528
Chemistry Letters Vol.36, No.4 (2007)
Palladium-catalyzed Nucleophilic Substitution of Diarylmethyl Carbonates
with Malonate Carbanions
Ryoichi Kuwanoà and Hiroki Kusano
Department of Chemistry, Graduate School of Sciences, Kyushu University,
6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581
(Received January 22, 2007; CL-070072; E-mail: rkuwascc@mbox.nc.kyushu-u.ac.jp)
The nucleophilic substitution of diarylmethyl carbonates
Table 1. Effect of phosphine ligand on the reaction of 1a
with 2aa
with malonate carbanions proceeded in the presence of [Pd(ꢀ-
C3H5)(cod)]BF4–Cy-Xantphos, giving the desired (diaryl-
methyl)malonates in up to 90% yield. The yield was extremely
affected by choice of the phosphine ligand.
5% cat.
Ph
CO2Me
Ph
Ph
CO2Me
CO2Me
Ph
Ph
[Pd] – ligand
OCOMe +
+
O
Na2CO3
DMF
Ph
CO2Me
O
2
1a
Ph2P
2a
3a
4
120 °C, 3 h
Nucleophilic substitution is a fundamental reaction in or-
ganic synthesis.1 Alkyl halides or sulfonates have been chosen
for an electrophilic substrate commonly. Carboxylate function-
ality has seldom been utilized as a leaving group on the electro-
philic substrate because of its low reactivity. Anomalistically,
substitution of allylic carboxylates has often been utilized in or-
ganic synthesis by means of homogeneous palladium catalysis.2
Palladium(0) cleaves the allylic C–O bond to form (ꢀ-allyl)-
palladium intermediate, which readily reacts with various
nucleophiles. Meanwhile, we reported recently that a palladi-
um-catalyzed nucleophilic substitution of benzylic carbon-
ates.3–5 As with the catalytic allylic substitution, the benzylic
C–O bond was activated by palladium(0) to provide (ꢀ-benzyl)-
palladium intermediate. However, the substrates for the catalytic
benzylic substitution have been limited to benzylic esters having
no ꢁ-substituent, with the exception of 1-(naphthyl)ethyl ace-
tates.4,6 This paper describes a palladium-catalyzed nucleophilic
substitution of benzylic carbonates possessing an aryl substituent
at the ꢁ-position, i.e. diarylmethyl esters.
Reaction of diphenylmethyl carbonate 1a with malonate 2a
was attempted under various reaction conditions. The desired
(diphenylmethyl)malonate 3a was obtained in 80% yield when
the reaction was conducted in DMF at 120 ꢀC in the presence
of sodium carbonate and 5 mol % of the palladium complex
generated from [Pd(ꢀ-C3H5)(cod)]BF4 and a bidentate ligand
Cy-Xantphos (Table 1, Entry 8). The choice of ligand on palla-
dium is crucial for the benzylic substitution of 1a. Triphenyl-
phosphine–palladium catalyst produced no 3a and a small
amount of bis(diphenylmethyl) ether (4) (Entry 1). The produc-
tion of 3a was not achieved by using chelate ligands bearing two
diphenylphosphino groups (Entries 2–5). Only Xantphos7 gave
3a in recognizable yield (10%), but 4 was obtained preferentially
(Entry 6). The undesirable formation of 4 was successfully evad-
ed with cyclohexyl-substituted bisphosphine ligands (Entries 7
and 8). Cy-Xantphos afforded 3a in 80% yield at 24 h. However,
the benzylic substitution of 1a was remarkably hindered by
bulky tert-butyl groups of t-Bu-Xantphos (Entry 9). The palladi-
um catalysis was strongly affected by base and solvent. Sodium
carbonate is the base of choice. Potassium carbonate could give
3a but seemed to cause decomposition of the palladium catalyst
(Entry 10). Use of nitrogen compounds as a base obstructed
consumption of 1a (Entry 11). Methoxide librated from 1a might
be possible to serve as a base for generating malonate carbanion,
PPh2
n
O
DPPB (n = 4)
DPEphos (R = Ph)
DPPPent (n = 5)
Cy-DPEphos (R = c-Hex)
R2P
PR2
Me Me
PPh2
Fe
Xantphos (R = Ph)
PPh2
O
Cy-Xantphos (R = c-Hex)
t-Bu-Xantphos (R = t-Bu)
R2P
PR2
DPPF
Entry
Ligand
c
Yield (3a)/%b
Yield (4)/%b
1
2
3
4
5
6
7
8
9
PPh3
DPPB
DPPPent
0
1
2
2
2
6
12
13
23
9
26
7
3 (8)
0
DPPF
DPEphos
Xantphos
Cy-DPEphos
Cy-Xantphos
t-Bu-Xantphos
Cy-Xantphos
Cy-Xantphos
10
10
31 (80)
2
38 (44)
9
10d
11e
3 (8)
6
aReactions were conducted in DMF (1.0 mL). [Pd(ꢀ-C3H5)(cod)]-
BF4 was used as a palladium catalyst precursor. The ratio of 1a
(0.20 mmol):2a:Na2CO3:[Pd]:ligand was 20:30:30:1:1.1. bGC
yield at 3 h (average of two runs). GC yields at 24 h were given
c
in parentheses. The ratio of [Pd]:PPh3 was 1:2.2. dK2CO3 was
e
used in place of Na2CO3. DBU was used in place of Na2CO3.
but 3a was obtained in 3% yield with no base.8 The reaction of
1a with 2a barely proceeded in solvents other than DMF. Base
and solvent did not affect the production of the side product
4 much. The catalytic alkylation of 2a with 1a proceeded
with 1% catalyst loading, affording 3a in 90% isolated yield
(Table 2, Entry 1).
As shown in Table 2, the benzylic substitutions of other
diarylmethyl carbonates with malonates were attempted under
the reaction conditions optimized above. Electron-rich substrate
1b, which have a methoxy group, was converted into 3b in 55%
yield (Entry 2). Further introduction of a methoxy group on
another benzene ring of 1 resulted in remarkable decrease in
the yield of 3 (Entry 3). The electron-donating group caused
the formation of diarylmethyl methyl ether, which was generated
through thermal decarboxylation. In contrast, no reactions were
Copyright Ó 2007 The Chemical Society of Japan