ACS Catalysis
as the catalyst precursor (Table 1,
Page 2 of 4
produced with Pd(OAc)
2
formed into methyl hydrogen carbonate and acting as the
activator of amines and then facile the oxidation step.
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entry 4). The reaction efficiency decreased when DPPP,
DPPPe or Xantphos was applied instead of DPPB (Table 1,
entries 5-7). To our surprise, no reaction occurred when using
THF or 1,4-dioxane as reaction solvent (Table 1, entry 8). This
phenomenon implies that DMC might have other role besides
solvent. Carbon monoxide pressure or reaction temperature
variations could not further improve the reaction outcomes
(
Table 1, entry 9). With lower amount of MeOH, yield of the
desired ester slightly decreased (Table 1, entry 10).
At this stage, the optimum reaction conditions were estab-
lished. However, the simple and sustainable conditions for
such challenge benzyl amine activation motivated us to per-
form further control studies to get some understandings of the
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Scheme 2. Proposed reaction mechanism.
reaction pathway (Scheme 1). We suspect that the NH
2
group
of benzyl amine could be methylated by methanol or DMC in
7
,8
In order to proven the synthetic potential of this methodolo-
gy, the testing of different benzyl amines were carried out
under our standard condition as well (Table 2). Primary benzyl
amines can be all effectively transformed in general (Table 2,
entries 1-10). Substrates with substituent at ortho position or
the presence of palladium catalyst. Then the in situ produced
N-methyl or N,N-dimethyl product can be carbonylated to give
the obtained ester. However, N-methyl benzyl amine or/and
N,N-dimethyl benzyl amine could not be detected in the ab-
sence of CO or CO and MeOH (Scheme 1, eq 1 and 2). A
control reaction without MeOH addition has been carried out
as well (Scheme 1, eq 3). Under CO pressure, no methyl 2-
phenylacetate can be detected, but 21% of methyl benzylcar-
bamate was formed which comes from the reaction between
benzyl amine and DMC. The possibility that methyl benzyl-
carbamate acting as the reaction intermediate can be excluded
by the control experiments shown in Scheme 1, eq 4 and 5. No
methyl 2-phenylacetate can be detected under our standard
conditions or in the absence of DMC with methyl benzylcar-
bamate as the starting material.
2
,6-positions can provide the corresponding products in excel-
lent yields, 91% and 90% respectively (Table 2, entries 2,3).
Either electron-donating or electron-withdrawing substituents
at the para position, good yields of the desired esters can be
isolated in general (Table 2, entries 4-7). In addition to naph-
thalen-1-ylmethanamine, pyridin-2-ylmethanamine and thio-
phen-2-ylmethanamine can be successfully carbonylated under
our standard conditions as well (Table 2, entries 9 and 10).
Additionally, secondary benzylic amines can also be applied
(
Table 2, entries 11-19). Various N-methyl benzyl amines
were selectively transformed and provided the desired prod-
ucts in moderate to good yields. And other types of N-alkyl
substituted benzyl amines are proven to be suitable substrates
as well. In the case of dibenzylamine, both of the benzylic
groups can be activated and utilized (Table 2, entry 19).
Moreover, tertiary substituted benzyl amine can be applied
without any problem. 80% of methyl 2-phenylacetate was
produced from N,N-dimethyl benzyl amine under our standard
conditions (Table 2, entry 20). Ethanol was tested in DMC in
our model system as well, but a mixture of ethyl 2-
phenylacetate and methyl 2-phenylacetate were obtained. The
methanol for methyl 2-phenylacetate was from the reaction
between ethanol and DMC. This problem can be overcome by
using diethyl carbonate as the solvent for ethanol, good yield
of the corresponding ester was produced (Table 2, entry 21).
However, aliphatic amines failed in this system and only the
corresponding ureas could be detected after reacted with
DMC.
Scheme 1. Control experiments.
Table 2. Pd-catalysed carbonylative transformation of benzyl
With all these results in our mind, a possible reaction path-
way is proposed and shown in Scheme 2. Firstly, the benzylic
C-N bond can be activated by palladium catalyst to give the
corresponding organopalladium complex A. Secondary,
acylpalladium intermediate B as the key intermediate will be
produced after the coordination and insertion of CO to the Pd-
C bond of complex A. Finally, the desired ester product will
be eliminated after the nucleophilic attack of MeOH to the
complex B and meanwhile regenerates the active palladium
species for the next cycle. Concerning the roles of DMC,
besides acting as solvent, a part of the DMC might be trans-
[
a]
amines.
Entry
1
Benzyl amines
Products
Yield
90%
2
91%
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