Efficient palladium-catalysed carbonylative and Suzuki-Miyaura cross-coupling reactions with bis(di-tert-butylphosphino)-o-xylene

Article abstract of DOI:10.1016/j.tetlet.2009.02.200

The use of the ligand bis(di-tert-butylphosphino)-o-xylene (dtbpx) in palladium-catalysed carbonylative and Suzuki-Miyaura cross-coupling reactions is described. Aryl and vinyl halides readily entered into the carbonylative catalytic cycle affording carboxylic acids, amides as well as primary, secondary and tertiary esters, respectively, in good yields. Aryl iodides, bromides and chlorides gave high yields of biphenyl products upon reaction with both activated and unactivated boronic acids.

Full text of DOI:10.1016/j.tetlet.2009.02.200

Tetrahedron Letters 50 (2009) 2342–2346
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Efficient palladium-catalysed carbonylative and Suzuki–Miyaura cross-coupling
reactions with bis(di-tert-butylphosphino)-o-xylene
a,*
a
a
b
James McNulty , Jerald J. Nair , Marcin Sliwinski , Al J. Robertson
a
Department of Chemistry, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4M1
Cytec Canada Inc., PO Box 240, Niagara Falls, Ontario, Canada L2E 6T4
b
a r t i c l e i n f o
a b s t r a c t
Article history:
The use of the ligand bis(di-tert-butylphosphino)-o-xylene (dtbpx) in palladium-catalysed carbonylative
and Suzuki–Miyaura cross-coupling reactions is described. Aryl and vinyl halides readily entered into the
carbonylative catalytic cycle affording carboxylic acids, amides as well as primary, secondary and tertiary
esters, respectively, in good yields. Aryl iodides, bromides and chlorides gave high yields of biphenyl
products upon reaction with both activated and unactivated boronic acids.
Received 17 February 2009
Revised 25 February 2009
Accepted 26 February 2009
Available online 4 March 2009
Ó 2009 Elsevier Ltd. All rights reserved.
We have been involved in the development of hindered phos-
phine ligands and active catalytic systems for palladium-catalysed
cross-coupling reactions over the last few years. In addition, the
palladium-catalysed methoxycarbonylation of ethene, long chain
alkenes (linear selectivity >95%), vinyl acetate (branched selectiv-
1
6
ity >77%) and unsaturated esters (to give
a
,x
-diesters). Further-
7
use of sustainable media such as phosphonium salt ionic liquids
more, it is active in the rhodium-catalysed carbonylation of
methanol giving acetic acid, a variant of the Monsanto process that
involves oxidative addition to iodomethane or equivalent. The
most important application developed so far with ligand 1 is in
the palladium-catalysed methoxycarbonylation of ethene to form
methyl propanoate, with high turnover and selectivity (99.98%).8
This forms part of a two-stage route to methyl methacrylate, a pro-
(
PSILs) for these and other processes has been shown by us to be
of synthetic and mechanistic significance employing these cata-
2
lytic systems. A large number of both mono- and bidentate
phosphine ligands have been successfully used in the palladium-
catalysed formation of C–N, C–O and C–C bonds.3 In particular,
3
hindered monodentate phosphines such as biaryl 2 and P(tBu) 3,
9
have been shown to be highly effective in the promotion of a wide
cess currently commercialised by Lucite. Evidence has been pro-
range of C–C and C–heteroatom bond forming reactions.3
a–q
vided that the highly unusual chemoselectivity favouring
methoxycarbonylation using palladium complexes of 1 may actu-
ally involve a monodentate-doubly ortho-metalated palladium
8
species. It has also been shown that formation of methyl propan-
P(Cy)2
oate employing dtbpx 1 occurs via a catalytic mechanism involving
P
P
a Pd(II) hydride species rather than the usual methoxycarbonyl cy-
1
0
cle. The use of dtbpx 1 in the carbonylation of chloroaromatic
1
1
compounds has been shown to be of limited scope. No other re-
ports exist on the use of complexes of ligand 1 in the hydroxy-, alk-
oxy- or aminocarbonylation through oxidative addition to aryl and
vinyl halides. All of the evidence would seem to indicate that pal-
ladium complexes of ligand 1 would be expected to be useful in
dtbpx 1
2
As a continuation of our work, we were interested in bulky
ortho-xylylphosphines such as the commercially available bis(di-
tert-butylphosphino)-o-xylene (dtbpx) ligand 1. Bulky, electron-
donating phosphines generally favour the oxidative addition step
in reaction with aryl or vinyl halides, although it has also been
shown that ligand exchange may be hindered using bidentate li-
gands such as dtbpx. The reductive elimination step is promoted
by ligands that are either electron-poor, bulky, or that possess a
wide bite angle. Ligand 1 has been shown to be effective in the
4
O
Nu
X
4
e
Pd(OAc) , dtbpx, Cs CO , CO (40 psi),
2
2
3
R
R
Nucleophile, DMF, 80 oC, 6-8 hr
5
X = I, Br, Cl, OTf
Nu = OH, OR', NR'2
*
Corresponding author. Tel.: +1 905 525 9140x27393; fax: +1 905 522 2509.
E-mail address: jmcnult@mcmaster.ca (J. McNulty).
Scheme 1. General reaction for carbonylative cross coupling using dtbpx.
0
040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.02.200

J. McNulty et al. / Tetrahedron Letters 50 (2009) 2342–2346
2343
Table 1
1
4
Carbonylation using dtbpx as ligand
Pd(OAc) , dtbpx, Cs CO , CO (40 psi)
2
2
3
R-X
R-CO-Nu
Nu, DMF, 80 oC, 6-8 hr
4
5
Entry
1
R-X
Nu
Product 5
Isolated yield of 2 (%)
95
I
CO Bu
2
BuOH
Br
Cl
OTf
CO Bu
2
2
3
4
5
6
BuOH
BuOH
BuOH
BuOH
BuOH
84
27
20
97
95
CO Bu
2
CO Bu
2
I
CO Bu
2
O N
O N
2
2
Br
CO Bu
2
O N
O N
2
2
Br
CO Bu
2
7
8
9
BuOH
BuOH
80
81
NO2
NO2
Br
CO Bu
2
(E)/(Z)=90/10
(E)/(Z)>99
Br
CO iPr
2
i-PrOH
i-PrOH
72
65
O N
O N
2
2
Br
CO iPr
2
1
0
NO2
NO2
Br
CO iPr
2
1
1
1
2
i-PrOH
t-BuOH
64
42
(
E)/(Z)=90/10
(E)/(Z)>99
CO tBu
Br
2
O N
O N
2
2
Br
CO tBu
2
1
1
1
3
4
5
t-BuOH
t-BuOH
39
36
NO2
NO2
Br
CO tBu
2
(E)/(Z)=90/10
(E)/(Z)>99
Br
CO H
2
H
2
O
77
(continued on next page)

2
344
J. McNulty et al. / Tetrahedron Letters 50 (2009) 2342–2346
Table 1 (continued)
Entry
R-X
Nu
Product 5
Isolated yield of 2 (%)
84
Br
CO H
2
16
17
18
19
20
H
2
H
2
H
2
O
O
O
O N
O N
2
2
Br
CO H
2
78
76
83
86
NO2
NO2
Br
CO H
2
(
E)/(Z)=90/10
(E)/(Z)>99/1
CONEt2
Br
NHEt
2
2
Br
CONEt2
NHEt
O N
O N
2
2
general cross-coupling reactions proceeding via oxidative addition.
Nonetheless, a recent publication reported palladium complexes of
ligand 1 to be poor to moderately successful in C–N bond forma-
tion (up to 40% conversion) and Suzuki–Miyaura cross coupling
example, yields on the alkoxycarbonylation of 2-nitrobromoben-
zene decreased from n-BuOH (80%), i-PrOH (65%) to t-BuOH
(39%), (Table 1 entries 7, 10 and 13). In general, t-butyl esters were
obtained in the 36–42% yield range using this hindered nucleophile
(Table 1, entries 12–14).
1
2
(
up to 60% conversion). These results appeared to be unusual.
The high reactivity of monodentate phosphines such as 2 in many
Both aryl and vinyl halides entered successfully into the
hydroxycarbonylation cycle giving carboxylic acids in 76–84% iso-
lated yield, with electronic and steric effects apparently minimal
(entries 15–18). The use of a secondary amine as incoming nucle-
ophile was also demonstrated in the conversion of aryl bromide
substrates to the corresponding diethylamides (Table 1, entries
19 and 20).
3
cross-coupling reactions coupled with the involvement of mono-
8
dentate Pd-complexes being formed of 1, the high reactivity of 1
in carbonylation-type reactions, the demonstrated potential of li-
gand 1 in oxidative addition reactions11 and the bulky electron-
rich nature of the ligand all indicate that a highly active catalytic
species should be accessible under the right conditions. Herein
we report on our findings that palladium complexes of 1 are indeed
useful general catalysts in both carbonylation and Suzuki–Miyaura
palladium cross-coupling reactions.
The general reaction for carbonylation with Pd(OAc) /dtbpx is
2
outlined in Scheme 1. The initial carbonylation screen proved
immediately successful. A catalyst system was developed (2.5%
A similar efficient catalytic system was also readily developed
for Suzuki–Miyaura coupling, employing ligand 1, Pd(OAc) and
2
the relatively mild conditions which are outlined in Table 2. All
reactions reported in Table 2 were conducted under the conditions
shown without further individual optimisation. Under these condi-
tions aryl iodides reacted readily with 4-acetylphenylboronic acid
affording the corresponding biphenyls in excellent yields (entries
1–3). Unactivated and electron-rich aryl bromides gave high yields
of biphenyl products upon reaction with both electron-rich and
electron-deficient boronic acids (Table 2, entries 4–9), while elec-
tron-deficient aryl bromides were efficiently converted to biphenyl
adducts (Table 2, entries 10 and 11). The ortho-steric effects on the
outcome of the reaction were again observed to be minimal (Table
2, entries 12 and 13). The coupling of 4-chloroacetophenone with
4-methoxyphenyl boronic acid (in toluene at 90 °C) gave the
biphenyl product in 80% yield, whereas the less activated 4-chloro-
toluene gave only 35% of biphenyl under these conditions. Entries
14 and 15 represent the first demonstration of dtbpx-mediated Su-
zuki–Miyaura coupling of aryl chlorides.
2 2 3
Pd(OAc) , 5% dtbpx, 1.5 equiv Cs CO , 2 equiv butanol, CO at
4
0 psi, DMF at 80 °C) and screened using 4-iodotoluene as sub-
strate. This gave butyl 4-methylbenzoate in 95% isolated yield after
only 6–8 h. The scope of the reaction was then expanded to include
aryl bromides (Table 1, entries 2 and 6). Under these conditions
aryl chlorides and triflates suffered from poor conversion to butyl
esters (Table 1, entries 3 and 4). This is in accordance with the pre-
1
1
vious report which demonstrated that, amongst a range of aryl
chlorides, only the more electrophilically activated substrates
(
such as 4-chloroacetophenone) could be successfully carbonylat-
ed, and then only with alcohols of low nucleophilicity, such as
3
2
,2,2-trifluoroethanol. Although a few reports1 exist on the use
of palladium complexes of 1,4-bis(diphenylphosphino)butane
dppb), 1,4-bis(diphenylphosphino)ferrocene (dppf) and 1,4-
(
Taken together with the efficient conversion of aryl iodides and
bromides, these results clearly demonstrate that the scope of the
Suzuki–Miyaura cross-coupling reaction with dtbpx 1 is much
wider than the single previously reported example using this li-
bis(dicyclohexylphosphino)ferrocene for the methoxycarbonyla-
tion of aryl and heteroaryl chlorides, these substrates remain a
challenge due largely to the presence of the good
p-acceptor CO
1
2
12
which reduces the tendency towards oxidative addition at the me-
tal centre and also promotes formation of palladium clusters.
Returning to the aryl and vinyl bromides, ortho-steric effects were
observed to be minimal (Table 1, entry 7), and vinyl halides (e.g., b-
gand. We note that in the report of Wills et al., bidentate 1,3-
and 1,4-bis(di-tert-butylphosphino)-substituted propane and bu-
tane ligands, respectively, were shown to be more adept than
dtbpx 1 at this transformation. In contrast, monodentate ligands
3
d–f
bromostyrene) gave the corresponding
a
,b-unsaturated butyl ester
as described by Fu et al.,
2 3 3
utilising Pd (dba) with P(t-Bu)
(
Table 1, entry 8) with complete (E)-geometry in 81% isolated yield.
(1:2), and monophosphine-based biaryl ligands described by Buch-
3
o,q
Steric effects were seen to be significant on the part of the alcohol
with yields decreasing as the bulk of the alcohol increases. For
wald
are perhaps the benchmark systems for difficult Suzuki–
Miyaura cross-couplings, including less-activated aryl chlorides.

J. McNulty et al. / Tetrahedron Letters 50 (2009) 2342–2346
2345
Table 2
1
5
Suzuki-Miyaura cross coupling with dtbpx
2
% Pd(OAc) , 2% dtbpx, 2 eq. K PO H O
2
3
4.
2
Ar-X
Ar-Ar'
6
4
Ar'-B(OH)
2
, THF, RT, 48 hr
0
Entry
1
Ar-X
Ar -B(OH)
2
Product 6
Isolated yield of 2 (%)
B(OH)2
B(OH)2
I
O
90
O
I
O
2
3
4
5
6
7
8
9
90
94
90
85
82
88
65
79
93
90
80
75
35
80
O
O
O
B(OH)2
I
O
O N
2
O N
2
B(OH)2
Br
Br
O
B(OH)2
OMe
MeO
O
B(OH)2
Br
Br
O
B(OH)2
OMe
MeO
O
B(OH)2
Br
Br
O
MeO
MeO
MeO
MeO
CF3
B(OH)2
OMe
O
MeO
O
B(OH)2
Br
1
1
1
1
1
1
0
1
2
3
4
5
F3C
F3C
Br
B(OH)2
OMe
CF3
MeO
O
B(OH)2
O
Br
Br
B(OH)2
B(OH)2
B(OH)2
OMe
MeO
MeO
MeO
Cl
OMe
Cl
O
O
OMe
It is not clear whether the active catalytic species in the present
ated. Gibson and co-workers have shown that mono ortho-diph-
enylphosphinotolyl-derived phosphapalladacyclic complexes are
efficient in similar Suzuki cross-couplings with activated aryl bro-
0
system with ligand 1 is a bidentate-Pd complex or a monodentate
Pd(II) species of the type that has been reported,8 nonetheless a
mides. Related species have been generated from both Pd0
8
b
highly active, general and useful Pd-complex of ligand 1 is gener-

2
346
J. McNulty et al. / Tetrahedron Letters 50 (2009) 2342–2346
Klupers, A.; Buchwald, S. L. J. Am. Chem. Soc. 2003, 125, 6653; (n) Aranyos, A.;
2 3
(dba)
)8b through oxidative addition as well as from
sources (Pd
Pd(II) sources (Pd(TFA)
8c
Old, D. W.; Kiyomori, A.; Wolfe, J. P.; Sadighi, J. P.; Buchwald, S. L. J. Am. Chem.
Soc. 1999, 121, 4369; (o) Martin, R.; Buchwald, S. L. Acc. Chem. Res. 2008, 41,
2
). However, in the work of Gibson
8
b
et al., 4-chloroacetophenone did not react with phenylboronic
acid compared with 80% conversion (Table 2, entry 15) with the
present dtbpx system. These workers also showed that the di-
tert-butylphosphinotolyl palladacycle was effective in the coupling
of 4-chlorobenzaldehyde to phenylboronic acid. The available evi-
dence on the presently reported reactivity of Pd-complexes of
dtbpx 1 in the carbonylative and Suzuki-Miyaura cross-coupling
reactions is consistent with the involvement of a doubly ortho-
metalated bimetallic Pd(II) complex of 1 formed in situ from
1461; (p) Fu, G. C. Acc. Chem. Res. 2008, 41, 1555; (q) Billingsley, K.; Buchwald,
S. L. J. Am. Chem. Soc. 2007, 129, 3358.
4.
(a) Portnoy, M.; Milstein, D. Organometallics 1993, 12, 1665; (b) Hills, I.
D.; Netherton, M. R.; Fu, G. C. Angew. Chem., Int. Ed. 2003, 42, 5749; (c)
Galardon, E.; Ramdeehul, S.; Brown, J. M.; Cowley, A.; Hii, K.; Jutand, A.
Angew. Chem., Int. Ed. 2002, 41, 1760; (d) Tschoerner, M.; Pregosin, P. S.;
Albinati, A. Organometallics 1999, 18, 670; Alcazar-Roman, L. M.; Hartwig,
J. F. J. Am. Chem. Soc. 2001, 123, 12905; (e) Clarke, M. L.; Heydt, M.
Organometallics 2005, 24, 6475.
5. (a) Meerwin, R. K.; Schnabel, R. C.; Koola, J. D.; Roddick, D. M. Organometallics
992, 11, 2972; (b) Brown, J. M.; Guiry, P. J. Inorg. Chim. Acta 1994, 220, 249; (c)
Mann, G.; Shelby, Q.; Roy, A. H.; Hartwig, J. F. Organometallics 2003, 22, 2775;
d) Culkin, D. A.; Hartwig, J. F. Organometallics 2004, 23, 3398.
1
8
a
Pd(OAc)
2
.
Nonetheless, Suzuki–Miyaura cross-coupling reactions
(
0
normally proceed via Pd -mediated catalytic cycles raising ques-
6. (a) Eastham, G. R.; Tooze, R. P.; Kilner, M.; Foster, D. F.; Cole-Hamilton, D. J. J.
Chem. Soc., Dalton Trans 2002, 1613; (b) Jimenez-Rodriguez, C.; Foster, D. F.;
Eastham, G. R.; Cole-Hamilton, D. J. Chem. Commun 2004, 1720; (c) Rucklidge,
A. J.; Eastham, G. R.; Cole-Hamilton, D. J. Int. Pat, WO2004050599, 2004; (d)
Rucklidge, A. J.; Morris, G. E.; Slawin, A. M. Z.; Cole-Hamilton, D. J. Helv. Chim.
Acta 2006, 89, 1783; (e) Jimenez-Rodriguez, C.; Eastham, G. R.; Cole-Hamilton,
D. J. Inorg. Chem. Commun. 2005, 8, 878; (f) Ooka, H.; Inoue, T.; Itsuno, S.;
Tanaka, M. Chem. Commun. 2005, 1173.
tions as to the nature of the catalytic cycle. Similar questions were
raised on the Heck reaction using related Pd(II) complexes.8c Work
is currently in progress to identify the formation and involvement
of such a species in the present system.
8
a
In summary, we have demonstrated the efficacy of dtbpx 1 in
palladium-catalysed carbonylative and Suzuki–Miyaura cross-cou-
pling. A range of electron-rich and electron-deficient aryl as well as
vinyl substrates are tolerated in hydroxy-, alkoxy- and aminocarb-
onylation reactions, while aryl chlorides and triflates are more
problematic. The scope of the Suzuki–Miyaura reaction with dtbpx
is shown to be quite broad with, in addition to aryl iodides and bro-
mides, activated aryl chlorides readily entering the catalytic cycle;
and deactivated aryl chlorides to a lesser extent. Further study into
the scope of cross-coupling and the nature of the active catalyst
system in the present case is in progress.
7.
Jimenez-Rodriguez, C.; Pogorzelec, P. J.; Eastham, G. R.; Slawin, A. M. Z.; Cole-
Hamilton, D. J. J. Chem. Soc., Dalton Trans. 2007, 4160.
8.
(a) Clegg, W.; Eastham, G. R.; Elsegood, M. R. J.; Tooze, R. P.; Wang, X. L.;
Whiston, K. W. Chem. Commun. 1999, 1877; (b) Gibson, S.; Foster, D. F.;
Eastham, G. R.; Tooze, R. P.; Cole-Hamilton, D. J. Chem. Commun. 2001, 779; (c)
Ohff, M.; Ohff, A.; van der Boom, M. E.; Milstein, D. J. Am. Chem. Soc. 1997, 119,
1
1687.
(a) Tremblay, J. F. Chemical Engineering News, November 17th, 2008, Vol. 86, p.
(b) New MMA Technology, European Chemical News, October 30th–
November 5th, 2000, p. 20.
9.
8;
1
1
1
1
0. Eastham, G. R.; Heaton, B. T.; Iggo, J. A.; Tooze, R. P.; Whyman, R.; Zacchini, S.
Chem. Commun. 2000, 609.
1. Jimenez-Rodriguez, C.; Eastham, G. R.; Cole-Hamilton, D. J. J. Chem. Soc., Dalton
Trans. 2005, 1826.
2. Morris, D. J.; Docherty, G.; Woodward, G.; Wills, M. Tetrahedron Lett. 2007, 48,
Acknowledgements
949.
3. (a) Beller, M.; Magerlein, W.; Indolese, A. F.; Fischer, C. Synthesis 2001, 1098;
(b) Magerlein, W.; Indolese, A. F.; Beller, M. Angew. Chem., Int. Ed. 2001, 40,
2856; (c) Magerlein, W.; Indolese, A. F.; Beller, M. J. Organomet. Chem. 2002,
We thank NSERC, Cytec Canada Inc. and McMaster University
for financial support of this work.
6
41, 330.
1
4. Sample procedure for carbonylative cross coupling: Synthesis of butyl 4-
methylbenzoate (Table 1, entry 1). 4-Iodotoluene (100.0 mg, 0.459 mmol),
palladium (II) acetate (2.6 mg, 0.0114 mmol) and bis(di-tert-butylphosphino)-
o-xylene (9.0 mg, 0.0229 mmol) were added consecutively to a steel reactor in
a glove box under nitrogen, followed by 1 ml dry DMF (2 ml/mmol), butanol
References and notes
1
.
(a) Adjabeng, G.; Brenstrum, T.; Wilson, J.; Frampton, C. S.; Robertson, A. J.;
Hillhouse, J.; McNulty, J.; Capretta, A. Org. Lett. 2003, 5, 953; (b) Ohnmacht, S.
A.; Brenstrum, T.; Bleicher, K. H.; McNulty, J.; Capretta, A. Tetrahedron Lett.
2 3
(84 ll, 0.917 mmol) and Cs CO (22.4 mg, 0.688 mmol). The reactor was then
2
004, 45, 5661; (c) Adjabeng, G.; Brenstrum, T.; Frampton, C. S.; Robertson, A. J.;
sealed, removed from the glove box and connected via Swage line to a mini
cylinder of CO. After three purges, the reactor was pressurised to 40 psi,
submerged in an oil bath set at 80 °C and stirred via an internal magnet. After
ꢀ8 h, TLC (10% EtOAc/Hex) indicated the reaction to be complete. The mixture
Hillhouse, J.; McNulty, J.; Capretta, A. J. Org. Chem. 2004, 69, 5082; (d)
Brenstrum, T.; Gerritsma, D. A.; Adjabeng, G.; Frampton, C. S.; Robertson, A. J.;
Hillhouse, J.; McNulty, J.; Capretta, A. J. Org. Chem. 2004, 69, 5082; (e)
Brenstrum, T.; Clattenburg, J.; Britten, J.; Zavorines, S.; Dyck, J.; Robertson, A. J.;
McNulty, J.; Capretta, A. Org. Lett. 2006, 8, 103.
was diluted with 2 ml saturated NH
4
Cl, extracted with ethyl acetate (3 ꢁ 5 ml),
the combined organic fractions dried over anhydrous Na
2
4
SO , filtered and
2
.
.
(a) McNulty, J.; Capretta, A.; Wilson, J.; Dyck, J.; Adjabeng, G.; Robertson, A. J.
Chem. Commun. 2002, 1986; (b) Gerritsma, D. A.; Robertson, A. J.; McNulty, J.;
Capretta, A. Tetrahedron Lett. 2004, 45, 7629–7631; (c) McNulty, J.; Cheekoori,
S.; Nair, J. J.; Larichev, V.; Capretta, A.; Robertson, A. J. Tetrahedron Lett. 2005, 46,
concentrated under vacuum into an amorphous residue which was
chromatographed (10% EtOAc/Hex) on silica to give butyl 4-methylbenzoate
in 95% yield. 1H NMR (CDCl
, 200 MHz); d(ppm): 7.93 (2H, d, J = 8.0 Hz), 7.22
(2H, d, J = 8.0 Hz), 4.30 (2H, t, J = 6.0, 6.0 Hz), 2.40 (3H, s), 1.74 (2H, m), 1.47
(2H, m), 0.97 (3H, t, J = 7.3, 7.3 Hz). 13C NMR (CDCl
, 50 MHz); d (ppm): 166.8
3
3
641; (d) McNulty, J.; Nair, J. J.; Cheekoori, S.; Larichev, V.; Capretta, A.;
3
Robertson, A. J. Chem. Eur. J. 2006, 12, 9314; (e) McNulty, J.; Cheekoori, S.;
Bender, T. P.; Coggan, J. A. Eur. J. Org. Chem. 2007, 9, 1423; (f) McNulty, J.; Nair, J.
J.; Robertson, A. J. Org. Lett. 2007, 9, 4575.
(s), 143.4 (s), 129.6 (2 ꢁ d), 129.0 (2 ꢁ d), 127.8 (s), 64.6 (t), 30.8 (t), 21.6 (q),
+
19.3 (t), 13.8 (q). CIMS 70 eV, m/z (rel. int.): 193 [M+1] (20), 136 (46), 119
(100), 91 (30).
3
(a) Wolfe, J. P.; Singer, R. A.; Yang, B. H.; Buchwald, S. L. J. Am. Chem. Soc. 1999,
15. General procedure for Suzuki–Miyaura cross-coupling reaction: The aryl halide
(1 mmol), boronic acid (1.2 mmol), palladium acetate (0.02 mmol), bis(di-tert-
121, 9550; (b) Wolfe, J. P.; Tomori, H.; Sadighi, J. P.; Yin, J. J.; Buchwald, S. L. J.
Org. Chem. 2000, 65, 1158; (c) Streiter, E. R.; Blackmond, D. G.; Buchwald, S. L. J.
Am. Chem. Soc. 2003, 125, 13978; (d) Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem.
Soc. 2000, 122, 4020; (e) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 1998, 37,
3 4
butylphosphino)-o-ylene (0.02 mmol) and K PO -monohydrate (2 mmol) were
weighed into a reaction vial in a glove box under nitrogen. The vial was then
capped, removed from the glove box and flushed with argon (3 cycles). Dry
degassed THF (1.5 ml) was introduced and the mixture stirred under argon at
3
387; (f) Littke, A. F.; Fu, G. C. J. Org. Chem. 1999, 64, 10; (g) Hartwig, J. F.;
Kawatsura, M.; Hauck, S. I.; Shaughnessy, K. H.; Alcazar-Roman, L. M. J. Org.
Chem. 1999, 64, 5575; (h) Nishiyama, M.; Yamamoto, T.; Koie, Y. Tetrahedron.
Lett. 1998, 39, 617; (i) Leadbeater, N. E. Chem. Commun. 2005, 2881; (j) Wolfe, J.
P.; Buchwald, S. L. J. Org. Chem. 1996, 61, 9550; (k) Wolfe, J. P.; Buchwald, S. L. J.
Org. Chem. 2000, 65, 1144; (l) Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am.
Chem. Soc. 1998, 120, 9722; (m) Huang, X.; Anderson, K. W.; Zim, D.; Jiang, L.;
rt for 48 h. After this time, the solution was diluted with 3 ml saturated NH
and extracted with 5 ml ethyl acetate (3 times), the combined organic layers
were dried (Na SO ), filtered and solvent removed under vacuum. The biaryl
products were purified by flash chromatography (10% EtOAc/hexane) on silica
gel.
4
Cl
2
4