Scheme 1
.
Possible Pathway of the Palladium-Catalyzed
Table 1. Effect of Catalyst on the Reaction of 2aa
Nucleophilic Substitution of Benzyl Methyl Carbonates 1
entry
[Pd]
ligand
yield (3a), %b
1
2
3
4
5
6
7
8e
9
Pd(η3-C3H5)Cp
Pd(η3-C3H5)Cp
Pd(η3-C3H5)Cp
Pd(η3-C3H5)Cp
Pd(η3-C3H5)Cp
Pd(η3-C3H5)Cp
Pd(η3-C3H5)Cp
Pd(OAc)2
DPEphos
Xantphos
DPPF
DPPPent
DPPB
99 (99)c
nucleophilic species. We envisioned that in the absence of
pronucleophile, the catalytic reaction would provide benzyl
methyl ether via alkoxide attack to the η3-benzyl ligand. Such
a decarboxylative etherification would be useful for the
benzyl protection of alcohols if the reaction would occur in
various alkyl and/or aryl benzyl carbonates. Here, we report
a decarboxylative etherification of aryl benzyl carbonates by
means of the palladium catalysis, which afforded a broad
range of benzyl-protected phenols in high yield. Additionally,
the palladium catalyst is effective for the direct benzyl
protection of phenols with benzyl methyl carbonate. Both
etherifications do not require any additives other than the
palladium catalyst.10
95 (38)c
97 (4)c
11
66
6
0
0
DPPP
d
PPh3
DPEphos
DPEphos
Pd(dba)2
0
a Reactions were conducted on a 0.2 mmol scale in toluene (1.0 mL) at
80 °C for 3 h. The ratio of 2a/[Pd]/ligand was 20:1.0:1.1. b GC yield (average
of two runs). c Yields in parentheses are GC yields of the reactions at 60
°C. d Ratio of [Pd]/PPh3 was 1.0:2.2. e Et3N (20 µmol) was added to the
reaction mixture to reduce Pd(OAc)2 to Pd(0).
phine ligands (entry 7). Choice of palladium precursor was
crucial for the catalytic reaction. The substrate 2a was
scarcely consumed when it was treated with the palladium
catalyst prepared from Pd(OAc)2 or Pd(dba)2. The hemilabile
ligands constituting these catalyst precursors might obstruct
the interaction between palladium(0) and the benzyl carbon-
ate. The catalyst loading was successfully reduced to 1.0%
without significant loss of the yield of 3a (Table 2, entry 1).
As shown in Table 2, a wide range of aryl benzyl
carbonates 2 were transformed into the benzyl ethers in high
yield by Pd(η3-C3H5)Cp–DPEphos catalyst. Electron-donat-
ing or electron-withdrawing property of the p-substituent of
2c-e hardly caused significant decrease in the yield of 3
(entries 3-5). The decarboxylative etherification of 4-methyl-
or 4-nitrophenyl carbonate failed to give 3b or 3f in
acceptable yield when the reactions were conducted in the
presence of 1.0% palladium. However, higher yield of the
benzyl ethers was obtained with 5% catalyst loading (entry
2 and 6). Two ortho-methyl groups of 2h did not hinder the
catalytic production of 3h (entry 8). Double etherification
of 2k proceeded well, affording benzyl-protected biphenol
3k (eq 1). Benzyl 2-naphthyl carbonate was converted into
the desired ether in only 46% yield. The low yield was caused
by undesirable benzylation at the 1-position on the naph-
thalene ring.13a Alkyl benzyl carbonates did not work as
substrates for the catalytic reaction. Treatment of benzyl
cyclohexyl carbonate with the palladium catalyst yielded no
benzyl cyclohexyl ether. Hardness of the alkoxides might
reduce their nucleophilicity for the (η3-benzyl)palladium
intermediate. The present decarboxylative formation of
benzyl ethers is applicable to protection of phenols with
In a series of our studies on the palladium-catalyzed
transformations of 1,8 we have never observed the formation
of benzyl methyl ether.11 Consequently, we evaluated various
palladium complexes for the reaction of benzyl phenyl
carbonate (2a), because softer phenoxide would be more
reactive to the η3-benzyl ligand on palladium than harder
methoxide (Table 1).12,13 The quantitative formation of
benzyl phenyl ether (3a) was observed at 80 °C in the
reaction using the palladium catalyst, which was generated
in situ from Pd(η3-C3H5)Cp14 and a bisphosphine ligand,
DPPF,15 DPEphos,16 or Xantphos16 (entries 1-3). In par-
ticular, the DPEphos–palladium catalyst produced the desired
ether in high yield even at 60 °C. Use of other bisphosphine
ligands resulted in lower yields (entries 4-6). No benzyl
ether 3a was produced in the reaction employing monophos-
(10) Asao et al. reported a gold-catalyzed etherification using o-
alkynylbenzoates as alkylating agents: Asao, N.; Aikawa, H.; Tago, S.;
Umetsu, K. Org. Lett. 2007, 9, 4299–4302.
(11) Anomalously, formation of a benzylic ether was observed in the
palladium-catalyzed substitution of diarylmethyl carbonates: Kuwano, R.;
Kusano, H. Chem. Lett. 2007, 36, 528–529.
(12) (a) Tsuji, J. In Palladium Reagents and Catalysts; John Wiley &
Sons, Inc.: West Sussex, 2004; Chapter 4, pp 431-517. (b) Trost, B. M.;
Van Vranken, D. L. Chem. ReV. 1996, 96, 395–422
.
(13) (a) Goux, C.; Massacret, M.; Lhoste, P.; Sinou, D. Organometallics
1995, 14, 4585–4593. (b) Trost, B. M.; Tsui, H.-C.; Toste, F. D. J. Am.
Chem. Soc. 2000, 122, 3534–3535
.
(14) Tatsuno, Y.; Yoshida, T.; Otsuka, S. Inorg. Synth. 1979, 19, 220–
223.
(15) DPPF ) 1,1′-bis(diphenylphosphino)ferrocene: Bishop, J. J.; Davi-
son, A.; Katcher, M. L.; Lichtenberg, D. W.; Merrill, R. E.; Smart, J. C. J.
Organomet. Chem. 1971, 27, 241–249.
(16) DPEphos ) bis[2-(diphenylphosphino)phenyl]ether, Xantphos )
9,9-dimethyl-4,6-bis(diphenylphosphino)xanthene: Kranenburg, M.; van der
Burgt, Y. E. M.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Goubitz, K.;
Fraanje, J. Organometallics 1995, 14, 3081–3089.
1980
Org. Lett., Vol. 10, No. 10, 2008