Reversal of Enantioselectivity in the Hydroformylation of Styrene with [2S,4S-BDPP]Pt(SnCl3)Cl at High Temperature Arises from a Change in the Enantioselective-Determining Step

Article abstract of DOI:10.1021/ja0318479

Deuterioformylation of styrene catalyzed by [(2S,4S)-BDPP]Pt(SnCl ₃)Cl at 39 °C gave 3-phenylpropanal (3) and 2-phenylpropanal (2) (n:i = 1.8, 71% ee (S)-2) with deuterium only β to the aldehyde carbonyl and in the formyl group. Small amounts o

Full text of DOI:10.1021/ja0318479

Published on Web 04/09/2004
Reversal of Enantioselectivity in the Hydroformylation of Styrene
with [2S,4S-BDPP]Pt(SnCl3)Cl at High Temperature Arises
from a Change in the Enantioselective-Determining Step
Charles P. Casey,* Susie C. Martins, and Maureen A. Fagan†
Contribution from the Department of Chemistry, UniVersity of Wisconsin-Madison,
Madison, Wisconsin 53706
Received December 19, 2003; E-mail: casey@chem.wisc.edu
Abstract: Deuterioformylation of styrene catalyzed by [(2S,4S)-BDPP]Pt(SnCl3)Cl at 39 °C gave 3-phe-
nylpropanal (3) and 2-phenylpropanal (2) (n:i ) 1.8, 71% ee (S)-2) with deuterium only â to the aldehyde
carbonyl and in the formyl group. Small amounts of deuterium were also found in the internal (2.8%), cis
terminal (1.4%), and trans terminal (1.3%) vinyl positions of the recovered styrene. Deuterioformylation of
styrene at 98 °C gave 3- (3) and 2-phenylpropanal (2) (n:i ) 2.3, 10% ee (R)-2) with deuterium both R and
â to the aldehyde carbonyl and in the formyl group. Deuterium was also found in the internal (20%), cis
terminal (12%), and trans terminal (12%) vinyl positions of the recovered styrene. These deuterioformylation
results establish that platinum hydride addition to styrene is largely irreversible at 39 °C but reversible at
98 °C. Hydroformylation of (E)- and (Z)-â-deuteriostyrene at 40 °C, followed by oxidation of the aldehydes
to acids, and subsequent derivitization to the (S)-mandelate esters confirmed that 84% of 2-phenylpropanal
(2) arises from platinum hydride addition to the si-face of styrene, while 73% of 3-phenylpropanal (3) arises
from platinum hydride addition to the re-face of styrene. At 100 °C, the effect of variable H2 and CO pressure
on n:i, % ee, and TOF of hydroformylation of styrene was investigated. The results are consistent with
enantioselectivity not being fully determined until the final hydrogenolysis of a platinum acyl intermediate.
Introduction
how regioselectivity and enantioselectivity are being controlled.
The factors which control selectivity are clearly subtle and vary
Asymmetric hydroformylation has great utility in the synthesis
of optically active substrates.1 Styrene and its derivatives are
important substrates for hydroformylation because oxidation of
the resulting optically active aldehydes to 2-arylpropionic acids
yields pharmacologically active, anti-inflammatory analgesics
such as ibuprofen, ketoprofen, and naproxen.2 A number of
interesting systems for regio- and enantioselective styrene
hydroformylation have been developed.3-6 While excellent
progress has been made in finding better catalytic systems, there
remains a lack of a fundamental understanding of when and
from one system to another.
Kolla´r reported a very interesting Pt-catalyzed hydroformy-
lation of styrene in which a change from S- to R-enantioselec-
tivity was seen as a function of temperature: catalysis by
[(2S,4S)-BDPP]Pt(SnCl3)Cl [BDPP ) 2,4-bis(diphenylphos-
phino)pentane] gave the branched aldehyde 2 with 64% ee S at
40 °C but 17% ee R at 100 °C.7,8 This highlights the complexity
in the mechanism of styrene enantioselective hydroformylation.
While Kolla´r7 proposed that the reversal of enantioselectivity
might be due to a temperature-dependent change in the
conformation of the catalyst’s six-membered chelate ring,9 we
thought it was more likely that the step in which enantioselec-
tivity is set changed with temperature. According to the proposed
mechanism for platinum-catalyzed hydroformylation (Scheme
1),10,11 the regio- and stereochemistry of the aldehyde products
† Present address: Department of Chemistry, Smith College, Northamp-
ton, MA 01063.
(1) For recent reviews, see: (a) Bohnen, H.; Cornils, B. AdV. Catal. 2002, 47,
1. (b) Breit, B.; Seiche, W. Synthesis 2001, 1, 1. (c) Eilbracht, P.; Ba¨rfacker,
L.; Buss, C.; Hollmann, C.; Kitsos-Rzychon, B. E.; Kranemann, C. L.;
Rische, T.; Roggenbuck, R.; Schmidt, A. Chem. ReV. 1999, 99, 3329. (d)
Beller, M.; Cornils, B.; Frohning, C. D.; Kohlpaintner, C. W. J. Mol. Catal.
1995, 104, 17. (e) Agbossou, F.; Carpentier, J. F.; Mortreux, A. Chem.
ReV. 1995, 95, 2485. (f) Gladiali, S.; Bayon, J. C.; Claver, C. Tetrahe-
dron: Asymmetry 1995, 6, 1453. (g) Botteghi, C.; Paganelli, S.; Schoinato,
A.; Marchetti, M. Chirality 1991, 3, 355. (h) Consiglio, G.; Pino, P. Top.
Curr. Chem. 1982, 105, 77.
(2) (a) Nugent, W. A.; RajanBabu, T. V.; Burk, M. J. Science 1993, 259, 479.
(b) Rieu, J.-P.; Boucherle, A.; Cousse, H.; Mouzin, G. Tetrahedron 1986,
42, 4095. (c) Harrison, I. T.; Lewis, B.; Nelson, P.; Rooks, W.; Roxzkowski,
A.; Tomolonis, A.; Fried, J. H. J. Med. Chem. 1970, 13, 203.
(3) Babin, J. E.; Whiteker, G. T. (Union Carbide Chemicals and Plastics
Technology Corp., USA). US 5360938 A, 1994.
(7) Kolla´r, L.; Bakos, J.; To´th, I.; Heil, B. J. Organomet. Chem. 1988, 350,
277.
(8) Similar reversals of enantioselectivity upon increasing the temperature in
the hydroformylation of styrene have been seen with PtCl(SnCl3)BINAP
[BINAP ) 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl] and PtCl(SnCl3)-
DIOP [DIOP ) 2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphos-
phino)butane]. (a) Kolla´r, L.; Sa´ndor, P.; Szalontai, G. J. Mol. Catal. 1991,
67, 191. (b) Haelg, P.; Consiglio, G.; Pino, P. J. Organomet. Chem. 1985,
296, 281.
(9) Bosnich reported that chelating diphosphines such as 2,4-bis(diphenylphos-
phino)pentane and 1,3-bis(diphenylphosphino)butane can adopt various
conformations. They attribute the generation of an achiral ligand conforma-
tion in the hydrogenation of amino acids to reduced enantioselectivity.
MacNeil, P. A.; Roberts, N. K.; Bosnich, B. J. Am. Chem. Soc. 1981, 103,
2273.
(4) Buisman, G. J. H.; Kramer, P. C. J.; van Leeuwen, P. W. N. M.
Tetrahedron: Asymmetry 1993, 4, 1625.
(5) RajanBabu, T. V.; Ayers, T. A. Tetrahedron Lett. 1994, 35, 4295.
(6) Sakai, N.; Mano, S.; Nozaki, K.; Takaya, H. J. Am. Chem. Soc. 1993, 115,
7033.
9
10.1021/ja0318479 CCC: $27.50 © 2004 American Chemical Society
J. AM. CHEM. SOC. 2004, 126, 5585-5592
5585

A R T I C L E S
Casey et al.
Scheme 1. Simplified Mechanism for Styrene Hydroformylation
with [2S,4S-BDPP]Pt(SnCl3)Cl Catalyst
followed by irreversible alkyl migration to CO to form a
platinum acyl complex, or (4) reversible platinum acyl formation
followed by irreversible platinum acyl hydrogenolysis to yield
the aldehyde and regenerate the active platinum hydride, as
shown in Scheme 1.
Here, we report deuterioformylation studies and the CO and
H2 pressure dependence of enantioselectivity which show that
at low temperature, enantioselectivity is set by largely irrevers-
ible platinum hydride addition to styrene, but at high temper-
ature, platinum hydride addition is reversible and enantioselec-
tivity is set by a combination of partially reversible alkyl
migration to CO and hydrogenolysis of the platinum acyl
intermediate.
Experimental Section
may be set at any one of four stages: (1) irreversible alkene
coordination to platinum, (2) reversible alkene coordination
followed by irreversible platinum hydride addition to form a
platinum alkyl complex, (3) reversible platinum alkyl formation
Hydroformylation of Styrene at Variable Pressures of H2 and
CO. Hydroformylations were performed in a 25 mL stainless steel Parr
reactor equipped with a magnetic drive stirrer, a Parr 4842 thermo-
couple, and a ReactIR SiComp cell. Each hydroformylation experiment
was performed using octane (0.1 g; 0.875 mmol) as an internal standard
for GC analysis. The reactor containing catalyst 1 (20 mg; 0.022 mmol),
toluene (6.0 mL), and octane was sealed under 1 atm of N2. The reactor
was then heated to the appropriate temperature, and then pressurized
with the respective pressures of CO and H2. Styrene (1.50 g; 14.4 mmol)
was then added via a stainless steel addition funnel by overpressurizing
with N2. Aldehyde formation was monitored at 1730 cm-1 using a ASI
ReactIR 1000. When it appeared that the absorbance of the aldehyde
leveled out, the reaction was stopped; the reactor was slowly vented
and then cooled to room temperature. The average pressure loss during
the reactions was ∼250 psi of synthesis gas. The sample was then
analyzed by GC and 1H NMR spectroscopy. Gas chromatography was
performed using a Supelco â-Dex (â-cyclodextrin) 250 chiral capillary
column on a Hewlett-Packard 5890A gas chromatograph connected to
an HP3390A integrator. The GC flow rate was set to 75 mL/min N2,
an initial temperature of 100 °C (13 min) followed by ramping 30 °C/
min to 210 °C. Typical retention times were as follows: 2.20 min
octane, 2.39 min toluene, 3.08 min ethylbenzene, 3.58 min styrene,
12.48 min (R)-2-phenylpropanal, 12.70 min (S)-2-phenylpropanal, and
15.24 min 3-phenylpropanal. The response factors (calculated by
correlating the moles of internal standard to its corresponding peak
area) for ethylbenzene (1.15), styrene (1.06), 2-phenylpropanal (1.02),
and 3-phenylpropanal (1.07) were calibrated relative to octane using
standards of commercial samples.
(10) The exact coordination environments of the platinum hydride, alkyl, and
acyl complexes are unknown.
(11) References for the use of Pt-SnCl2 catalysts in hydroformylation, see: (a)
Fernandez, D.; Garcia-Seijo, M. I.; Kegl, T.; Petocz, G.; Kolla´r, L.; Garcia-
Fernandez, M. E. Inorg. Chem. 2002, 41, 4435. (b) Foca, C. M.; dos Santos,
E. N.; Gusevskaya, E. V. J. Mol. Catal. A 2002, 185, 17. (c) van der Veen,
L. A.; Keevan, P. K.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Dalton
2000, 13, 2105. (d) Gusevskaya, E. V.; dos Santos, E. N.; Augusti, R.;
Dias, A. d. O.; Foca, C. M. J. Mol. Catal. A 2000, 152, 15. (e) Ellis, D.
D.; Harrison, G.; Orpen, A. G.; Phetmung, H.; Pringle, P. G.; deVries, J.
G.; Oevering, H. Dalton 2000, 5, 671. (f) van der Veen, L. A.; Keevan, P.
K.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Chem. Commun. 2000, 5,
333. (g) Meessen, P.; Vogt, D.; Keim, W. J. Organomet. Chem. 1998, 551,
165. (h) Gladiali, S.; Fabbri, D.; Kolla´r, L. J. Organomet. Chem. 1995,
491, 91. (i) Ancillotti, F.; Lami, M.; Marchionna, M. J. Mol. Catal. 1991,
66, 37. (j) Consiglio, G.; Nefkens, S. C. A.; Borer, A. Organometallics
1991, 10, 2046. (k) Ancillotti, F.; Lami, M.; Marchionna, M. J. Mol. Catal.
1990, 63, 15. (l) Muller, G.; Sainz, D.; Sales, J. J. Mol. Catal. 1990, 63,
173. (m) Consiglio, G.; Nefkens, S. C. A. Tetrahedron: Asymmetry 1990,
1, 417. (n) Ancillotti, F.; Lami, M.; Marchionna, M. J. Mol. Catal. 1990,
58, 331. (o) Kolla´r, L.; Bakos, J.; Heil, B.; Sandor, P.; Szalontai, G. J.
Organomet. Chem. 1990, 385, 147. (p) Ancillotti, F.; Lami, M.; Marchionna,
M. J. Mol. Catal. 1990, 58, 345. (q) Scrivanti, A.; Paganelli, S.; Matteoli,
U.; Botteghi, C. J. Organomet. Chem. 1990, 385, 439. (r) Mutez, S.;
Paumard, E.; Morteux, A.; Petit, F. Tetrahedron Lett. 1989, 30, 5759. (s)
Kolla´r, L.; Consiglio, G.; Pino, P. J. Organomet. Chem. 1987, 330, 305.
(t) Moretti, G.; Botteghi, C.; Toniolo, L. J. Mol. Catal. 1987, 39, 177. (u)
Consiglio, G.; Morandini, F.; Scalone, M.; Pino, P. J. Organomet. Chem.
1985, 279, 193. (v) Clark, H. C.; Jain, V. K.; Rao, G. S. J. Organomet.
Chem. 1985, 279, 181. (w) Cavinato, G.; Toniolo, L. J. Organomet. Chem.
1983, 241, 275. (x) Tang, S.; Kim, L. J. Mol. Catal. 1982, 14, 231. (y)
Hayashi, T.; Kawabata, Y.; Isoyama, T.; Ogata, I. Bull. Chem. Soc. Jpn.
1981, 54, 3438. (z) Clark, H. C.; Davies, J. A. J. Organomet. Chem. 1981,
213, 503. (aa) Kawabata, Y.; Hayashi, T.; Ogata, I. J. Chem. Soc., Chem.
Commun. 1979, 10, 462. (ab) Consiglio, G.; Pino, P. HelV. Chim. Acta
1976, 59, 642 and references therein. For references specifically dealing
with the study of reaction intermediates in the hydroformylation of Pt-
SnCl2 catalysts, see: (a) Scrivanti, A.; Zeggio, S.; Beghetto, V.; Matteoli,
U. J. Mol. Catal. A 1995, 101, 217. (b) Cavinato, G.; Munno, G. De; Lami,
M.; Marchionna, M.; Toniolo, L.; Viterbo, D. J. Organomet. Chem. 1994,
466, 277. (c) Gomez, M.; Muller, G.; Sainz, D.; Sales, J.; Solans, X.
Organometallics 1991, 10, 4036. (d) Graziani, R.; Cavinato, G.; Casellato,
U.; Toniolo, L. J. Organomet. Chem. 1988, 353, 125. (e) Scrivanti, A.;
Botteghi, C.; Toniolo, L.; Berton, A. J. Organomet. Chem. 1988, 344, 261.
(f) Scrivanti, A.; Berton, A.; Toniolo, L.; Botteghi, C. J. Organomet. Chem.
1986, 314, 369. (g) Scrivanti, A.; Cavinato, G.; Toniolo, L.; Botteghi, C.
J. Organomet. Chem. 1985, 286, 115. (h) Bardi, R.; Piazzesi, A. M.;
Cavinato, G.; Cavoli, P.; Toniolo, L. J. Organomet. Chem. 1982, 224, 407
and references therein. For references with the role of SnCl2 in Pt-SnCl2
hydroformylation catalysts, see: (a) Rocha, W. R.; De Almeida, W. B.
Int. J. Quantum Chem. 1997, 65, 643. (b) Kolla´r, L.; Kegl, T.; Bakos, J. J.
Organomet. Chem. 1993, 453, 155. (c) Kolla´r, K.; Sandor, P.; Szalontai,
G.; Heil, B. J. Organomet. Chem. 1990, 393, 153. (d) Ruegg, H. J.;
Pregosin, P. S.; Scrivanti, A.; Toniolo, L.; Botteghi, C. J. Organomet. Chem.
1986, 316, 233. (e) Anderson, G. K.; Clark, H. C.; Davies, J. A. Inorg.
Chem. 1983, 22, 427. (f) Anderson, G. K.; Clark, H. C.; Davies, J. A.
Inorg. Chem. 1983, 22, 434. (g) Anderson, G. K.; Billard, C.; Clark, H.
C.; Davies, J. A.; Wong, C. S. Inorg. Chem. 1983, 22, 439 and references
therein. For studies of CO effect on Pt-SnCl2 hydroformylation catalysts,
see: (a) To´th, I.; Kegl, T.; Elsevier, C. J.; Kolla´r, L. Inorg. Chem. 1994,
33, 5708. (b) Goel, A. B.; Goel, S. Inorg. Chim. Acta 1983, 77, L53 and
references therein. For temperature-dependent studies of Pt-SnCl2 catalysts,
see: To´th, I.; Guo, I.; Hanson, B. E. Organometallics 1993, 12, 848 and
references therein.
Results
Hydroformylation of Styrene at 40 °C. The hydroformy-
lation of styrene catalyzed by [(2S,4S)-BDPP]Pt(SnCl3)Cl (1)
was performed at 40 °C with 1000 psi of an analyzed 1:1
mixture of H2:CO to confirm Kolla´r’s earlier results7 and to
establish a reference for deuterioformylation studies under our
experimental conditions. After 5% conversion of styrene, chiral
GC analysis showed formation of 3-phenylpropanal (3) and
2-phenylpropanal (2) [n:i ) 2.2 and 60% ee (S)-2-phenylpro-
panal (2-(S))]. Under similar reaction conditions, Kolla´r found
n:i ) 1.35 and 64% ee 2-(S)12 (Scheme 2).
Deuterioformylation of Styrene at 39 °C. To determine
whether platinum hydride addition to coordinated styrene is
reversible, a deuterioformylation experiment was conducted. If
hydride addition is irreversible, deuterium will be incorporated
(12) Peak assignments for (R)- and (S)-2-phenylpropanal were confirmed by
oxidation to the respective acids and subsequent derivitization to the (S)-
methyl mandelate esters. Esters (R,S)-4 and (S,S)-4 are distinguishable by
1H NMR spectroscopy.
9
5586 J. AM. CHEM. SOC. VOL. 126, NO. 17, 2004

Hydroformylation of Styrene
A R T I C L E S
Scheme 2
Scheme 3. Deuterioformylation Test for the Reversibility of
â-deuterated aldehydes (Scheme 4, blue). Much more deuterium
shows up in recovered styrene than in the R-position of the
aldehydes, suggesting that when the platinum alkyl reverts to a
platinum hydride styrene complex, the styrene mainly dissociates
from platinum. Styrene complexation to platinum is evidently
rapid and reversible as compared to platinum hydride addition
to the coordinated alkene. The primary deuterated alkyl A is
converted to aldehyde 8.5 times faster than it eliminates to give
R-deuteriostyrene (16.61 mmol/1.96 mmol); taking labeling
statistics into account, this indicates that unlabeled A would be
converted to aldehyde 4.25 (8.5/2) times faster than it eliminates
to styrene. Similarly, the secondary deuterated alkyl B goes on
to aldehyde 4.9 times faster than it eliminates to give â-deu-
teriostyrene [9.23 mmol/(0.98 mmol + 0.91 mmol)];14 this
indicates that unlabeled B would be converted to aldehyde 1.6
(4.9/3) times faster than it eliminates to styrene. At 39 °C,
aldehyde stereochemistry is predominantly set by irreversible
hydride addition which gives a platinum alkyl that is committed
to forming aldehyde. The favored enantiomer is therefore
determined by the difference in the relative rates of formation
of the (R)- and (S)-platinum alkyl intermediates, which in turn
depends on the equilibrium between the two diastereomeric
platinum hydride alkene complexes and their relative rates of
conversion to platinum alkyl complexes.
Hydroformylation of (E)- and (Z)-â-Deuteriostyrene at 39
°C. At 39 °C, platinum hydride preferentially adds to the si-
face of complexed styrene to form the iso-alkyl that is converted
to 2-(S). This was established by analysis of the ratio of
enantiomers of 2-(S) and 2-(R) by chiral GC. An unanswered
question remained: Is the n-aldehyde produced predominantly
by hydride addition to the same or opposite alkene enantioface
as the iso-aldehyde? To address this question, the hydroformy-
lation of (E)-â-deuteriostyrene was carried out and the stereo-
chemistry of the deuterated n-aldehydes was determined.
Hydroformylation of (E)-â-deuteriostyrene with complex 1
at 39 °C under 1200 psi of 1:1 H2:CO for 196 h showed that
93% of the styrene converted to 3 and 2 with n:i ) 1.8 and
68% ee 2-(S). Oxidation of the crude aldehyde products with a
KH2PO4 buffered solution of KMnO4 yielded 84% of 3- and
2-phenylpropanoic acids. Reaction of the acids with methyl (S)-
(+) mandelate [(S)-PhCH(OH)CO2Me], DCC [1,3-dicyclohexyl-
carbodiimide], and catalytic DMAP [4-(dimethylamino)pyridine]
yielded 61% of mandelate esters 4 and 5 (Scheme 5). The
stereochemistry of mandelate esters 5 was previously deter-
mined.15
Platinum Hydride Addition to Styrenea
a Products in boxes require reversible â-hydride elimination.
only â to the aldehyde carbonyl group and in the formyl group.
If hydride addition is reversible, deuterium will be incorporated
both R and â to the aldehyde carbonyl groups and in the
recovered styrene (Scheme 3). For example, platinum deuteride
addition to give a secondary alkyl platinum complex will lead
to incorporation of deuterium only in the â position of
2-phenylpropanal if the addition is irreversible. However, if the
secondary alkyl platinum complex undergoes â-hydride elimina-
tion and subsequently re-adds hydride to form a primary alkyl
platinum complex, deuterium will be incorporated at the R
position of 3-phenylpropanal.
Deuterioformylation of styrene catalyzed by complex 1 was
conducted under 600 psi D2 and 600 psi CO at 39 °C. After
119 h, chiral GC analysis showed that 27% of the styrene had
been converted to 3 and 2 with n:i ) 1.8 and 71% ee 2-(S).13
1
2
For 3 and 2, both H and H NMR spectroscopy showed the
presence of one deuterium â to the carbonyl and one deuterium
in the formyl group. No deuterium was observed in the
R-positions of either aldehyde regioisomer, although as little
as 5% would have been detected by NMR spectroscopy. In the
73% recovered styrene, deuterium was found in the internal
(2.8% D), cis terminal (1.4% D), and trans terminal (1.3% D)
vinyl positions. Thus, styrene reacted to give 87% aldehydes
and 13% deuterated styrene.
These observations provide evidence that platinum deuteride
addition to coordinated styrene is largely irreversible. The
initially generated platinum alkyl is mainly converted to
The mixture of mandelate esters was analyzed by 1H and 2H
NMR spectroscopy. The branched esters were distinguished by
(13) Integrations from 1H and 2H NMR spectroscopy were used to calculate
deuterium incorporation into the aldehydes and recovered styrene. NMR
samples were prepared in CDCl3 or toluene-d8 from a solution of the crude
hydroformylation mixture (2.0 mL) and an internal standard of 1:1 CH2-
Cl2:CD2Cl2 (60 µL).
(14) This calculation is further clarified by Scheme 1 in the Supporting
Information.
9
J. AM. CHEM. SOC. VOL. 126, NO. 17, 2004 5587

A R T I C L E S
Casey et al.
Scheme 4. Relative Rates of Aldehyde Formation As Compared to â-Hydride Elimination at 39 °C (Blue) and at 98 °C (Red)a
a Numbers in parentheses are corrected for labeling statistics.
Scheme 5. Derivitization of Chiral Aldehydes by Conversion to
Mandelate Esters
Scheme 6. Linear and Branched Aldehydes Arise from Hydride
and CO Addition to Opposite Enantiofaces of Styrene
of styrene leads predominantly to a primary alkyl platinum
intermediate and results in n:i selectivity of 8.4, while com-
plexation to the si-face leads mainly to a secondary alkyl
platinum intermediate and n:i selectivity of 0.59.
Analysis of the products from hydroformylation of (Z)-â-
deuteriostyrene led to the same conclusions about the stereo-
chemistry of aldehyde formation.17
Hydroformylation of Styrene at 100 °C. The hydroformy-
lation of styrene catalyzed by 1 was performed at 100 °C with
1000 psi of a 1:1 mixture of H2:CO for comparison with Kolla´r’s
earlier results.7 After 4.5 h, chiral GC analysis showed nearly
complete conversion of styrene and formation of 63.4% 3,
14.1% 2-(R), 11.8% 2-(S), and 10% ethylbenzene from hydro-
genation (Scheme 2, red). The n:i ) 2.4 and 10% ee 2-(R) are
similar to the n:i ) 2.7 and 17% ee 2-(R) reported by Kolla´r
under similar conditions.
Deuterioformylation of Styrene at 98 °C. Deuterioformy-
lation of styrene catalyzed by complex 1 was carried out under
600 psi D2 and 600 psi CO at 98 °C. After 1.6 h, 30% of the
styrene had converted to 3 and 2 with n:i ) 2.3 and 10% ee
2-(R) (Scheme 7). Integrations from 1H and 2H NMR spectros-
copy showed extensive deuterium incorporation into the R- as
well as the â-position of the aldehydes and into all three vinyl
positions of styrene. For 3, 0.12 D was found at the R-position
in addition to 0.80 D at the â-position and 0.89 D in the formyl
group. Similarly for 2, 0.10 D was found at the R-position in
addition to 0.78 D at the â-position and 0.90 D in the formyl
group. In the 67% recovered styrene, deuterium was found in
the internal (0.20 D), cis terminal (0.12 D), and trans terminal
(0.12 D) vinyl positions.
the 1H NMR resonances of the CHCH2D groups which appear
at δ 3.78 (t, 1.0 H, J ) 6.9 Hz) for (R,S)-4 and at δ 3.69 (t, 5.1
H, J ) 6.9 Hz) for (S,S)-4. The diastereomeric excess calculated
from these 1H NMR integrations is 67% de, which is similar to
the 68% ee 2-(S) measured by chiral GC in the hydroformylation
of (E)-â-deuteriostyrene. This demonstrates that racemization
did not occur in the derivitization process. The straight chain
1
esters were distinguished by the H NMR resonances of the
3
CHDCO2R groups which appear at δ 2.57 (tt, 0.7 H, JHH
)
7.4 Hz, 1JHD ) 1.8 Hz) for (S,S)-5 and at δ 2.47 (m, 0.3 H) for
(R,S)-5. This 70:30 ratio of (S,S)-5:(R,S)-5 determined from 1H
NMR spectroscopy was confirmed by H NMR spectroscopy.
2
Simulation of the 2H NMR of CHDCO2R resonances of (R,S)-5
and (S,S)-5 with winDNMR16 gave the relative amounts of the
two diastereomers as 27.3 ( 2% (R,S)-5 and 72.7 ( 2% (S,S)-
5.
Scheme 6 summarizes the stereochemistry of aldehyde
formation. The n-aldehyde constitutes 64.5% of the aldehydes,
and 73% of it is formed by platinum hydride addition to the
re-face of styrene. In contrast, the iso-aldehyde constitutes
35.5% of the aldehydes, and 84% of it is formed by platinum
hydride addition to the si-face of styrene. It is interesting that
nearly equal amounts of aldehydes arise from the si- (47.5%)
and re-faces (52.5%) of styrene. Complexation to the re-face
The observation of deuterium in the R-positions of 3, 2, and
in recovered styrene provides evidence for extensive reversible
platinum hydride addition to styrene at 98 °C. The analysis in
Scheme 7 shows that the initial primary deuterated alkyl
(15) (a) Parker, D. J. Chem. Soc., Perkin Trans. 2 1983, 83. (b) Giesel, H.;
Machacek, G.; Bayerl, J.; Simon, H. FEBS Lett. 1981, 123, 107. (c) Bartl,
K.; Cavalar, C.; Krebs, T.; Ripp, E.; Re´tey, J.; Hull, W. E.; Gu¨nther, H.;
Simon, H. Eur. J. Biochem. 1977, 72, 247. (d) Hashimoto, H.; Rambeck,
B.; Gu¨nther, H.; Mannschreck, A.; Simon, H. Hoppe-Seyler’s Z. Physiol.
Chem. 1975, 356, 1203. (e) Simon, H.; Rambeck, B.; Hashimoto, H.;
Gu¨nther, H.; Nohynek, G.; Neumann, H. Angew. Chem., Int. Ed. 1974, 13,
608.
(17) A mixture of (Z)-â-deuteriostyrene, styrene, phenylacetylene-d1, and
complex 1 was placed under 1200 psi 1:1 H2:CO and reacted at 39 °C for
192 h. GC analysis showed 89% conversion to aldehydes, n:i ) 1.8, and
2
63% ee (S)-2-phenylpropanal. Simulation of the H NMR spectrum of 2-
and 3-phenylpropanal-derived (S)-methyl mandelate esters gave 65.7%
(R,S)-5 and 34.3% (S,S)-5.
(16) Reich, H. J. J. Chem. Educ. 1995, 72, 1086.
9
5588 J. AM. CHEM. SOC. VOL. 126, NO. 17, 2004

Hydroformylation of Styrene
A R T I C L E S
Scheme 7. Deuterioformylation of Styrene at 98 °C
Table 1. CO Pressure Dependence on the Hydroformylation of
Styrene at 100 °C
CO (psi)
H (psi)
2
n:i
ee
ethylbenzene
TOF (h-1
)
200
400
600
800
1000
400
400
400
400
400
3.18
3.20
3.26
3.13
3.35
22% R
19% R
21% R
18% R
20% R
41%
21%
12%
10%
7%
25
142
94
107
68
with the greater propensity of the secondary alkyl platinum to
â-hydride eliminate.
A third deuterioformylation of styrene was performed at 600
psi D2 and 600 psi CO at 96 °C in which aliquots were removed
from the reaction mixture every 30 min. 1H and 2H NMR
spectroscopy confirmed that the hydrogen content of the formyl
groups gradually escalated over the course of the reaction. After
1 h and 10% conversion of styrene, no hydrogen was seen in
the formyl groups, but after 2 h and 37% conversion, 12-14%
hydrogen was seen in the formyl groups.
The significant hydrogen distribution in the formyl groups
originates from cleavage of the platinum acyl intermediates by
reaction with HD rather than D2. Extensive exchange between
styrene and D2 provides a source of HD. HD can arise from
reversible platinum alkyl formation, followed by exchange of
the platinum hydride with D2.
Because platinum hydride addition to styrene is mainly
reversible at high temperature, the regio- and enantioselectivity
of aldehyde formation must arise during a step later in the
catalytic cycle, either acyl formation or acyl hydrogenolysis.
At 39 °C, the S-alkyl platinum intermediate is selectively formed
and is mainly converted to 2-(S). At 98 °C, the formation of
the alkyl platinum intermediates is largely reversible, and the
R-alkyl platinum intermediate is converted selectively to an
enantiomeric excess of 2-(R).
Hydroformylation of Styrene at 96 °C under 1275 psi CO
and 125 psi H2. If alkyl migration to CO is the step at which
enantioselectivity is set and if it is CO-pressure dependent, then
an increase in CO pressure should increase the rate of alkyl
migration to CO relative to â-hydride elimination and alter the
enantioselectivity to favor the formation of more 2-(S). To test
this hypothesis, we studied the hydroformylation of styrene at
higher CO pressure. To maximize the CO pressure and stay
within the convenient limits of tank pressure, the hydroformy-
lation of styrene was studied under the following conditions.
A solution of styrene and 1 in toluene was placed under 1275
psi CO and 125 psi H2 and heated to 96 °C for 24 h. Chiral GC
analysis showed 46% conversion to aldehydes and, unexpect-
edly, an increase to 21% ee 2-(R) and an increase in the n:i
ratio to 4.3. Because both CO and H2 pressure were changed
simultaneously, it was not clear whether CO pressure, H2
pressure, or both were contributing to a change in the reaction’s
selectivity. A systematic study of both CO and H2 pressure
dependence on enantioselectivity and n:i was clearly needed.
Hydroformylation of Styrene at 100 °C under Variable
CO Pressure. The hydroformylation of styrene with 1 at 100
°C was performed at constant 400 psi H2 pressure while varying
CO pressure systematically from 200 to 1000 psi (Table 1).
Surprisingly, neither the % ee 2-(R) nor the n:i ratio varied
appreciably as the CO pressure was changed. However, an
increase in CO pressure was accompanied by a decrease in the
amount of styrene hydrogenation. The turnover frequencies
platinum intermediate A is converted to â-deuterated 3-phe-
nylpropanal (15.6 mmol) or to R-deuterated styrene (25.8 mmol
seen); some R-deuterated styrene was also hydroformylated in
situ to give R-deuterated 2-phenylpropanal (0.9 mmol) and
(based on the n:i ratio) additional â-deuterated 3-phenylpropanal
(2.0 mmol). Therefore, the primary deuterated alkyl A eliminates
to give R-deuteriostyrene (25.8 + 0.9 + 2.0 mmol) 1.8 times
faster than it is converted to 3-phenylpropanal (3) (15.6 mmol)
(Scheme 4, red); taking labeling statistics into account, this
indicates that unlabeled A would eliminate to styrene 3.6 (1.8
× 2) times faster than it is converted to aldehyde. Similarly,
the secondary deuterated alkyl B eliminates to give â-deuterio-
styrene (23.2 + 2.4 + 1.0 mmol) 3.9 times faster than it is
converted to 2-phenylpropanal (2) (6.8 mmol); taking labeling
statistics into account, this indicates that unlabeled B would
eliminate to styrene 11.7 (3.9 × 3) times faster than it is
converted to aldehyde.
When a second deuterioformylation of styrene under 600 psi
D2 and 600 psi CO at 96 °C was carried to longer time (4.5 h),
91% of the styrene was converted to aldehydes and the 2%
recovered styrene was almost completely deuterated at the vinyl
positions. Chiral GC analysis showed 3 and 2 with n:i ) 2.5
1
2
and 11% ee 2-(R). H and H NMR spectroscopy showed that
the R positions of 3 and 2 contained 0.58 and 0.37 D,
respectively. The â positions of both aldehydes had more than
one deuterium incorporated: 3 had 1.06 D and 2 had 1.74 D.
The formyl groups had less than one deuterium: 3 and 2 had
1
2
0.69 and 0.75 D, respectively. H and H NMR spectroscopy
of the 2% recovered styrene revealed extensive deuteration of
the internal (0.95 D), cis (0.69 D), and trans (0.75 D) vinyl
hydrogens.
These results require extensive â-hydride elimination from
the initially formed platinum alkyls. Reversibility is so extensive
that recovered styrene is highly deuterated. Deuterioformylation
of deuterium exchanged styrene is responsible for R-deuteration
and is required for incorporation of more than one D at the
â-position. The substantially greater amount of deuterium in
the R-position of 3 (0.58 D) than in 2 (0.37 D) is consistent
9
J. AM. CHEM. SOC. VOL. 126, NO. 17, 2004 5589

A R T I C L E S
Casey et al.
Table 2. H2 Pressure Dependence on the Hydroformylation of
Styrene at 100 °C
Table 3. CO Pressure Dependence on the Hydroformylation of
Styrene at 50 °C
H (psi)
2
CO (psi)
n:i
ee
ethylbenzene
TOF (h-1
)
CO (psi)
H (psi)
2
n:i
ee
ethylbenzene
TOF (h-1
)
200
400
400
400
400
400
400
3.69
3.20
2.54
2.25
1.92
22% R
19% R
15% R
10% R
6% R
20%
21%
21%
21%
24%
44
142
163
201
443
200
400
400
400
400
400
400
1.92
2.12
2.46
2.51
2.55
22% S
40% S
48% S
57% S
57% S
10%
7%
3%
2%
2%
3
5
8
7
7
600
600
800
1000
800
1000
Table 4. H2 Pressure Dependence on the Hydroformylation of
Styrene at 50 °C
(TOF) for aldehyde formation are absolute rates and are
consequently more variable than the n:i ratios and % ee which
are relative rates. No systematic variation in TOF as a function
of CO pressure was noted.
The decrease in % hydrogenation as CO pressure was
increased requires that the transition state for hydrogenation have
one fewer CO than the transition state for hydroformylation.
While the rate of hydroformylation is zero order in CO, the
rate of hydrogenation is inverse order in CO.
H (psi)
2
CO (psi)
n:i
ee
ethylbenzene
TOF (h-1
)
200
400
400
400
400
400
400
3.11
2.12
1.84
1.54
1.46
18% S
40% S
49% S
55% S
60% S
3%
7%
3
5
10
10
10
600
7%
800
1000
9%
12%
converted back to styrene. To determine whether aldehyde
formation is reversible under our reaction conditions, the
deuterioformylation of 4-methylstyrene with complex 1 was
performed in a solution containing 2 and 3. After 4 h at 96 °C
under 600 psi D2 and 600 psi CO, GC analysis revealed that
91% of the 4-methylstyrene was converted to aldehydes. No
Hydroformylation of Styrene at 100 °C under Variable
H2 Pressure. The hydroformylation of styrene with 1 at 100
°C was performed at constant 400 psi CO pressure while varying
H2 pressure systematically from 200 to 1000 psi (Table 2). As
the H2 pressure was increased, the formation of 3 decreased
and the formation of both 2-(S) and 2-(R) increased, although
2-(S) increased more than 2-(R). This resulted in a shift of the
enantiomeric excess to lower % ee 2-(R) and to a decrease in
the n:i ratio. There was no appreciable hydrogen pressure
dependence on the % hydrogenation. The turnover frequency
(TOF) increased at higher hydrogen pressure.
The H2 pressure dependence of the % ee and n:i ratio requires
that enantioselectivity not be fully set until acyl hydrogenolysis.
At higher H2 pressure and 100 °C, the % ee and the n:i ratio
both move toward the values seen at 40 °C where selectivity is
controlled by largely irreversible platinum hydride addition. At
40 °C, there is a greater propensity to form the S-alkyl platinum
intermediate, which is mainly carried on to 2-(S). At 100 °C,
the formation of alkyl platinum intermediates is more reversible
and selectivity is controlled by a later step in the hydroformy-
lation cycle. The preference for 2-(R) under these conditions is
a result of either an equilibrium favoring the (R)-acyl intermedi-
ate or of a more rapid hydrogenolysis of the (R)-acyl intermedi-
ate. The shift to lower % ee 2-(R) at higher H2 pressure is
consistent with having more of the initially formed S-alkyl
platinum intermediate being “locked in” by hydrogenolysis of
an S-acyl platinum intermediate in equilibrium with it. At lower
H2 pressure, more of the S-acyl platinum intermediate has a
chance to revert all the way back to free styrene and then
proceed on to 2-(R).
1
2
styrene was observed by H or H NMR spectroscopy, and no
deuterium was detected by GC/MS in the recovered 2 and 3.19
These results establish that aldehyde formation is irreversible.
Hydroformylation of Styrene at 50 °C under Variable CO
Pressure. While platinum alkyl formation at 40 °C under 600
psi CO and 600 psi H2 was much less reversible than that at
100 °C, some â-hydride elimination occurred to give deuterated
styrene (13% of styrene consumed). In light of the pressure
dependence of % ee and n:i at 100 °C, we investigated their
dependence at lower temperature. To obtain more convenient
rates of hydroformylation, studies were carried out at 50 °C
rather than 40 °C.
The hydroformylation of styrene with 1 at 50 °C was
performed at constant 400 psi H2 pressure while varying CO
pressure systematically from 200 to 1000 psi (Table 3). In
contrast to data at 100 °C where no variation in % ee or the n:i
was seen, the % ee 2-(S) and the n:i ratio increased as CO
pressure was increased at 50 °C. The variation in % ee and n:i
results from an increase in 3, a decrease in 2-(R), and a little
change in 2-(S) as CO pressure is increased. At both 50 and
100 °C, a decrease in CO pressure led to more styrene
hydrogenation but no significant change in TOF.
Hydroformylation of Styrene at 50 °C under Variable H2
Pressure. The hydroformylation of styrene with 1 at 50 °C was
performed at constant 400 psi CO pressure while varying H2
pressure systematically from 200 to 1000 psi (Table 4, Figure
1). The same trends seen at 100 °C were seen at 50 °C. As H2
pressure increased, a shift toward more 2-(S) was seen which
plateaued at about 60% ee 2-(S). The n:i ratio decreased at higher
H2 pressure and plateaued to a value of 1.5. The variation in %
ee and n:i results from an increase in 2-(S) and a proportional
decrease in 3 and 2-(R) as H2 pressure increased. The TOF
increased somewhat at higher H2 pressure. In contrast to results
at 100 °C, an increase in % hydrogenation was seen at higher
H2 pressure.
The constant % hydrogenation along with the increase in TOF
at higher H2 pressure indicates that the rate-determining steps
for both hydrogenation and hydroformylation involve H2.
Deuterioformylation of 4-Methylstyrene in the Presence
of 2- and 3-Phenylpropanal at 96 °C. In several cases,
aldehyde formation in hydroformylation has been shown to be
reversible.18 While extensive reversibility of aldehyde formation
would have led to 0% ee in the case of hydroformylation of
styrene by 1, the possibility existed that some aldehyde was
(18) (a) Lenges, C. P.; Brookhart, M. Angew. Chem., Int. Ed. 1999, 38, 3533.
(b) Brookhart, M.; Lenges, C. P.; White, P. S. J. Am. Chem. Soc. 1998,
120, 6965. (c) Kondo, T.; Akazome, M.; Tsuij, Y.; Watanabe, Y. J. Org.
Chem. 1990, 55, 1286.
(19) GC/MS showed only the natural abundance of deuterium in the recovered
2- and 3-phenylpropanal [2-phenylpropanal: m/e (intensity) [M + 2]+ 136
(0.13), [M + 1]+ 135 (1.64), [M]+ 134 (11.70); 3-phenylpropanal: [M +
2]+ 136 (0.63), [M + 1]+ 135 (6.10), [M]+ 134 (44.78)].
9
5590 J. AM. CHEM. SOC. VOL. 126, NO. 17, 2004

Hydroformylation of Styrene
A R T I C L E S
Figure 1. Leveling effect of H2 pressure on the n:i and % ee (S)-2-phenylpropanal in the hydroformylation of styrene at 50 °C and 400 psi CO.
Scheme 8
Discussion
We set out to understand the unusual observation that the
enantioselectivity in the hydroformylation of styrene with 1
reverses from 60% ee 2-(S) at 40 °C to 10% ee 2-(R) at 100 °C
(Scheme 2). From the beginning, we focused our attention on
the stage at which enantioselectivity is set at the two different
temperatures.
At 40 °C and equal pressures of syn gas (600 psi CO and
600 psi D2), deuterioformylation studies showed that the major
products had deuterium mainly â to the aldehyde carbonyl. This
establishes that the 2-(S) selectivity is set by largely irreversible
formation of alkyl platinum intermediates that are converted to
aldehydes. The small amount of deuterium found in recovered
styrene resulted from competing â-hydride elimination from the
alkyl platinum intermediates. It is estimated that the primary
alkyl intermediate goes on to aldehyde 4.25 times faster than it
eliminates styrene and the secondary alkyl intermediate goes
on to aldehyde 1.6 times faster than it eliminates styrene
(Scheme 4, blue, taking account of labeling statistics). Finding
deuterium in styrene but not in the R-position of aldehydes
suggests that intermediate platinum hydride alkene complexes
dissociate styrene much faster than they re-form an isomeric
platinum alkyl.
less than the 30% we associate with initial alkyl formation. As
CO pressure was increased from 200 to 1000 psi, the amounts
of 2-(S) and 3 increased slightly while the amount of 2-(R)
decreased significantly. We suggest that CO shifts the equilib-
rium of the n-alkyl (A) toward n-acyl (D) more than it shifts
that of the R-alkyl (B-(R)) to the R-acyl (C-(R)). Therefore, at
higher CO pressures, more of the n-acyl (D) is hydrogenolyzed
to aldehyde while more of the R-alkyl (B-(R)) reverts to the
pool of styrene, thus increasing the amount of 3 at the expense
of 2-(R). This CO dependence emphasizes the importance of
the equilibrium between platinum alkyls and platinum acyls.
The rates of â-hydride elimination, platinum acyl formation,
and platinum acyl hydrogenolysis are delicately balanced at 50
°C. CO inhibits â-hydride elimination from platinum alkyl, and
H2 takes platinum acyls on to aldehydes. The greatest amount
of 2-(S) is formed at lower temperature where â-hydride
elimination is disfavored, at high CO pressure where conversion
of the S-alkyl (B-(S)) to S-acyl (C-(S)) intermediate is acceler-
ated, and at high H2 pressure where the S-acyl (C-(S))
In H2 pressure dependence studies at 50 °C, the fraction of
2-(S) increased as the H2 pressure increased and plateaued at
about 32% 2-(S), 8% 2-(R), and 60% 3 (Scheme 8). These
percentages mirror the initial percentages of metal alkyls formed.
At high H2 pressures, acyl formation is less reversible because
as the acyl forms, it gets trapped immediately to form aldehyde.
This would account for the relatively low n:i ratio. At lower
H2 pressures, acyl hydrogenolysis is slower, as indicated by the
TOF, and is competitive with reversible acyl formation. Slow
hydrogenolysis therefore allows time for isomerization of the
platinum acyl by reversion all the way back to coordinated or
free styrene.
Another level of enantioselective control was discovered in
hydroformylation studies at 50 °C under 400 psi H2 and variable
CO pressure. Under these conditions, there is some reversibility
in the formation of the S-alkyl platinum intermediate B-(S)
because the amount of 2-(S) formed (23%) was significantly
9
J. AM. CHEM. SOC. VOL. 126, NO. 17, 2004 5591

A R T I C L E S
Casey et al.
Scheme 9. Effect of CO Pressure on the Rates of Hydrogenolysis
Scheme 10. Higher CO Pressure Increases the Ratio of
Hydroformylation to Hydrogenation
intermediate is hydrogenolyzed to 2-(S). It is also possible that
the equilibrium between SnCl3 and CO complexes is altered at
high CO pressures, and, as a result, the rate of hydrogenolysis
may also be affected (Scheme 9).
At 98 °C, deuterioformylation showed extensive deuterium
at the R- as well as â-positions of the aldehydes and extensive
incorporation of deuterium into styrene. This establishes that
formation of the alkyl platinum intermediates is reversible and
that enantioselectivity is set at a later stage in hydroformylation.
The primary alkyl was estimated to â-hydride eliminate 3.6
times faster than conversion to n-aldehyde, while the secondary
alkyl was estimated to eliminate 11.7 times faster than conver-
sion to iso-aldehyde.
Because the n:i and % ee 2-(R) decreased as the H2 pressure
increased at 100 °C, this indicates that enantioselectivity is not
fully set until hydrogenolysis of intermediate acyl complexes.
Upon going from 50 °C under 400 psi CO and 1000 psi H2 to
100 °C under 400 psi CO and 200 psi H2, the relative amount
of 2-(S) dropped from 32% to 9%, while the amounts of 2-(R)
increased from 8% to 13% and 3 increased from 59% to 79%.
This suggests that there is partial equilibration of acyl platinum
complexes via reversion all the way back to free styrene at high
temperature and that the relative rate of hydrogenolysis of the
S-acyl (C-(S)) is slower than hydrogenolysis of either the R-acyl
(C-(R)) or the n-acyl (D) at high temperature by a factor of
about 6.20
Because CO pressure did not affect the rate or selectivity of
hydroformylation at 100 °C, the resting state of the catalyst and
the transition state for hydrogenolysis must have the same
number of CO’s. Because higher CO pressures slowed hydro-
genation to ethylbenzene, the transition state for hydroformy-
lation has one more CO than the hydrogenation transition state
(Scheme 10).
slow step in both processes involves H2. The % hydrogenation
to ethylbenzene did not depend on H2 pressure because both
aldehyde formation and hydrogenation depend of H2 pressure
equally.
Why does the selectivity-determining step change as a
function of temperature? It all has to do with the greater
temperature dependence of a first order reaction (∆Hq ) larger,
∆Sq ≈ 0) as compared to a competing second order reaction
(∆Hq ) smaller, ∆Sq , 0). Alkyl formation and â-hydride
elimination are first order reactions, whereas acyl formation and
acyl hydrogenolysis are second order reactions involving CO
and H2, respectively. At 40 °C, the first order elimination of
the platinum alkyl back to styrene is slower than its second
order reaction with CO to give an acyl complex that is converted
on to aldehyde. At 40 °C, selectivity is largely set by the first
order formation of platinum alkyls. At 100 °C, the first order
elimination of the platinum alkyl back to styrene is accelerated
more than the second order acyl formation and the second order
hydrogenolysis of the acyl complex. At 100 °C, the selectivity
is not determined until the second order hydrogenolysis of the
acyl intermediates.
Acknowledgment. Financial support from the Department
of Energy, Office of Basic Energy Sciences, is gratefully
acknowledged. Grants from the NSF (Grant No. CHE-9629688)
and the NIH (Grant No. I S10 RR04981-01) for the purchase
of NMR spectrometers and from the NSF (Grant No. CHE-
9310428) for the purchase of X-ray instruments are also
acknowledged. Douglas R. Powell and Michael A. Kozee are
also acknowledged for solving the X-ray crystal structure of
the Pt catalyst.
The rates of formation (TOF) of ethylbenzene and of aldehyde
both increased at higher H2 pressures. This indicates that the
Supporting Information Available: Preparation and charac-
terization of substrates, kinetics experimental details, tables
giving X-ray crystallographic data for complex 1, and graphs
(PDF and CIF). This material is available free of charge via
the Internet at http://pubs.acs.org.
(20) This value was obtained by taking the product ratios at 50 °C and high H2
pressure as the initial ratios for the formation of the corresponding acyl
intermediates and comparing them to the product ratios at 100 °C and low
H2 pressure. The formula for calculating the ratio of R-acyl cleavage to
S-acyl cleavage is: (8y × 9) ) (13 × 32) where y ) 5.8, the rate at which
the R-acyl is cleaved as compared to cleavage of the S-acyl.
JA0318479
9
5592 J. AM. CHEM. SOC. VOL. 126, NO. 17, 2004