Palladium-catalyzed C-O coupling involving unactivated aryl halides. Sterically induced reductive elimination to form the C-O bond in diaryl ethers [4]

Full text of DOI:10.1021/ja984321a

3
224
J. Am. Chem. Soc. 1999, 121, 3224-3225
Table 1. Palladium-Catalyzed Conversion of Aryl Halides to Aryl
Palladium-Catalyzed C-O Coupling Involving
Unactivated Aryl Halides. Sterically Induced
Reductive Elimination To Form the C-O Bond in
Diaryl Ethers
2 3
Ethers with FcP(t-Bu) or P(t-Bu) As Ligand
‡
†
Grace Mann, Christopher Incarvito,
†
,‡
Arnold L. Rheingold, and John F. Hartwig*
Department of Chemistry, Yale UniVersity
P.O. Box 208107, New HaVen, Connecticut 06520-8107
Department of Chemistry, UniVersity of Delaware
Newark, Delaware 19716
ReceiVed December 17, 1998
The reductive elimination of ethers from transition metal
complexes is a rare elementary reaction that is limited to special
cases.1 The importance of aryl ether substructures has created
a synthetic challenge to prepare the aryl-oxygen linkage in a
-6
7
-11
general fashion under mild conditions.
Pd-catalyzed C-O
coupling4
,12-15
could be a solution to this synthetic problem, but
the reductive elimination of acyclic ethers
4
-6
that is the crucial
step for this catalytic process has been limited to palladium
complexes with aromatic systems that are highly activated and
undergo direct, uncatalyzed nucleophilic aromatic substitution
chemistry. Thus, it is unactivated aryl halides that are crucial
substrates to include in transition metal-catalyzed C-O coupling
chemistry,4
-6,13
and we report that Pd complexes with sterically
hindered alkylphosphines (1) undergo thermal reductive elimina-
tion to form the C-O bond in diaryl ethers from complexes with
unactivated metal-bound aryl groups and (2) catalyze the forma-
tion of diaryl ethers and protected phenols from unactivated aryl
halides. These findings demonstrate the concept that sterically
hindered alkylphosphines accelerate reductive elimination.
a
All the reactions were performed in toluene solvent with a 0.2-
, 2-5 mol %
, and 1.2 equiv of NaOR unless otherwise stated. Ligand 4 is oxygen
0
4
.3 M concentration of aryl halide, 2-5 mol % Pd(dba)
2
sensitive in solution. All reagents were weighed in a glovebox. Isolated
yields were from an average of two runs. b 5 mol % Pd(dba)
2
and 5
3
were used as catalyst. The product was isolated in
mol % P(t-Bu)c
t
Our recent success with D BPF (1,1′-bis(di-tert-butylphos-
>96% purity. After heating, the reaction mixture was treated with
phinoferrocene)) (1) in amination of aryl halides16 led us to seek
CF
3
CO
H and CF
H. d Yield was determined by GC analysis with
2
3
SO
3
improvements in aryl halide etherification using this ligand. The
an internal standard.
reaction in eq 1 containing catalytic amounts of Pd(OAc)
2
and
D BPF gave diaryl ether in 45% yield. The same reaction with
BINAP, DPPF, or P(o-tolyl) as ligand gave no ether. The origin
t
t
catalytic cycle or a D BPF-ligated palladium complex is not the
product-forming intermediate.
3
Careful analysis of all reaction products by GC/MS showed
of this reactivity difference was complex and led to the discovery
of a new ferrocenyl monophosphine.
t
the latter to be true: D BPF cleaved into the two monophosphines,
phenyldi-tert-butylphosphine (3)17 and ferrocenyldi-tert-butylphos-
phine (4). These ligands were prepared, each in one step, and
t
The presumed arylpalladium phenoxide intermediate (D BPF)-
Pd(C
6
H
5
)(O-p-C
6 4
H OMe) (2) was isolated after reaction of
t
used in combination with Pd(OAc)
in eq 1. Reactions catalyzed by 3 and Pd(OAc)
2
as catalyst for the reaction
gave less than
(D BPF)Pd(Ph)(Br) with sodium aryloxide in THF. Surprisingly,
2
thermolysis of 2 at 110 °C in the presence or absence of sodium
aryloxide and added ligand as trap for Pd(0) produced no diaryl
ether. Either reductive elimination does not occur during the
‡
Yale University.
†
University of Delaware.
(
1) Matsunaga, P. T.; Mavropoulos, J. C.; Hillhouse, G. L. Polyhedron
1
995, 14, 175.
2) Koo, K.; Hillhouse, G. L.; Rheingold, A. L. Organometallics 1995,
4, 456.
(
2
5% diaryl ether, but reactions catalyzed by 4 and Pd(OAc) gave
1
(
(
(
3) Han, R.; Hillhouse, G. L. J. Am. Chem. Soc. 1997, 119, 8135.
83% yield of diaryl ether by GC analysis. Thus, palladium
complexes of ligand 4 produce the true catalyst, and this catalyst
is superior to any previous transition metal system for the
formation of diaryl ethers from unactivated aryl halides.
A survey of the catalytic formation of diaryl ethers with ligand
4) Mann, G.; Hartwig, J. J. Am. Chem. Soc. 1996, 118, 13109.
5) Widenhoefer, R. A.; Zhong, H. A.; Buchwald, S. L. J. Am. Chem. Soc.
1
997, 119, 6787.
(6) Widenhoefer, R. A.; Buchwald, S. L. J. Am. Chem. Soc. 1998, 120,
6
504.
(
7) Evans, D. A.; Katz, J. L.; West, T. R. Tetrahedron Lett. 1998, 39, 2937.
8) Marcoux, J. F.; Doye, S.; Buchwald, S. L. J. Am. Chem. Soc. 1997,
4
is provided in Table 1. Reactions were faster when using Pd-
(
1
19, 10539.
(dba) as the palladium source. Aryl bromides or chlorides with
2
(
(
(
(
(
(
9) Bigot, A.; Zhu, J. Tetrahedron Lett. 1998, 39, 551.
electron-withdrawing acyl or electron-donating alkyl groups
reacted to form diaryl ethers in good yields. Aryl iodides gave
low conversions. Aryl halides with ortho substituents reacted faster
10) Pearson, A. J.; Bignan, G. Tetrahedron Lett. 1996, 37, 735.
11) Boger, D. L.; Yohannes, D. J. Org. Chem. 1991, 56, 1763.
12) Mann, G.; Hartwig, J. F. J. Org. Chem. 1997, 62, 5413.
13) Mann, G.; Hartwig, J. F. Tetrahedron Lett. 1997, 38, 8005.
14) Palucki, M.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1996,
(
80 °C) than unhindered aryl halides (110 °C). Similar yields of
diaryl ether were obtained from hindered aryl halides when Pd-
(dba) and ligand 4 or P(t-Bu) were used as catalyst (4 ) 85%,
1
1
18, 10333.
15) Palucki, M.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1997,
19, 3395.
16) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998, 120, 7369.
(
2
3
(
(17) Mann, B. E.; Shaw, B. L.; Slade, R. M. J. Chem. Soc. A 1971, 2976.
1
0.1021/ja984321a CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/17/1999

Communications to the Editor
J. Am. Chem. Soc., Vol. 121, No. 13, 1999 3225
Scheme 1
in 95% yield (eq 2). This observation constitutes the first reductive
elimination of diaryl ether and a rare reductive elimination of
ether with an unactivated aryl group.20 Surprisingly, thermolysis
of 7a without added P(t-Bu) gave diaryl ether in only 25% yield
3
in the presence or absence of sodium aryl oxide, aryl bromide,
or ligand 4 (eq 2). Similarly, 7a generated in situ by addition of
sodium aryl oxide to 6 gave aryl ether in 22% yield. Finally,
reaction of p-tolyl complex 7b in the presence of 10 equiv of
P(t-Bu)
presumably induces elimination of diaryl ether in the presence
of added P(t-Bu) , consistent with lower reaction rates and lower
yields with decreasing quantities of added P(t-Bu) . The instability
of P(t-Bu) -ligated aryl halide complexes prevented direct syn-
thesis of P(t-Bu) -ligated aryl oxide complexes.
The contrast between the modest yield of ether from the
stoichiometric reductive eliminations without added P(t-Bu) and
3
gave diaryl ether in 25% yield. Ligand exchange
3
3
3
3
3
the excellent yields of catalytic reactions with only 4 as ligand
indicates that dimeric 6 and 7 are not the precise intermediates
on the catalytic cycle. Indeed, the proposed catalytic cycle in
Scheme 1 involves monomeric versions of the isolated arylpal-
ladium complexes.21 Monomeric complexes are almost certainly
the intermediate because (1) reductive eliminations are more
common from a single metal center, (2) lower yields and/or slower
rates for the reductive elimination of sulfides and amines from
P(t-Bu) ) 83%), but unhindered aryl halides gave higher yields
3
of diaryl ether when using ligand 4 (4 ) 74%, P(t-Bu) ) 27%).
3
Electron-rich sodium aryl oxides, sodium phenoxide, and a sodium
aryl oxide bearing an ortho methoxy substituent all gave diaryl
ether product in good yields.18
dimeric vs monomeric Pd(II) thiolate and amido complexes have
Aryl halides were also converted to tert-butyl aryl ethers, which
serve as precursors to aryl alcohols, using NaO-t-Bu as reagent
been observed previously,2
2,23
(3) higher yields of the catalytic
chemistry were observed at lower concentrations (82% at 0.2 M
and a catalyst bearing ligand 4 or P(t-Bu)
from ligand 4 and Pd(dba) catalyzed the formation of aryl ether
at a faster rate than that formed from P(t-Bu)
3
. The complex formed
3
1
aryl halide vs 23% at 1 M aryl halide), and (4) P NMR
spectrometry showed that monomeric Pd(0) 5 was the resting
state, creating low concentrations of arylpalladium intermediates
and favoring reactions from monomeric species in solution.
The catalytic and stoichiometric results presented here contrast
the more common C-C bond formation between aryl halides and
2
3
. This type of C-O
bond formation occurred for electron-rich aryl bromides, iodides,
and chlorides, and occurred cleanly to produce O heterocycles.14
In general, a catalyst loading of 2-5% was sufficient for
formation of both diaryl and tert-butyl aryl ethers. Lower catalyst
loads led to longer reaction times. A 1:1 or even a 1:0.5 ratio of
Pd to ligand was sufficient. Entry 9 shows that yields are higher,
temperatures are lower, and times are shorter than previous
2
4-26
phenoxides with use of more conventional arylphosphines.
The difference in products as a function of steric effects shows
that changes in ligand size can dramatically change the chemose-
lectivity of coupling with phenols. Apparently, coordination of
reactions conducted with BINAP15 or DPPF.
13
27,28
ligand 4 or P(t-Bu)
3
to arylpalladium phenoxides makes
With the correct ligand for diaryl ether formation, we prepared
potential reaction intermediates. Palladium(0) complex {Pd-
reductive elimination of ethers much faster than it is from
complexes containing more conventional arylphosphine ligands.
[
(P(Fc)(t-Bu)
reaction of ligand 4 with (η -allyl)(η -cyclopentadienyl)Pd at room
temperature or with Pd[(P(o-tolyl) at 65 °C for 1 h. An X-ray
diffraction study showed a perfectly linear geometry for 5
2 2
)] } (5) was isolated in analytically pure form by
3
5
Acknowledgment. This work was supported by the NIH (R-29-GM
55382) and the DOE.
3
]
2
Scheme 1).19 Dimeric palladium-bromide complex {[Pd(P(Fc)-
t-Bu)
Supporting Information Available: Experimental procedures, spec-
troscopic data, and analytical data for 2 and 4-7; X-ray diffraction data
for 5 and 7b and literature references to previously reported products
(
(
2
)(o-MeC
6
H
4
)(µ-Br)]
2
} (6) was prepared by phosphine
)Pd(Ar)(µ-Br)] . Aryl oxide
](Ar)(µ-O-p-C OMe)} (Ar )
6 4
H , 7b) were synthesized by addition
exchange between 4 and [(P(o-tolyl)
complexes {Pd[P(Fc)(t-Bu)
o-MeC , 7a; Ar ) p-MeC
3
2
(PDF). This material is available free of charge via the Internet at
2
6
H
4
2
http://pubs.acs.org.
H
6 4
JA984321A
of sodium aryl oxide to 6, formed in situ by the phosphine
exchange in THF solvent. The X-ray structure (Scheme 1) of 7b
shows square-planar Pd centers with a sum of the four angles at
the metal equal to 361.7° and a dimeric core with a puckered
(20) Meyer, U.; Werner, H. Chem. Ber. 1990, 123, 697.
(21) Another possibility for forming the true intermediate is an exchange
of phosphorus substituents by P-C cleavage processes to create small
quantities of P(t-Bu) that are bound to the actual catalyst. However, higher
yields and faster rates for the reactions of unhindered substrates with ligand
instead of P(t-Bu) rule out this possibility.
22) Louie, J.; Hartwig, J. F. J. Am. Chem. Soc. 1995, 117, 11598.
(23) Driver, M. S.; Hartwig, J. F. J. Am. Chem. Soc. 1997, 119, 8232.
24) Hennings, D. D.; Iwasa, S.; Rawal, V. H. J. Org. Chem. 1997, 62, 2.
3
19
geometry containing a Pd-O-Pd-O torsion angle of 33.2 °.
Thermolysis of isolated palladium aryl oxide 7a at 70 °C for
0 min in the presence of 20 equiv of P(t-Bu) gave diaryl ether
4
3
(
3
3
(
(
18) Only a trace of the more common product from C-C bond formation
was present in the isolated material.
19) Crystallographic characterization. For (5): monoclinic, C2/c, yellow
blade, a ) 22.4159(2) Å, b ) 10.1684(2) Å, c ) 15.8735(2) Å, â ) 106.9971-
(25) Satoh, T.; Kawamura, Y.; Miura, M.; Nomura, M. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 1740.
(
(26) Satoh, T.; Inoh, J.; Kawamura, Y.; Kawamura, Y.; Miura, M.; Nomura,
M. Bull. Chem. Soc. Jpn. 1998, 71, 2239.
3
(
2)°, V ) 3460.05(6) Å , Z ) 4, R(F) ) 3.36%, GOF ) 1.169. For (7b):
(27) Nishiyama, M.; Yamamoto, T.; Koie, Y. Tetrahedron Lett. 1998, 39,
monoclinic, C2/c, orange irregular block, a ) 20.070(1) Å, b ) 27.723(2) Å,
c ) 14.542(1) Å, â ) 128.047(3)°, V ) 6372.1(7) Å , Z ) 8, R(F) ) 0.056,
617.
3
(28) Yamamoto, T.; Nishiyama, M.; Koie, Y. Tetrahedron Lett. 1998, 39,
GOF ) 1.83.
2367.