1
1
propanoic acids. In most of the cases high conversions and
reaction rates are observed with more than 95% selectivity
to the desired 2-arylpropanoic acids. The only traces of
detected byproduct are the isomeric 3-arylpropanoic acids.
In the case of less hindered terminal olefins very high
reaction rates and selectivity were obtained with almost
complete conversion. The reaction rate was the highest for
styrene (1a). When the reactivities of 4-substituted styrenes
are compared, slight enhancement in the reaction rate can
be seen for 4-methyl (1b) and 4-tert-butyl (1c) styrenes,
which have a positive inductive effect compared to 4-chloro-
(1e) and 4-bromostyrenes (1f). However, 1e and 1f showed
very high selectivity for the 2-arylpropanoic acids. With
hindered terminal olefins such as R-methylstyrene (1g),
reaction rates were very low, with poor selectivity for
(
11) Typical Procedure for the Preparation of 2-Arylpropanoic Acids
by Carbonylation of Vinyl Aromatics. The carbonylation reactions were
carried out in a Parr Hastelloy C autoclave (50 mL). In a typical reaction,
the substrate 1 (28.1 mmol), PdCl2(PPh3)2 (0.056 mmol), LiCl/TsOH (5.6
mmol), water (66 mmol), and the methyl ethyl ketone (21 mL) were charged
to the autoclave. The contents were flushed a few times with nitrogen
followed by carbon monoxide and heated to the desired temperature. After
the temperature was attained (115 °C), the autoclave was pressurized with
CO (5.4 MPa) and the reaction was started by agitation (1000 rpm). To
maintain the pressure in the reactor, CO was fed through a constant-pressure
regulator from a reservoir vessel. The pressure drop in the reservoir vessel
was recorded by means of a pressure transducer. The reaction was continued
until the CO absorption was stopped. After the reaction, the autoclave was
cooled to room temperature, CO-depressurized, and flushed with nitrogen
and the reaction mixture removed. The analysis of the liquid samples was
carried out using a gas chromatograph (HP 5890) using a HP-FFAP capillary
column. To isolate the product, the solvent was evaporated, the residue
was dissolved in toluene and was filtered to remove the precipitate. From
the filtrate, the product was isolated by extraction with aqueous NaHCO3
followed by acidification, re-extraction using dichloromethane, and evapora-
tion. The products were further confirmed by IR and NMR. 2a: IR (neat)
2-methyl-2-phenylpropanoic acid product (2g). This may be
due to the steric hindrance created at the metal center, and
isomerization can easily take place to decrease the strain due
to steric bulk at the palladium center. Internal olefins such
as â-methylstyrene (1h) also showed lower reactivity, but
the regioselectivity was comparatively higher than that of
R-substituted terminal olefins.
3 4 2
Palladium(0) complexes such as Pd(PPh ) and Pd(dba)
can also be used as the catalyst precursors. Since water also
is a reactant, solvents which homogenize the reactants as
well as catalyst components are required. We found that in
this case methyl ethyl ketone (MEK) is convenient to work
with, even though other polar solvents such as NMP and
DMF also give similar results. In toluene, the reaction
proceeds very slowly, but the selectivity remained almost
the same.
-
1 1
3
500-2500 (bs), 1695 (s) cm ; H NMR (300 MHz, CDCl3) δ 7.258 (m,
4
H), 3.725 (q, 4H), 1.5 (d, 3H). 2b: IR (neat) 3000-2600 (bs), 1700 (s)
-
1 1
cm ; H NMR (CDCl3) δ 11.409 (bs, 1H), 7.321 (d, 2H), 7.234 (d, 2H),
3
1
2
2
3
.8 (q, 1H), 2.425 (s, 3H), 1.598 (d, 3H). 2c: IR (CHCl3) 3100-2600 (bs),
-1 1
700(s) cm ; H NMR (CDCl3) δ 9.77 (bs, 1H), 7.353 (d, 2H), 7.254 (d,
H), 3.716 (q, 1H), 1.501 (d, 3H), 1.308 (s, 9H). 2d: IR (CHCl3) 3400-
-
1 1
800 (bs), 1705 (s) cm ; H NMR (CDCl3) δ 7.3 (d, 2H), 7.125 (d, 2H),
.75 (q, 1H), 2.5 (d, 3H), 1.85 (m, 1H), 1.515 (d, 2H) 0.945 (d, 6H). 2e:
In conclusion, we have demonstrated a convenient and
regioselective method for the synthesis of a variety of
2-arylpropanoic acids from the corresponding vinyl aromatic
compounds through carbonylation. Up to 99.8% selectivity
is obtained for nonhindered terminal olefins with very high
-
1 1
IR (neat) 3200-2500 (bs), 1695 (bs) cm ; H NMR (CDCl3) δ 9.83 (bs,
H), 7.285 (d, 2H), 7.231 (d, 2H), 3.699 (q, 1H), 1.48 (d, 3H). 2f: IR
CHCl3) 3300-2600 (bs), 1700(s) cm ; H NMR (CDCl3) δ 10.823 (bs,
H), 7.445 (d, 2H), 7.187 (d, 2H), 3.689 (q, 1H), 1.486 (d, 3H). 2g: IR
1
(
-
1 1
1
(
-
1 1
neat) 3500-2600 (bs), 1698 (s) cm ; H NMR (CDCl3) δ 11.156 (bs,
1
1
5
3
1
H), 7.604-7.278 (m, 5H), 1.706 (s, 6H). 2h: IR (neat) 3500-2600 (bs),
-1 1
-1
700 (bs) cm ; H NMR (CDCl3) δ 11.245 (bs, 1H), 7.428-7.253 (m,
H), 3.508 (t, 1H)2.159 (m, 2H), 0.952 (t, 3H). 2i: IR (CHCl3) 3500-
turnover frequencies ranging from 1000 to 2250 h .
1
Comparatively high reaction rates were also obtained for
carbonylation of hindered olefins.
000 (bs), 1710 (s); H NMR (CDCl3), δ 7.67-7.05 (m, 6H), 5.075 (q,
H), 3.865 (s, 3H), 1.575 (d, 3H).
(
12) Francalanci, F.; Gardano, A.; Foa, M. J. Organomet. Chem. 1985,
82, 277.
13) Alper, H.; Woell, J. B.; Despeyroux, B.; Smith, D. J. H. J. Org.
Chem. 1993, 58, 4739.
2
Acknowledgment. A.S. and S.J. thank the CSIR (Council
of Scientific and Industrial Research) of India for a research
fellowship.
(
(
(
14) Andrea, G.; Franco, F.; Marco, F. U.S. Patent 4 536 595.
15) Baird, J. M.; Kern, J. R.; Lee, G. R.; Morgans, D. J., Jr.; Sparacino,
M. L. J. Org. Chem. 1991, 56, 1928.
OL990665+
Org. Lett., Vol. 1, No. 3, 1999
461