Access to Esters with a Benzylic Quaternary Carbon Center
TABLE 5. Catalysis with Substrates Bearing o- or p-NO2C6H4
Groups
SCHEME 11. Possible Applications of Nitro-Substituted
Compounds
entry
substrate
conditiona
3 (%)b
enantioenriched substrate clarified that enolate re/si face selec-
tion is necessary to achieve asymmetric decarboxylative ally-
lation, and that enantiotopic selection has no effect on enanti-
oselectivity, at least under these reaction conditions. A previously
reported catalytic system in which allylic moieties return to their
parent carbanions was at first considered a likely possibility,
invoking the possible predominance of enantiotopic selection
for diallyl malonates derivatives, but the results obtained from
a scrambling experiment with 1e and 1i revealed that the
observed “boomerang phenomenon” was likely to be due to
the difference in the ground-state structures of the two cationic
(allylic)palladium complexes, which affects their anion release
rates. The introduction of nitro groups on the phenyl ring of
the substrate resulted in effective stabilization of the carboxylate
anion species, even in catalysis using electron-deficient phos-
phite ligands.
1
2
3
4
1k
1k
1l
A
B
A
B
88
97
80
90
1l
a Condition A: Pd(PPh3)4 (2 mol %), substrate (0.5 mmol), CH2Cl2 (1
mL). Condition B: Pd2(dba)3‚CHCl3 (1 mol %), P(OPh)3 (8 mol %),
substrate (0.5 mmol), CH2Cl2 (1 mL). b Isolated yield.
to proceed with less active ligands. If the carboxylate anions
could be made sufficiently stable to leave behind an unstable
cationic complex, for example, π-allylpalladium(phosphite)n, the
use of a variety of chiral phosphite ligands would be possible.
For this purpose, 1k and 1l, which were expected to generate
stabilized carboxylate anions due to the electron-withdrawing
effect of their nitro groups, were separately prepared and applied
in the catalytic reaction. The results are summarized in Table
5. As we expected, the reactions took place smoothly even with
P(OPh)3 to afford the corresponding products 3k and 3l,
respectively. Without P(OPh)3, no reaction took place using 1l
under the same conditions, even after 3 h. The nitro group was
found to be so effective that compound 8 (7%), presumably
derived from double decarboxylative allylation of 1l, was
detected (entry 3). In contrast, the compound 7 was not detected
by TLC analysis (entry 1).
These results seemed promising, not only because a variety
of chiral phosphite and phosphoramidite ligands could be applied
in the catalysis, but also because the nitro groups could be
transformed into Ar-NH2 groups, which would lead to the
synthesis of useful compounds such as AG-115 and oxindole
derivatives16 (Scheme 11). Investigation of the application of
1k and 1l to asymmetric catalysis using a variety of chiral
phosphite/phosphoramidite ligands is now in progress.
Experimental Section
General Procedure for the Preparation of Diallyl 2-Phenyl-
malonate (1f). Phenylmalonic acid (15 g, 83 mmol), allyl alcohol
(45 mL, 660 mmol), and p-toluenesulfonic acid monohydrate (1.7
g, 9.0 mmol) were dissolved in benzene (800 mL), and H2O was
azeotropically removed. After the reaction was complete, the
apparatus was cooled to ambient temperature. The benzene solution
was washed with saturated aqueous NaHCO3 and saturated aqueous
NaCl and was dried over anhydrous Na2SO4. A yellow oil remained
after concentration and was purified by silica gel column chroma-
tography (hexane/AcOEt ) 4:1), affording 1f (colorless oil) in 94%
1
yield (20 g). H NMR (CDCl3, 300 MHz) δ 4.62 (ddd, A of AB
system, J ) 15, 5.7, 1.5, 2H), 4.67 (ddd, B of AB system, J ) 15,
5.7, 1.5, 2H), 4.69 (s, 1H), 5.21 (dq, J ) 10.5, 1.5, 2H), 5.27 (dq,
J ) 17.1, 1.5, 2H), 5.87 (ddt, J ) 17.1, 10.5, 5.7, 2H), 7.32-7.43
(m, 5H); 13C NMR (CDCl3, 75 MHz) δ 57.8, 66.3, 118.6, 128.2,
128.5, 129.2, 131.2, 131.3, 132.4, 167.5; HRMS (FAB+) calcd for
C15H17O4 261.1127 [M + H]+, found 261.1127.
In summary, we found that the presence of an aryl group at
the R-position of diallyl malonates enabled fast palladium-
catalyzed decarboxylative allylation even at room temperature,
affording esters with an all-carbon benzylic quaternary center.
The catalyst was found to be recyclable when [bdmim][BF4]
was used as a reaction medium. Investigation of the reaction
using a tetradeuterated substrate revealed some details of the
catalytic mechanism. The use of an enzymatically synthesized
General Procedure for the Preparation of Diallyl 2-Alkyl-2-
phenylmalonate (1). A variety of disubstituted malonates 1 except
for 1f were prepared by the conventional method for malonic ester
synthesis (1b from ethyl iodide, 1c from benzyl bromide, 1d from
methyl acrylate, 1e from acrylonitrile as nucleophiles; 1g was
prepared by the same method using diallyl 2-methylmalonate).
General Procedure for the Preparation of Diallyl 2-Methyl-
2-phenylmalonate (1a). Compound 1f (8.0 g, 31 mmol) in
anhydrous THF (80 mL) was added dropwise to NaH (1.1 g, 45
mmol) dissolved in ice-cooled anhydrous THF (80 mL). After the
evolution of H2 gas was complete, the apparatus was warmed to
ambient temperature. To the reaction mixture was slowly added
methyl iodide (4.5 mL, 72 mmol). The resulting mixture was stirred
at 60 °C overnight. After the apparatus was cooled to ambient
temperature, the reaction was quenched by adding 1 M aqueous
HCl and was extracted with hexane. The collected organic layers
were washed with dilute aqueous Na2S2O3 saturated aqueous NaCl
and was dried over anhydrous Na2SO4. A yellow oil remained after
(15) (a) Vincent, M. J.; Greco, F.; Nicholson, R. I.; Paul, A.; Griffiths,
P. C.; Duncan, R. Angew. Chem., Int. Ed. 2005, 44, 4061. (b) Chang,
M.-y.; Chang, B.-r.; Tai, H.-m.; Chang, N.-c. Tetrahedron Lett. 2000, 41,
10273. (c) Bushell, S. M.; Crump, J. P.; Lawrence, N. J. Pineau, G.
Tetrahedron 1998, 54, 2269. (d) Fadel, A.; Garcia-argote, S. Tetrahedron:
Asymmetry 1996, 7, 1159.
(16) (a) Kawasaki, T.; Ogawa, A.; Terashima, R.; Saheki, T.; Ban, N.;
Sekiguchi, H.; Sakaguchi, K.-e.; Sakamoto, M. J. Org. Chem. 2005, 70,
2957. (b) Huang, A.; Kodanko, J. J.; Overman, L. E. J. Am. Chem. Soc.
2004, 126, 14043. (c) Morales-R´ıos, M. S.; Santos-Sa´nchez, N. F.; Mora-
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9b-d.
J. Org. Chem, Vol. 72, No. 5, 2007 1657