Palladium-catalyzed arylation of tert-cyclobutanols with aryl bromide via C-C bond cleavage: New approach for the γ-arylated ketones [5]

Full text of DOI:10.1021/ja993023q

11010
J. Am. Chem. Soc. 1999, 121, 11010-11011
Scheme 1
Palladium-Catalyzed Arylation of tert-Cyclobutanols
with Aryl Bromide via C-C Bond Cleavage: New
Approach for the γ-Arylated Ketones
Takahiro Nishimura and Sakae Uemura*
Department of Energy and Hydrocarbon Chemistry
Graduate School of Engineering, Kyoto UniVersity
Sakyo-ku, Kyoto 606-8501, Japan
ReceiVed August 20, 1999
Table 1. Palladium-Catalyzed Arylation of tert-Cyclobutanolsa
Palladium-catalyzed arylation of a wide variety of compounds
with aryl halide has been developed in recent years as a powerful
method to create an aromatic carbon-carbon bond1 as well as
an aromatic carbon-heteroatom bond.2
Recently, we have reported the palladium(II)-catalyzed oxida-
tive ring cleavage of tert-cyclobutanols using oxygen as a
reoxidant (Scheme 1),3 in which we postulated that the C-C bond
of tert-cyclobutanols was easily cleaved via â-carbon elimination
from a Pd(II) alcoholate formed in situ to give a less hindered
primary alkylpalladium intermediate. In this reaction, we sug-
gested that divalent palladium works as an active species
throughout the reaction using oxygen as a reoxidant. On the other
hand, aryl halide is a well-known reagent for the oxidative reaction
of Pd(0) to Pd(II).1 Thus, our attention turned to the combination
of Pd(0) and aryl halide in the reaction of tert-cyclobutanols,
in which it is expected that arylation via â-carbon elimination
from a Pd(II) alcoholate can proceed. Now we report a novel
palladium-catalyzed arylation of tert-cyclobutanols involving
selective â-carbon elimination from an arylpalladium alcoholate.
Recent advances in palladium-catalyzed arylation of alcohols
with aryl halide for diaryl ether or aryl alkyl ether synthesis have
been reported by Hartwig et al. and Buchwald et al.4 They showed
that a Pd(II) alcoholate is a key intermediate in which reductive
elimination of C-O bond gives a product ether and also that a
bulky or a chelating ligand can accelerate the reductive elimination
step and retard â-hydrogen elimination relative to reductive
elimination.4a,c,5 Thus, our initial attempt to find the efficient
catalyst system was done with 3-tert-butyl-1-phenyl-1-cyclobu-
tanol (1a) as a substrate, using a palladium catalyst and various
kinds of chelating phosphine ligands. The choice of ligands seems
to be a crucial factor because an alkylpalladium intermediate
formed by â-carbon elimination from a Pd(II) alcoholate could
undergo both reductive elimination and â-hydrogen elimina-
entry
ligand
GLC yield (%)
1
2
3
4
5
dppe
dppp
dppb
dppf
63
35
23
59
71
(R)-(+)-BINAP
a Reaction conditions: alcohol (0.20 mmol), Pd2(dba)3‚CHCl3 (0.001
mmol), ligand (0.004 mmol), bromobenzene (0.22 mmol), K2CO3 (0.22
mmol), 1,4-dioxane (1 mL), 100 °C, 12 h, under N2.
tion. Treatment of 1a6 with 1.1 equiv of both bromobenzene and
K2CO3 in the presence of 1 mol % Pd2(dba)3‚CHCl3 and 2 mol
% phosphine ligand in 1,4-dioxane at 100 °C for 12 h under N2
atmosphere afforded 4,4-dimethyl-1-phenyl-3-(phenylmethyl)-1-
pentanone (1b) (Table 1). Among the ligands examined, (R)-
(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP)7 was
revealed to be the most efficient for the arylation of tert-
cyclobutanol 1a (71% GLC yield, entry 5).8 Although a pro-
duced ketone 1b has a chiral carbon center, no asymmetric
induction occurred under these conditions.9 As a solvent for
this reaction, 1,4-dioxane was revealed to be more efficient
than 1,2-dimethoxyethane, N,N-dimethylformamide, and toluene.
Potassium carbonate (K2CO3) was a base of choice, and other
bases, such as Na2CO3, NaOAc, Cs2CO3, and Et3N, were less
effective.
The arylation of siloxycyclopropanes in hexamethylphosphoric
triamide (HMPA) was explored by Nakamura and Kuwajima et
al. in 1988, in which a C-C bond of cyclopropane ring is cleaved
catalytically by an arylpalladium complex to create an aryl
carbon-alkyl carbon bond.10 This reaction is suggested to occur
by direct electrophilic attack of the arylpalladium cationic complex
to an electron-rich â-carbon atom of siloxycyclopropanes to give
an alkylpalladium intermediate, from which reductive elimination
occurs to afford a â-arylated ketone. Their reaction requires a
cationic complex produced from [PdCl(C3H5)]2, triphenylphos-
phine, and aryl triflate, while aryl halide failed to react with
(1) Tsuji, J. In Palladium Reagents and Catalysis; John Wiley: New York,
1995.
(2) For reviews, see: (a) Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.;
Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805. (b) Hartwig, J. F. Angew.
Chem., Int. Ed. 1998, 37, 2046. (c) Hartwig, J. F. Synlett 1997, 329. (d)
Hartwig, J. F. Acc. Chem. Res. 1998, 31, 852. (e) Yang, B. H.; Buchwald, S.
L. J. Organomet. Chem. 1999, 576, 125.
(3) Nishimura, T.; Ohe, K.; Uemura, S. J. Am. Chem. Soc. 1999, 121, 2645.
(4) For recent advances in palladium-catalyzed arylation of alcohols with
aryl halide to produce aryl ethers, see: (a) Palucki, M.; Wolfe, J. P.; Buchwald,
S. L. J. Am. Chem. Soc. 1996, 118, 10333. (b) Mann, G.; Hartwig, J. F. J.
Am. Chem. Soc. 1996, 118, 13109. (c) Palucki, M.; Wolfe, J. P.; Buchwald,
S. L. J. Am. Chem. Soc. 1997, 119, 3395. (d) Widenhoefer R. A.; Zhong, H.
A.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 6787. (e) Mann, G.; Hartwig,
J. F. J. Org. Chem. 1997, 62, 5413. (f) Mann, G.; Hartwig, J. F. Tetrahedron
Lett. 1997, 38, 8005. (g) Widenhoefer R. A.; Buchwald, S. L. J. Am. Chem.
Soc. 1998, 120, 6504. (h) Mann, G.; Incarvito, C.; Rheingold, A. L.; Hartwig,
J. F. J. Am. Chem. Soc. 1999, 121, 3224. (i) Aranyos, A.; Old, D. W.;
Kiyomori, A.; Wolfe, J. P.; Sadighi, J. P.; Buchwald, S. L. J. Am. Chem. Soc.
1999, 121, 4369.
(5) For examples of C-C reductive elimination, which is much faster than
â-hydrogen elimination in palladium-catalyzed arylation of ketones, see: (a)
Palucki, M.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 11108. (b)
Hammann, B. C.; Hartwig J. F. J. Am. Chem. Soc. 1997, 119, 12382. (c)
Åhman, J.; Wolfe, J. P.; Troutman, M. V.; Palucki, M.; Buchwald, S. L. J.
Am. Chem. Soc. 1998, 120, 1918. (d) Kawatsura, M.; Hartwig, J. F. J. Am.
Chem. Soc. 1999, 121, 1473.
(6) Cyclobutanols are readily accessible from the corresponding cyclobu-
tanones and Grignard reagent. For typical methods for preparing cyclobu-
tanones, see: (a) Krepski, L. R.; Hassner, A. J. Org. Chem. 1978, 43, 2879.
(b) Greene, A. E.; Luche, M.-J.; Serra, A. A. J. Org. Chem. 1985, 50, 3957.
(7) Racemic BINAP can also be used as a ligand. For the other ligands,
dppe, dppp, dppb, and dppf stand for 1,2-bis(diphenylphosphino)ethane, 1,3-
bis(diphenylphosphino)propane, 1,4-bis(diphenylphosphino)butane, and 1,1′-
bis(diphenylphosphino)ferrocene, respectively.
(8) Although Pd(OAc)2 can also be used for the arylation of 1a, the yield
of 1b decreased (58% GLC yield). The reaction can also proceed with Pd-
(PPh3)4 (65% GLC yield of 1b).
(9) The enantiomeric excess was measured by HPLC.
(10) Aoki, S.; Fujimura, T.; Nakamura, E.; Kuwajima, I. J. Am. Chem.
Soc. 1988, 110, 3296.
10.1021/ja993023q CCC: $18.00 © 1999 American Chemical Society
Published on Web 11/12/1999

Communications to the Editor
J. Am. Chem. Soc., Vol. 121, No. 47, 1999 11011
Table 2. Palladium-Catalyzed Arylation of tert-Cyclobutanolsa
Scheme 2. Plausible Reaction Pathway
siloxycyclopropanes. In contrast, in our reaction, the arylation of
tert-cyclobutanols proceeds with aryl bromide, because the
formation of a Pd(II) alcoholate between a neutral palladium
species and an alcohol is a crucial step which is followed by
â-carbon elimination (vide infra).
The results of arylation of several monocyclic tert-cyclobu-
tanols leading to γ-arylated ketone under the optimized conditions
described above are listed in Table 2. Using bromobenzene as
an arylating reagent, 3-substituted cyclobutanols 1a and 2a gave
the corresponding γ-arylated ketones 1b and 2b in good yields
(entries 1 and 3).11 3,3-Disubstituted cyclobutanols 3a-5a also
afforded the corresponding ketones 3b, 4b, and 5b in high yields.
The arylation of 1a and 4a with 2-bromonaphthalene could also
proceed to afford ketones 1c and 4c in good yields (entries 2 and
6). Similarly, the reaction of 4a with p-bromotoluene smoothly
occurred to give 4d in high yield (entry 7). p-Bromochlorobenzene
afforded 4e selectively without affecting the chloro substituent
(entry 8). The reaction could also be applied to bicyclic cyclobu-
tanols 6a-8a (eqs 1 and 2). In contrast to monocyclic cyclobu-
a Reaction conditions: alcohol (0.4 mmol), Pd2(dba)3‚CHCl3 (0.002
mmol), (R)-(+)-BINAP (0.008 mmol), aryl bromide (0.44 mmol),
K2CO3 (0.44 mmol), 1,4-dioxane (2 mL), 100 °C, 12 h, under N2. b 1.2
equiv of both aryl bromide and K2CO3 to alcohol were used. c GLC
yield.
complex, occurred to give arylated ketones 6b-8b in high yields,
in which an initial configuration (cis-configuration at bridgehead
carbons in a substrate) was kept during the reaction.12
The formation of a ring-opening arylated ketone can be
explained by assuming the reaction sequence shown in Scheme
2. An arylpalladium intermediate, formed by oxidative addition
of aryl bromide to a palladium(0) phosphine complex, undergoes
a ligand exchange with tert-cyclobutanol to afford a palladium
alcoholate 9, which gives an alkylpalladium intermediate 10 by
â-carbon elimination. The species 10 is prone to eliminate a
palladium(0) phosphine complex reductively to give γ-arylated
ketones. The fact that no aryl ether formation was observed
suggests that â-carbon elimination is much faster than reductive
elimination of an aryl C-O bond. Furthermore, the results of the
reactions of 1a, 2a, 6a, and 8a clearly show that reductive
elimination from 10 is much faster than â-hydrogen elimination
to give an alkene.
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tanols, bicyclic ones have two C-C bonds in the ring that may
be cleaved. In these cases, a selective C-C bond cleavage of
cyclobutanol, giving a less hindered primary alkylpalladium
(11) In the case of 1a, the formation of a small amount of 3,4,4-trimethyl-
1-phenyl-2-penten-1-one (<3%) was detected by 1H NMR analysis of the
crude reaction mixture. It may be formed by isomerization from an initially
formed â,γ-unsaturated ketone via â-hydrogen elimination from an alkylpal-
ladium intermediate. Similarly, from the reaction of 2a, 3-methyl-1,3-diphenyl-
2-buten-1-one was isolated in 6% yield.
JA993023Q
(12) The stereochemistry of 6b, 7b, and 8b was confirmed by the
observation of the different NOE spectra (methine protons for 6b and 8b,
methyl and methine protons for 7b, respectively, in these NMR spectra).