
for the construction of carbon–carbon and carbon–het- phile for the above-mentioned cross-couplings.11–24 It was
eroatom bonds.1–3 In general, the reaction involves three proved that the electron-rich and/or sterically hindered
elementary steps: (1) an oxidative addition of R1X (X = I, ligands can facilitate the oxidative addition of ArX and Pd
Br, OTf, etc.) to the metal complexes to form R1MX; (2) species.19,20,25–27
a transmetalation of R1MX with an other organometallic
Compared with above-mentioned achievements, moder-
reagent leading to R1MR2; and (3) a reductive elimination
ate attention was given to the reductive elimination. In
of R1MR2 to form the desired R1–R2 products.4 In the
terms of the influence of electronic property, the use of
1970s, several new cross-coupling reactions were discov-
electron-rich ligands, though accelerating the oxidative
ered by employing different organometallic reagents (in
addition, will inhibit the reductive elimination.28 In fact,
the transmetalation step), such as Kumada reaction (R2Li
there are still many problems and challenges in employing
or R2MgX),5,6 Negishi reaction (R2ZnX, etc.),7,8 Suzuki
Csp3-center as one or both coupling partners.29 The oxida-
reaction [R2B(OH)2],9 and the Stille reaction (R2SnBu3),10
tive addition of Rsp3–X to transition-metal complexes is
slower than others (Rsp–X and Rsp2–X); the fast b-H
SYNTHESIS 2008, No. 4, pp 0649–0654
x
x
.
x
x
.2
0
0
7
elimination of the formed alkyl–metal complexes will
Advanced online publication: 29.10.2007
DOI: 10.1055/s-2007-990863; Art ID: Z17407SS
compete with the cross-coupling;13,29,30 furthermore, ac-
© Georg Thieme Verlag Stuttgart · New York

650
L. Jin et al.
PRACTICAL SYNTHETIC PROCEDURES
cording to Hartwig and Espinet’s report, the reductive therefore transmetalate twice with the organometallic re-
elimination of Csp2–Pd–Csp3 is rather slow.31,32 Due to agents, and finally led to the homocoupling products. This
these problems, it is difficult to promote the oxidative ad- hypothesis encouraged us to further investigate the possi-
dition and the reactive elimination at the same time. It is bility of cross-coupling reaction in this approach, of
noteworthy that Knochel et al. successfully promoted which the key was to find two different organometallic re-
Csp3-invovled cross-coupling by employing the Ni cata- agents, which can selectively transmetalate with RO–Pd
lysts in the presence of olefin ligands or functional groups and Pd–X.
in the substrates.33–37 Not long ago, our research group re-
ported a novel oxidative cross-coupling reactions by using
R2
X
PdX
R1
[Pd]
desyl chloride as the oxidant,38 which seems to be able to
address some of the above problems. Herein, we would
like to report more details regarding this transformation
and the further optimized procedures for the palladium-
catalyzed R(sp3)–Zn/R(sp)–SnBu3 oxidative cross-cou-
pling (Scheme 1).
R2
R2
ROPdX
R1
R1
O
Pd
X
O
O
Scheme 2
After many attempts, it was found that the combination of
Rsp3–Zn and Rsp–Sn in the presence of desyl chloride
was promising. We thus turned our attention to the inves-
tigation of the ligands effects with the results listed in
Table 1. We could see from the data in Table 1 that the
sterically hindered ligands, such as 15,16,17 and 18 only
produced low to moderate amounts of cross-coupling
products, that Ph3P (14) had almost no selectivity as for
the desired cross-coupling, and that the phosphite ligand
19 generated the cross-coupling product in 41% yield.
BINAP (12) and BIPHEP (21) also showed low selectivi-
ties. The reactions using dppf (13), Xantphos (22), and
ligand 20 provided the desired cross-coupling in the yields
of 50%, 41% and 18%, respectively. Surprisingly, the cat-
alyst precursor Pd(dba)2 without extrogenous ligands
showed the best result in this oxidative cross-coupling;
87% yield for the Csp–Csp3 cross-coupling product was
obtained (Table 1, entry 12).
Scope and Limitations
One of our research interests lies in the a-functionaliza-
tion of carbonyl compounds.We have attempted to use a-
halocarbonyl compounds as the electrophiles to couple
with other aryl nucleophiles, such as ArB(OH)2, ArZnX,
etc.; but we unexpectedly observed that the a-halocarbon-
yl compounds could promote the palladium-catalyzed ho-
mocoupling reactions of the nucleophiles.39–41 To
understand the mechanistic pathway of these homocou-
pling reactions, we speculated that the a-halocarbonyl
compounds served as an oxidant. After the oxidative ad-
dition, the C-bound Pd-enolate generated from the oxida-
tive addition of a-halocarbonyl compounds and Pd can
tautomerize into the O-bound Pd-enolate (ROPdX,
Scheme 2), which, containing two leaving groups, could
Table 1 Palladium-Catalyzed Cross-Coupling Oxidized by 3a Using Different Ligands
Ph
Pd(dba)2/L
THF
Ph
Ph
Ph
1
+
2
+
3
+
+
Ph
Ph
4
10
11
Entry
Ligand
Yield (%)a
4
10
11
rac-BINAP
12
1
2
3
4
4.2
50
0.1
trace
19
16
dppf
13
28
Ph3P
14
1.6
27
5.9
t-Bu3P
15
7.5
5.2
2.5
P
5
22
0.6
3
16
Synthesis 2008, No. 4, 649–654 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Pd-Catalyzed Oxidative Cross-Coupling Reactions
651
Table 1 Palladium-Catalyzed Cross-Coupling Oxidized by 3a Using Different Ligands (continued)
Ph
Pd(dba)2/L
THF
Ph
Ph
Ph
1
+
2
+
3
+
+
Ph
Ph
4
10
11
Entry
Ligand
Yield (%)a
4
10
11
O
P
6
46
58
0.8
3.5
9.3
3
O
17
7
36
PtBu2
18
19
tBu
tBu
8
9
41
18
7.4
8.5
O
P
3
H
N
trace
38
28
50
O
PPh2
PPh2
20
MeO
MeO
PPh2
PPh2
10
4.2
0.1
21
11
12
41
87
1.5
0.7
O
PPh2
PPh2
22
none
8.2
a Reaction conditions: reactants 1,2, and 3 (1.5:1.5:1) were mixed in THF in the presence of 5 mol% Pd(dba)2 and 5 mol% bidentated ligand or
10 mol% monophosphine ligand in 60 °C; the yield was detected in 5 h by GC using naphthalene as the internal standard.
Under the guide of the newly developed protocol for Pd- pleased to conclude that the Pd(dba)2 system could work
catalyzed oxidative cross-coupling, we investigated the very well with such substrates (Table 2).
substrate scope under the following reaction conditions: 5
mol% of Pd(dba)2 and 2.0 equivalents of alkylzinc re-
agents in THF at 60 °C (Table 2). It was found that be-
sides the 87% yield of the cross-coupling product 4, the
reaction of alkynylstannane 32 with alkylzinc reagent 2
generated the cross-coupling product 30 in a high yield of
Further experiments showed that the transformation can
be carried out at room temperature. Alkynylstannane 1,
when treated with alkylzinc reagent 2, yielded the cross-
coupling product in 92% yield (Scheme 1, Procedure 1).
Using the alkylzinc reagent 6, which contains an ester
functional group, the desired cross-coupling product was
80% (Table 2, entry 9). After examining the reactions of
produced in 92% yield in the presence of Pd(dba)2
other alkylzinc reagents containing b-hydrogen, we were
Synthesis 2008, No. 4, 649–654 © Thieme Stuttgart · New York

652
L. Jin et al.
PRACTICAL SYNTHETIC PROCEDURES
Table 2 Palladium-Catalyzed Oxidative Cross-Couplinga
mediate V. The reductive elimination of V yields the de-
sired cross-coupling product. The transmetalations of
RO–Pd–Cl with a Csp3–Zn and Csp–Sn reagents are note-
worthy, for alkylzinc reagents could transmetalate with ei-
ther RO–Pd or Pd–Cl bonds. To achieve high selectivity
for the Csp–Csp3 cross-coupling product, the alkylzinc re-
agents should only transmetalate one of RO–Pd or Pd–Cl
bonds. In kinetic experimentations, we observed the for-
mation of enolate IV with in situ IR monitoring (ReactIR
4000), and found that this rate equaled the decreasing rate
of desyl chloride 3. This result clearly indicated that the
alkylzinc reagents could selectively transmetalate with
RO–Pd.
Entry Rsp–SnBu3
Product
Yield
(%)a
Ph
Ph
SnBu3
1
87
Ph
4
1
Ph
n-C8H17
n-C12H25
Ph
2
3
1
1
91
94
23
Ph
24
4
1
1
93
Ph
In conclusion, we have explored a novel approach to the
cross-coupling reactions. In the presence of desyl chloride
as the oxidant, alkylzinc reagents and alkynylstannanes,
two different nucleophiles can be coupled together in high
yield and selectivities. The alkylzinc reagents can contain
a b-H, and the secondary alkylzinc reagent can be smooth-
ly coupled in high yield at room temperature.
25
Ph
n-Bu
5
6
7
76
77
95
26
n-C5H11
n-C5H11
32
SnBu3
n-C8H17
27
n-C5H11
n-C12H25
32
28
Ph
8
9
32
32
94
n-C5H11
Procedures
29
Three typical procedures are described for the oxidative cross-cou-
pling transformation.
Ph
80
67
n-C5H11
All reactions and manipulations were performed in a N2-filled
glove-box or using standard Schlenk techniques; column chroma-
tography was performed using EM silica gel 60 (200–300 mesh). 1H
NMR and 13C NMR spectra were recorded on Mercury 300 spec-
trometer. GC-MS spectra were recorded on a Varian GC-MS 3900-
30
n-C5H11
n-Bu
10 32
31
1
a Reaction conditions: reactants Csp3–Zn, Csp–Sn and desyl chloride
(2:1.2:1) were mixed in THF in the presence of 5 mol% Pd(dba)2 in
60 °C; isolated yield.
2100T spectrometer. All H NMR experiments were reported in
parts per million (ppm) downfield of TMS. All 13C NMR spectra
were obtained with 1H decoupling and reported in ppm. Gas chro-
matographic analyses were preformed on Varian GC 2000 gas chro-
matography instrument with an FID detector and naphthalene was
employed as internal standard.
(Scheme 1, Procedure 2). With a secondary alkylzinc re-
agent 8, the desired Csp–Csp3 product was obtained in a
noticeable 93% yield (Scheme 1, Procedure 3).
All common reagents were prepared in the laboratory or obtained
from commercial suppliers and were purified following standard
procedure. Organotins were prepared by reaction of the correspond-
ing Grignard reagents with Bu3SnCl, and purified by distillation un-
der reduce pressure.42 Pd(dba)2 was prepared following general
methods.43 THF was dried and distilled from sodium/benzophenone
ketyl under N2. All alkylzincs, except the (4-ethoxy-4-oxobu-
tyl)zinc(II) bromide (6), were prepared from RMgX and anhyd
ZnCl2.44 Anhyd ZnCl2 was obtained by refluxing the commercial
ZnCl2 with SOCl2 for one or two days.
The proposed mechanism is shown in Scheme 3. The ox-
idative addition of desyl chloride 3 to the Pd(0)-species
generates C-bound Pd-enolate I, which then tautomerizes
to O-bound Pd-enolate II. The intermediate II contains a
chloride anion and an enolate anion, which can serve as
leaving groups. Thus, we speculated that the enolate II
(RO–Pd–Cl) could transmetalate twice respectively with
alkylzinc and tin reagents, which can generate the inter-
Cl
Cl
Pd(II)
Ph
Ph
Ph
Ph
Ph
Ph
O
3
O
OPd(II)Cl
I
II
Pd(0)
ZnCl
2
Ph
Ph
Ph
Ph
Ph
Pd
Ph
Pd Cl
OZnCl
Ph
IV
Ph
V
III
ClSnBu3
Ph
SnBu3
Scheme 3
Synthesis 2008, No. 4, 649–654 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Pd-Catalyzed Oxidative Cross-Coupling Reactions
653
Palladium-Catalyzed Oxidative Coupling; 1-(4-Methyl-4-phe-
nylpent-1-ynyl)benzene (4); Procedure 1
nyl)stannane (1; 460 mg; 1.2 mmol), desyl chloride (3; 230 mg, 1.0
mmol), and Pd(dba)2 (27.5 mg, 5 mol% Pd) were added and the
mixture was stirred for 5 h at r.t. After that, aq 1 M KF (50 mL) was
added to the flask and the mixture was stirred for 2 h. The resulting
mixture was extracted with Et2O (3 × 50 mL). The organic phase
was combined and dried (Na2SO4), filtered, and concentrated by ro-
tary evaporation. The GC yield of the product 9 was estimated to be
93% (naphthalene as the internal standard). The product was puri-
fied by column chromatography [eluent: petroleum ether (bp 30–60
°C)]; yield: 154.8 mg (84%).
1H NMR (300 MHz, CDCl3): d = 7.35–7.27 (m, 2 H), 7.24–7.17 (m,
3 H), 2.60–2.40 (m, 1 H), 1.90–1.75 (m, 2 H), 1.74–1.60 (m, 2 H),
1.58–1.38 (m, 3 H), 1.36–1.21 (m, 3 H).
13C NMR (75 MHz, CDCl3): d = 131.8, 128.4, 127.6, 94.7, 80.4,
32.9, 29.9, 26.2, 25.1.
Conditions A: A dried 10 mL Schlenk flask equipped with a rubber
septum and a magnetic stirring bar was charged with anhyd ZnCl2
(312.8 mg, 2.3 mmol) and THF (2 mL). The solution was cooled in
an ice bath at 0 °C while (2-methyl-2-phenylpropyl)magnesium
chloride (3.0 mL, 0.5 M, 1.5 mmol) was added dropwise over 10
min. The resulting mixture was stirred for 2 h at r.t. To this zinc re-
agent solution were added tributyl(phenylethynyl)stannane (1;
470.0 mg, 1.2 mmol), desyl chloride (3; 230.7 mg, 1.0 mmol), and
Pd(dba)2 (28.7 mg, 5 mol% Pd). The mixture was stirred at 60 °C
for 2 h and then poured into aq 1 M KF (50 mL). The aqueous layer
was extracted with Et2O (100 mL), and the organic layer was
washed repeatedly with aq KF until there was no precipitation be-
tween the two phases. The organic extracts was dried (Na2SO4), fil-
tered, and concentrated by rotary evaporation. After flash column
chromatography, product 4 was obtained as a light yellow oil (203.6
mg, 87%).
Acknowledgment
1H NMR (300 MHz, CDCl3): d = 7.41–7.38 (m, 2 H), 7.30–7.23 (m,
4 H), 7.20–7.16 (m, 4 H), 2.62 (s, 2 H), 1.42 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 147.7, 130.7, 127.3, 126.7, 125.1,
124.9, 123.2, 87.4, 81.7, 37.2, 33.9, 27.4.
This work was supported by National Natural Science Foundation
of China (20502020) and the start-up fund from Wuhan University,
Wuhan, P. R. of China. We thank Prof. Xinquan Hu for helpful dis-
cussions.
MS (EI): m/z = 234.0, 119.0, 91.1, 77.2, 63.0.
HRMS (EI): m/z calcd for C18H18: 234.1409; found: 234.1380.
References
Conditions B: The procedure was the same as given for conditions
A except that the reaction was carried out at r.t. with 1.5 equiv alkyl-
zinc reagent and the yield was 92% (GC).
(1) Crabtree, R. H. The Organometallic Chemistry of the
Transition Metals, 3rd ed.; Wiley: New York, 2001.
(2) Negishi, E.-i.; de Meijere, A. Handbook of
Organopalladium Chemistry for Organic Synthesis; Wiley-
Interscience: New York, 2002.
Palladium-Catalyzed Oxidative Coupling; Ethyl 6-Phenyl-
hex-5-ynoate (7); Procedure 2
(3) Tsuji, J. Transition Metal Reagents and Catalysts:
Innovations in Organic Synthesis; Wiley: Chichester, 2000.
(4) de Meijere, A.; Diederich, F. Metal-Catalyzed Cross-
Coupling Reactions, 2nd ed.; Wiley-VCH: Weinheim, 2004.
(5) Tamao, K.; Kiso, Y.; Sumitani, K.; Kumada, M. J. Am.
Chem. Soc. 1972, 94, 9268.
(6) Tamao, K.; Sumitani, K.; Kumada, M. J. Am. Chem. Soc.
1972, 94, 4374.
(7) Negishi, E.; Okukado, N.; King, A. O.; Van Horn, D. E.;
Spiegel, B. I. J. Am. Chem. Soc. 1978, 100, 2254.
(8) King, A. O.; Okukado, N.; Negishi, E. J. Chem. Soc., Chem.
Commun. 1977, 683.
A dried 10 mL Schlenk flask equipped with a rubber septum and a
magnetic stirring bar was evacuated and refilled with N2 three
times. The flask was charged with Zn dust (126.7 mg, 1.95 mmol)
and I2 (22.5 mg, 0.089 mmol). Anhyd DMA (5 mL) was added to
the flask via a syringe. The mixture was stirred at r.t. for a few min
until the color of I2 had disappeared. Then ethyl 4-bromopentanoate
(5; 240.0 mg, 1.23 mmol) was added via a syringe and the mixture
was stirred for 3 h at 80 °C to produce a solution of the zinc reagent
and a suspension of excess zinc dust. The solution was allowed to
cool to r.t. and tributyl(phenylethynyl)stannane (1; 235.0 mg, 0.60
mmol), desyl chloride (3; 115.8 mg, 0.50 mmol), Pd(dba)2 (14.3
mg, 5 mol% Pd), and THF (2 mL) were added. The mixture was
then stirred for 5 h at r.t. The resulting mixture was diluted with
Et2O (100 mL) and washed with aq 1 M KF repeatedly until there
was no precipitation between the two phases. The organic phase
was combined and dried (Na2SO4), filtered, and concentrated by ro-
(9) Miyaura, N.; Suzuki, A. J. Chem. Soc., Chem. Commun.
1979, 866.
(10) Stille, J. K. Pure Appl. Chem. 1985, 57, 1771.
(11) Kataoka, N.; Shelby, Q.; Stambuli, J. P.; Hartwig, J. F. J.
Org. Chem. 2002, 67, 5553.
(12) Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc.
1998, 120, 9722.
(13) Cardenas, D. J. Angew. Chem. Int. Ed. 2003, 42, 384.
(14) Altenhoff, G.; Goddard, R.; Lehmann, C. W.; Glorius, F.
Angew. Chem. Int. Ed. 2003, 42, 3690.
1
tary evaporation. A 92% yield was determined by H NMR spec-
troscopy (dibromomethane as the internal standard).45
1H NMR (300 MHz, CDCl3): d = 7.40–7.38 (m, 2 H), 7.28–7.26 (m,
3 H), 4.14 (q, J = 10.6 Hz, 2 H), 2.52–2.46 (m, 4 H), 1.98–1.88 (m,
2 H), 1.26 (t, J = 6.9 Hz, 3 H).
(15) Navarro, O.; Kelly, R. A. III; Nolan, S. P. J. Am. Chem. Soc.
2003, 125, 16194.
MS (EI): m/z = 216.0, 188.0, 174.0, 143.2, 128.0.
(16) Eckhardt, M.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 13642.
(17) Milne, J. E.; Buchwald, S. L. J. Am. Chem. Soc. 2004, 126,
13028.
(18) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998, 120,
7369.
(19) Littke, A. F.; Fu, G. C. J. Org. Chem. 1999, 64, 10.
(20) Littke, A. F.; Fu, G. C. Angew. Chem. Int. Ed. 1999, 38,
2411.
(21) Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 2719.
(22) Hadei, N.; Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G.
Org. Lett. 2005, 7, 3805.
Palladium-Catalyzed Oxidative Coupling; 1-(2-Cyclohexyl-
ethynyl)benzene (9); Procedure 3
A dried 100 mL Schlenk flask equipped with a magnetic stirring bar
was charged with anhyd ZnCl2 (1.36 g, 10 mmol). The flask was
evacuated and heated with a heat gun for 10 min, flushed three times
with N2, and then allowed to cool to r.t. THF (20 mL) was added to
the flask. Then the mixture was cooled to –25 °C and cyclohexyl-
magnesium chloride (5.9 mL, 0.85 M, 5.0 mmol) was added drop-
wise via a syringe at –25 °C. A white precipitate was formed
immediately. The mixture was kept at –25 °C for an additional 1 h
before immersing in an ice-water bath. Afterwards the temperature
was allowed to slowly increase to r.t. After 3 h, tributyl(phenylethy-
Synthesis 2008, No. 4, 649–654 © Thieme Stuttgart · New York

654
L. Jin et al.
PRACTICAL SYNTHETIC PROCEDURES
(23) Hadei, N.; Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G.
J. Org. Chem. 2005, 70, 8503.
(24) Campos, K. R.; Klapars, A.; Waldman, J. H.; Dormer, P. G.;
Chen, C.-y. J. Am. Chem. Soc. 2006, 128, 3538.
(25) Barrios-Landeros, F.; Hartwig, J. F. J. Am. Chem. Soc. 2005,
127, 6944.
(35) Giovannini, R.; Stuedemann, T.; Devasagayaraj, A.; Dussin,
G.; Knochel, P. J. Org. Chem. 1999, 64, 3544.
(36) Giovannini, R.; Knochel, P. J. Am. Chem. Soc. 1998, 120,
11186.
(37) Giovannini, R.; Studemann, T.; Dussin, G.; Knochel, P.
Angew. Chem. Int. Ed. 1998, 37, 2387.
(26) Hills, I. D.; Netherton, M. R.; Fu, G. C. Angew. Chem. Int.
Ed. 2003, 42, 5749.
(27) Littke, A. F.; Fu, G. C. Angew. Chem. Int. Ed. 1999, 37,
(38) Zhao, Y.; Wang, H.; Hou, X.; Hu, Y.; Lei, A.; Zhang, H.;
Zhu, L. J. Am. Chem. Soc. 2006, 128, 15048.
(39) Lei, A.; Srivastava, M.; Zhang, X. J. Org. Chem. 2002, 67,
1969.
3387.
(28) Collman, J. P.; Hegedus, L. S. Principles and Applications
of Organotransition Metal Chemistry, 2nd ed.; University
Science Books: Mill Valley, CA, 1987.
(29) Luh, T.-Y.; Leung, M.-k.; Wong, K.-T. Chem. Rev. 2000,
100, 3187.
(30) Cardenas, D. J. Angew. Chem. Int. Ed. 1999, 38, 3018.
(31) Culkin, D. A.; Hartwig, J. F. Organometallics 2004, 23,
3398.
(40) Lei, A.; Zhang, X. Org. Lett. 2002, 4, 2285.
(41) Lei, A.; Zhang, X. Tetrahedron Lett. 2002, 43, 2525.
(42) Moloney, M. G.; Pinhey, J. T.; Roche, E. G. J. Chem. Soc.,
Perkin Trans. 1 1989, 333.
(43) Djakovitch, L.; Wagner, M.; Hartung, C. G.; Beller, M.;
Koehler, K. J. Mol. Catal. A: Chem. 2004, 219, 121.
(44) Knochel, P.; Jones, P. Organozinc Reagents: A Practical
Approach; Oxford University Press: Oxford, 1999.
(45) The desired cross-coupling product was mixed with 1,2-
diphenylethanone, which was formed from the Zn-enolate
IV. Efforts to completely separate the two compounds were
unsuccessful.
(32) Casares, J. A.; Espinet, P.; Fuentes, B.; Salas, G. J. Am.
Chem. Soc. 2007, 129, 3508.
(33) Devasagayaraj, A.; Stuedemann, T.; Knochel, P. Angew.
Chem., Int. Ed. Engl. 1996, 34, 2723.
(34) Jensen, A. E.; Knochel, P. J. Org. Chem. 2002, 67, 79.
Synthesis 2008, No. 4, 649–654 © Thieme Stuttgart · New York