Mechanistic insights into hydroacylation with non-chelating aldehydes

Article abstract of DOI:10.1039/c4sc02026j

The combination of a small-bite-angle diphosphine bis(dicyclohexylphosphino)methane (dcpm) and [Rh(cod)OMe]₂ catalyses the hydroacylation of 2-vinylphenols with a wide range of non-chelating aldehydes. Here we present a detailed experimental st

Full text of DOI:10.1039/c4sc02026j

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Mechanistic insights into hydroacylation with
non-chelating aldehydes†
Cite this: DOI: 10.1039/c4sc02026j
a
a
Stephen K. Murphy,ab Achim Bruch and Vy M. Dong
*
The combination of a small-bite-angle diphosphine bis(dicyclohexylphosphino)methane (dcpm) and
[Rh(cod)OMe]2 catalyses the hydroacylation of 2-vinylphenols with a wide range of non-chelating
aldehydes. Here we present a detailed experimental study that elucidates the factors contributing to the
broad aldehyde scope and high reactivity. A variety of catalytically relevant intermediates were isolated
and a [Rh(dcpm)(vinylphenolate)] complex was identified as the major catalytically relevant species.
A variety of off-cycle intermediates were also identified that can re-enter the catalytic cycle by
substrate- or 1,5-cyclooctadiene-mediated pathways. Saturation kinetics with respect to the
2-vinylphenol were observed, and this may contribute to the high selectivity for hydroacylation over
aldehyde decarbonylation. A series of deuterium labelling experiments and Hammett studies support the
oxidative addition of Rh to the aldehyde C–H bond as an irreversible and turnover-limiting step. The
small bite angle of dcpm is crucial for lowering the barrier of this step and providing excellent reactivity
with a variety of aldehydes.
Received 9th July 2014
Accepted 27th August 2014
DOI: 10.1039/c4sc02026j
www.rsc.org/chemicalscience
of aldehydes with a,b-unsaturated carbonyl compounds,
1,3-dienes, cyclopropenes, and some styrenes. Developing
Introduction
methods that provide the alternative branched products
without relying on chelating aldehydes would enable access to
unique chemical space by hydroacylation.
Central challenges in Rh-catalysed olen hydroacylation are to
promote aldehyde C–H activation while preventing decarbony-
lation, and to control the regioselectivity of C–C bond formation
(Fig. 1).1 Most intermolecular hydroacylations are inherently
linear-selective and rely on chelating aldehydes such as salicy-
laldehydes,2 2-aminobenzaldehydes,3 b-sulphur aldehydes,4 or
2-pyridylaldimines5 to promote C–H activation and suppress
decarbonylation. Brookhart, Tanaka, and Jun have made
breakthroughs in the eld by developing linear-selective
protocols with non-chelating aldehydes.6 Alternatively, Co
catalysts,7 Ru hydrides8 and N-heterocyclic carbenes9 have
emerged as promising catalysts for the linear-selective coupling
We recently reported a strategy for branched-selective
hydroacylation with an aldehyde scope that is among the most
broad reported to date (Fig. 2).10 Alkyl, alkenyl, and aryl alde-
hydes were coupled with 2-vinylphenols in generally >20 : 1
branched-to-linear (b : l) selectivity and excellent yields. We
hypothesized that the phenolic group on the olen promotes
the branched regioselectivity in analogy to our double-chelating
hydroacylations with salicylaldehydes.2c–e
A [Rh(cod)OMe]2
catalyst in combination with a small-bite-angle diphosphine,
bis(dicyclohexylphosphino)methane (dcpm), was crucial for
reactivity. This method enabled short syntheses of four
Fig. 1 Intermolecular olefin hydroacylation.
aDepartment of Chemistry, University of California, Irvine, California, 92697-2025,
USA. E-mail: dongv@uci.edu
bDepartment of Chemistry, University of Toronto, 80 St. George Street, Toronto,
Ontario M5S 3H6, Canada
† Electronic supplementary information (ESI) available: Materials and methods,
reaction procedures, characterization data. CCDC 1012849. For ESI and
crystallographic data in CIF or other electronic format see DOI:
10.1039/c4sc02026j
Fig.
2 Intermolecular 2-vinylphenol hydroacylation and cyclo-
condensation to access benzofuran natural products.
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neolignan natural products using hydroacylation in combina- appeared between 2 and 4 ppm—within the range of coordi-
tion with an acid-catalysed cyclocondensation. Herein we report nated olens. The 13C NMR showed coupling between the
a mechanistic study that sheds light on the catalyst resting vinylic carbon atoms and the Rh center (JRh–C ¼ 11 and 15 Hz).
states of this transformation, the rate-limiting step, and the Based on this data and the ESIꢀ MS, we assigned this
properties of the substrates and ligands that enable reactivity complex as an anionic 2 : 1 vinylphenolate-to-Rh complex 9. To
with non-chelating aldehydes.
support our assignment of anion 9, the [(18-crown-6)K]-
[Rh(nitrovinylphenolate)2] salt 10 was synthesized by treating
two equivalents of 4-nitro-2-vinylphenol with [Rh(cod)OMe]2,
t-BuOK and 18-crown-6 (Fig. 3, bottom). The solid state struc-
ture of salt 10 (Fig. 3, right) contains two vinylphenolate anions
bound to a Rh atom in a cis orientation, where the phenolate
oxygen atoms bind to the potassium centre. Only small differ-
ences in chemical shi were noted between 9 and 10, which are
likely due to potassium coordination in 10. Additionally, small
shoulder peaks were noted in the 1H NMR spectrum of 9, which
are likely a result of geometrical isomers.
Given that the double salt of 4 and 9 accounts for nearly 60%
of the Rh during catalysis, the reactivity of these species strongly
correlates with the activity of the overall catalyst system. We
thus decided to examine the reactivity of each ion indepen-
dently by studying complexes 8 ([Rh(dcpm)2]BF4) and 10 [(18-
Results and discussion
A. Assignment of catalyst resting states
To identify potential reaction intermediates, we monitored the
31P NMR of
a catalytic hydroacylation involving hydro-
cinnamaldehyde (1) and 4-nitro-2-vinylphenol (2) (Table 1). At
12% conversion, four different phosphorus-containing
complexes (4, 5, 6 and 7) were detected in an approximately
3 : 3 : 1 : 1 ratio, respectively, based on integration of the 31P
NMR signals. Over the course of catalysis, complexes 5 and 6
decreased in concentration while only complexes 4 and 7
remained at the end of the reaction.
The major complex 4 was prepared by reacting [Rh(cod)
OMe]2 with dcpm and 4-nitro-2-vinylphenol in a 1 : 2 : 2 molar
ratio in THF (Fig. 3, top). A cationic [Rh(dcpm)2]+ fragment was
identied by ESI+ MS and by comparison of the NMR data with
that of [Rh(dcpm)2]BF4 (8). The synthesis of 4 was accompanied
by quantitative formation of 1,5-cyclooctadiene, MeOH and
another Rh complex 9, containing a coordinated vinylphenolate
crown-6)K][Rh(nitrovinylphenolate)2]
(Table
2).
While
[Rh(diphosphine)2]+ complexes catalyse the cyclization of 4-
pentenals at elevated temperatures,11 complex 8 did not catalyse
vinylphenol hydroacylation even in the presence of base
(t-BuOK, entries 2 and 3). Salt 10 also did not catalyse hydro-
acylation (entry 4), but it could be activated by dcpm to give an
initial turnover frequency (TOFinit) four times lower than the
1
anion as judged by H NMR analysis. The aromatic protons of
the vinylphenolate were shied upeld and the vinylic peaks
optimized reaction (entries 1 and 5, 15 hꢀ1 versus 4 hꢀ1
,
respectively). Although this rate is low, the observation of
catalysis supports the intermediacy of phosphine-ligated
species and suggests that 4 and 9 are not directly on the catalytic
cycle. The combination of 8, 10, and 1,5-cyclooctadiene resulted
in slow catalysis (entries 6 and 7, approx. 50% conv. aer 24
hours). Apparently, the 1,5-cyclooctadiene converts the double
salt back to a catalytically active species, although this effect is
likely smaller than the inhibitory effect of 1,5-cyclooctadiene
that occurs due to binding of the active catalyst (vide infra).
Complex 7 is the next most abundant Rh complex during
catalysis, and was identied as a cationic [Rh(dcpm)(cod)]+
fragment by comparison of the 31P NMR spectrum to that of
[Rh(dcpm)(cod)]BF4 (11). This latter complex is a kinetically
competent catalyst in the presence of t-BuOK and provides a
similar initial turnover frequency to the optimized conditions
(18 hꢀ1 versus 15 hꢀ1, respectively).12 When a suspension of 4-
nitro-2-vinylphenol and t-BuOK was vigorously stirred with
complex 11, a nearly quantitative exchange reaction occurred to
generate substrate-bound 5 (Fig. 4). In the presence of excess
aldehyde, the olen ligand of complex 5 exchanges with the
aldehyde to generate intermediate 6, which is observed during
catalysis. Complex 6 is only observed transiently and undergoes
hydroacylation and a substitution reaction at room temperature
to form cation 7 and anion 3ꢀ, which aggregates with excess
phenols as judged by ESIꢀ MS.
Table 1 31P NMR spectrum of a catalytic reaction at 12% conversion
Complex
d (ppm)
JRh–P (Hz)
JP–P (Hz)
4
5
6
7
ꢀ17.0
111
—
92
69
—
Our investigation of catalyst resting states reveals that 5 and
6 are directly on the catalytic cycle, while a variety of off-cycle
intermediates can re-enter the cycle via pathways mediated by
0.7, ꢀ26.9
1.7, ꢀ9.9
ꢀ26.4
125, 148
126, 117
126
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Fig. 3 Synthesis of [Rh(vinylphenolate)2]ꢀ complexes.
Table 2 Hydroacylation with various Rh complexes
2-vinylphenolate moiety. Formation of the acyl-Rh-hydride
would likely be followed by rapid coordination of the olen to
generate a coordinatively saturated intermediate that is stable
towards decarbonylation,13 thus providing the desired
chemoselectivity.
B. Kinetic analysis using in situ NMR monitoring of reaction
progress
Entry
Catalyst
Additive
Yieldb (%)
Time (h)
To identify kinetic parameters, we studied the hydroacylation of
4-nitro-2-vinylphenol under catalytic conditions with various
amounts of hydrocinnamaldehyde (Fig. 5). The coupling reac-
tion with 1.5 equivalents of hydrocinnamaldehyde follows a
curved reaction prole with an initial turnover frequency of
15 hꢀ1 and no induction period. Decreasing the aldehyde
concentration by half decreases the initial turnover frequency
by half (8 hꢀ1), a result that suggests a rst order dependence of
the rate on aldehyde concentration. Using a large excess of
aldehyde (8 equiv) yields a reaction prole that is linear up to
80% conversion with an initial turnover frequency of only
23 hꢀ1. Analysing the 31P spectrum under these highly
a
1
2
3
4
5
6
7
[Rh(cod)OMe]2
8
8
10
10
8/10
8/10
dcpm
—
t-BuOK
—
dcpm
—
cod
>95
n.r.
n.r.
n.r.
80
2
—
—
—
12
—
24
n.r.
50
a
4 mol% catalyst. b n.r. ¼ no reaction.
Fig. 4 Formation of the olefin-bound complex and its behaviour in
the presence of excess aldehyde (R ¼ CH2Bn).
1,5-cyclooctadiene or 2-vinylphenol. The strong coordination of
the 2-vinylphenol compared to the aldehyde is likely a key to
promoting hydroacylation over competitive decarbonylation. Of
the observed Rh complexes, oxidative addition would only be
Fig.
5 Kinetic data for hydroacylation with various amounts of
possible from 6, which already contains the O-coordinated hydrocinnamaldehyde.
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Table
3
Deuterium labelling studies (olefin
¼
4-nitro-2-
vinylphenol)a,b,c
Fig. 6 Concentration-dependent chemoselectivity for hydroacylation
over aldol dehydration.
Entry
Ligandd
R
Time (h)
Yield (%)
b : l
1
2
3
4
5
dcpm
dcpm
dcpe
dcpp
dcpb
2-nap
24
2
12
12
12
78
90
45
41
35
12 : 1
concentrated conditions reveals that the equilibrium between 5
and 6 is completely shied toward 6. The formation of 6, which
contains both a coordinated aldehyde and phenolate, leads to
saturation kinetics with respect to both substrates. Under
typical catalytic conditions, however, this kinetic data and the
assignment of catalyst resting states supports a rst order
dependence of the rate on aldehyde concentration and a zeroth
order dependence on 2-vinylphenol concentration. These
results corroborate the concentration-dependent selectivity for
hydroacylation over competitive aldol dehydration (Fig. 6).
The substrate 6-methyl-2-vinylphenol (12) undergoes slow
hydroacylation due to its steric bulk, which allows the aldehyde
to be consumed by dimerization. However, greater chemo-
selectivity for hydroacylation over aldol dehydration was
observed upon vefold dilution. Diluting the reaction slows
down aldol dehydration (second order in aldehyde) more
dramatically than vinylphenol hydroacylation (rst order in
aldehyde, zeroth order in vinylphenol).
CH2Bn
CH2Bn
CH2Bn
CH2Bn
>20 : 1
>20 : 1
>20 : 1
>20 : 1
a
b : l ratios were determined by NMR analysis of the crude
b
reaction mixtures. Entry 1: 1,4-dioxane, 100 ꢂC. Entries 2–5: THF,
60 ꢂC. Deuterium content measured by 1H and 2D NMR, and
c
d
ESI MS. dcpe ¼ 1,2-bis(dicyclohexylphosphino)ethane; dcpp ¼ 1,3-
bis(dicyclohexylphosphino)propane; dcpb
phosphino)butane.
¼
1,4-bis(dicyclohexyl-
To further probe the turnover-limiting step, we measured
kinetic isotope effects (KIE) via intermolecular competition
experiments of deuterated aldehydes with their protio
analogues.16 With 4-nitro-2-vinylphenol as the coupling partner,
a KIE of 2.5 ꢁ 0.2 was observed for the reaction with hydro-
cinnamaldehyde and 2.4 ꢁ 0.2 for the reaction with 2-naph-
thaldehyde. The similar magnitudes of the KIE values indicate
that these reactions proceed by similar mechanisms. We
recently reported a KIE of 2.6 for an intermolecular ketone
hydroacylation with non-chelating aldehydes, in which oxida-
tive addition of Rh to the aldehyde C–H bond was rate
limiting.17 Madsen reported a similar value of 2.85 for the
oxidative addition of aldehydes to Rh(dppp)+.18 Lower KIE
values of 1.4–1.7 are associated with hydroacylation reactions
that involve rate-limiting migratory insertion or reductive
elimination.19,4e The large primary KIEs observed in the present
case suggest that irreversible oxidative addition is likely the
turnover-limiting step.
C. Deuterium labelling studies
We probed the turnover-limiting step of the reaction by tracking
the deuterium label for hydroacylation with deuterated
2-naphthaldehyde (Table 3, entry 1). This substrate coupled
with 4-nitro-2-vinylphenol in 78% yield and 12 : 1 b : l selec-
tivity. 1H and 2D NMR analysis revealed that deuterium was
incorporated into only the b-positions of the resulting ketones.
Analysis of the products by mass spectrometry revealed that
they were exclusively monodeuterated. Analogous results were
obtained for the reaction of deuterated hydrocinnamaldehyde
with 4-nitro-2-vinylphenol (Table 3, entry 2). The lack of
deuterium scrambling and multiply-deuterated products rules
out reductive elimination as the turnover-limiting step and
suggests that at least one of the earlier steps in the catalytic
cycle is irreversible.
D. Hammett studies
We conducted a Hammett study by reacting different para-
substituted
benzaldehydes
with
4-nitro-2-vinylphenol
This observation contrasts almost all other olen hydro-
acylation studies where extensive deuterium-scrambling is
observed as a result of rate-limiting reductive elimination.14,15
When larger-bite-angle diphosphines were used in the test for
deuterium scrambling (Table 3, entries 3–5), the reaction rates
were signicantly reduced, deuterium scrambling still did not
occur, and only monodeuterated products were identied. These
results suggest that reductive elimination is not rate-deter-
mining for this substrate combination, regardless of ligand bite
angle. Accordingly, the fact that smaller-bite-angle diphosphines
(Fig. 7).20,21 Aldehydes with electron-withdrawing substituents
reacted faster, while those with electron-donating groups reac-
ted slower. A positive r value of 0.79 was measured, which
indicates a build-up of negative charge in the transition state of
the turnover-limiting step. This description is consistent with
the transition state for oxidative addition of Rh to the aldehyde
C–H bond.22
E. Rationale for the ligand effects
provide faster rates can be attributed to their abilities to promote Having established the catalyst resting states and the turn-
earlier steps in the catalytic cycle (vide infra).
over-limiting step, we conclude that the rate of 2-vinylphenol
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increased steric bulk. Our results contrast ndings on the
+
addition of H2 to Rh(diphosphine)2 complexes, and the
hydroacylation of alkenes with b-sulfur-substituted alde-
hydes. In the rst case, wider bite angles favoured oxidative
addition as a result of an electronic bite-angle effect;24 and in
the latter case, small-bite-angle diphosphines promoted a
rate-limiting reductive elimination.4e
F. Proposed mechanism
On the basis of our experimental evidence and literature
precedence, we propose the mechanism shown in Fig. 8. The
catalyst precursor [Rh(cod)OMe]2 reacts with dcpm and
vinylphenol 2 to form either the catalytically inactive double
salt of 4 and 9 or the major catalyst resting state 5. Exchange
of the olen ligand for aldehyde 1 leads to intermediate 6.
Both complexes 5 and 6 are catalyst resting states and they
decrease in concentration as the reaction progresses. Sup-
ported by kinetic isotope effects and a Hammett study, we
propose that oxidative addition is turnover-limiting. The
resulting acyl-RhIII-hydride 14 does not reductively decar-
bonylate to any measurable extent, but instead undergoes
migratory insertion to yield intermediate 15.25 Reductive
elimination and displacement of the product 3 with substrate
2 completes the catalytic cycle. Alternatively, 1,5-cyclo-
octadiene can displace either the vinylphenol (2) or product
(3) to form the off-cycle intermediate 7, which increases in
concentration during catalysis. The counterion of 7 is a
dissociated phenolate anion that can hydrogen bond with
excess substrate or product.
Fig. 7 Hammett study for para-substituted benzaldehydes.
hydroacylation is dictated predominantly by the rate of
oxidative addition. Thus, the ligand dcpm likely accelerates
this key step relative to its wide-bite-angle counterparts. To
better understand the steric component of this effect,23 we
examined the reactivity of the ligand (tBu)2PCH2P(tBu)(Me),
which has a larger steric prole than dcpm but similar elec-
tronic properties and bite angle. This ligand did not provide
an active catalyst. We thus propose that the small size of
dcpm reduces steric repulsion in the transition state for
oxidative addition. A pronounced electronic effect is also
apparent, based on the comparison of dcpm with dppm
(bis(diphenylphosphino)methane):
faster
rates
were
observed with the more basic disphosphine dcpm, despite its
Fig. 8 Proposed mechanism for vinylphenol hydroacylation (4-nitro group omitted from the vinylphenol, R ¼ CH2Bn).
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Soc., 2010, 132, 16354; (k) M. von Delius, C. M. Le and
V. M. Dong, J. Am. Chem. Soc., 2012, 134, 15022.
Conclusions
3 M. Castaing, S. L. Wason, B. Estepa, J. F. Hooper and
M. C. Willis, Angew. Chem., Int. Ed., 2013, 52, 13280.
4 For hydroacylation with b-sulfur substituted aldehydes, see:
(a) M. C. Willis, S. J. McNally and P. J. Beswick, Angew. Chem.,
Int. Ed., 2004, 43, 340; (b) G. L. Moxham, H. E. Randell-Sly,
S. K. Brayshaw, R. L. Woodward, A. S. Weller and
M. C. Willis, Angew. Chem., Int. Ed., 2006, 45, 7618; (c)
G. L. Moxham, H. E. Randell-Sly, S. K. Brayshaw,
A. S. Weller and M. C. Willis, Chem. – Eur. J., 2008, 14,
8383; (d) J. D. Osborne and M. C. Willis, Chem. Commun.,
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M. C. Willis, J. Am. Chem. Soc., 2012, 134, 4885; (f)
I. Pernik, J. F. Hooper, A. B. Chaplin, A. S. Weller and
M. C. Willis, ACS Catal., 2012, 2, 2779.
5 For (2-pyridyl)aldimines, see: (a) J. W. Suggs, J. Am. Chem.
Soc., 1979, 101, 489; (b) C.-H. Jun, J.-B. Kang and J.-Y. Kim,
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6 (a) Y. J. Park, J.-W. Park and C.-H. Jun, Acc. Chem. Res., 2008,
41, 222; (b) K. Tanaka, Y. Shibata, T. Suda, Y. Hagiwara and
M. Hirano, Org. Lett., 2007, 9, 1215; (c) Y. Shibata and
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We have disclosed a thorough mechanistic study on the
branched-selective hydroacylation of 2-vinylphenols with a wide
range of aryl, alkenyl, and alkyl aldehydes. Analysis of the
catalyst resting states revealed that most of the catalyst is
sequestered as an inactive double salt of Rh, while the active
catalyst consists of a Rh(dcpm)(vinylphenolate) fragment. Non-
directed oxidative addition of Rh to the aldehyde C–H bond
occurs even at room temperature, followed by rapid hydro-
acylation. This strong binding of the vinylphenolate is likely a
key to promoting hydroacylation over competitive aldehyde
decarbonylation and aldol dehydration. KIE measurements and
a Hammett study support oxidative addition as the turnover-
limiting step. The high reactivity of neutral [Rh(X)(dcpm)]
fragments likely arises from the electron-rich character of the
complex, and small bite angle of the diphosphine, which
promotes oxidative addition. In contrast, previous studies that
use chelating aldehydes involve a fast and reversible C–H bond
activation. This difference in mechanism highlights the chal-
lenge of non-directed aldehyde activation. Given the mild
conditions of this transformation, [Rh(X)(dcpm)] fragments
hold promise for future hydroacylations with non-chelating
aldehydes.
Acknowledgements
We thank the National Institutes of Health (GM105938) for
funding. S.K.M. is grateful for a Canada Graduate Scholarship
(CGS), and A.B. is grateful for a fellowship within the Postdoc-
Programme of the German Academic Exchange Service (DAAD).
We thank Dr Joseph W. Ziller and Jordan Corbey for X-ray
crystallographic analysis.
7 Q. A. Chen, D. K. Kim and V. M. Dong, J. Am. Chem. Soc.,
2014, 136, 3772.
8 For branched-selective hydroacylation using complementary
Ru-hydride catalysis, see: (a) T. Fukuyama, T. Doi,
S. Minamino, S. Omura and I. Ryu, Angew. Chem., Int. Ed.,
2007, 46, 5559; (b) S. Omura, T. Fukuyama, J. Horiguchi,
Y. Murakami and I. Ryu, J. Am. Chem. Soc., 2008, 130,
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Am. Chem. Soc., 2008, 130, 14120; (d) For a review of
hydroacylation methods that proceed by a mechanism
other than aldehyde C–H bond activation, see: J. C. Leung
and M. J. Krische, Chem. Sci., 2012, 3, 2202.
9 For styrenes, see: (a) M. Schedler, D.-S. Wang and F. Glorius,
Angew. Chem., Int. Ed., 2013, 52, 2585; (b) For cyclopropenes,
see: X. Bugaut, F. Liu and F. Glorius, J. Am. Chem. Soc., 2011,
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Stetter reaction with a,b-unsaturated carbonyl compounds,
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D. H. T. Phan, K. G. M. Kou and V. M. Dong, J. Am. Chem.
Chem. Sci.
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10 S. K. Murphy, A. Bruch and V. M. Dong, Angew. Chem., Int. 17 K. G. M. Kou, D. N. Le and V. M. Dong, J. Am. Chem. Soc.,
Ed., 2014, 53, 2455. 2014, 136, 9471.
11 (a) B. R. James and C. G. Young, J. Chem. Soc., Chem. 18 P. Fristrup, M. Kreis, A. Palmelund, P.-O. Norrby and
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12 We expected catalyst 11 to exhibit a faster rate than the
R. Madsen, J. Am. Chem. Soc., 2008, 130, 5206.
19 Z. Shen, P. K. Dornan, H. A. Khan, T. K. Woo and V. M. Dong,
J. Am. Chem. Soc., 2009, 131, 1077.
optimized reaction because none of the Rh would be 20 For use of a Hammett plot to study the mechanism of
sequestered as the double salt of 4 and 9. The fact that 11
Rh(dppp)+ catalysed aldehyde decarbonylation, see ref. 18.
provides only a slightly higher initial TOF than the 21 In line with our observation of saturation kinetics with
optimized reaction is likely a result of the low solubility of
the t-BuOK–vinylphenol mixture and the lack of stirring
during NMR analysis.
respect to the 2-vinylphenol, modifying the 2-vinylphenols
at the 3 or 4 position also changes the reaction rate even
though the substrate does not appear in the rate equation.
More electron rich 2-vinylphenols appear to react slower
than electron decient substrates, but electron rich
substrates also lead to unidentied side-products.
13 (a) D. Milstein, Organometallics, 1982, 1, 1549; (b)
D. Milstein, J. Chem. Soc., Chem. Commun., 1982, 1357.
14 For examples of hydroacylation where deuterium
scrambling is observed as
a result of rate-limiting 22 For the effect of electronics on oxidative addition, see: (a)
reductive elimination, see: (a) R. E. Campbell,
C. F. Lochow, K. P. Vora and R. G. Miller, J. Am. Chem.
Soc., 1980, 102, 5824; (b) R. E. Campbell and R. G. Miller, J.
L. Xue and Z. Lin, Chem. Soc. Rev., 2010, 39, 1692; (b)
K. Wang, T. J. Emge, A. S. Goldman, C. Li and S. P. Nolan,
Organometallics, 1995, 14, 4929; (c) Ref. 6d.
Organomet. Chem., 1980, 186, C27; (c) D. P. Fairlie and 23 (a) For case studies on the steric and electronic components
B. Bosnich, Organometallics, 1988, 7, 946; (d) I. F. D. Hyatt,
H. K. Anderson, A. T. Morehead Jr and A. L. Sargent,
Organometallics, 2008, 27, 135; (e) Ref. 6d; (f) Ref. 2d; (g)
Ref. 2b.
of the bite angles effect of various catalytic reactions, see:
Z. Freixa and P. W. N. M. van Leeuwen, Dalton Trans.,
2003, 1890; (b) For
a
comparison of dppm and
(tBu)2PCH2(tBu)2 in CO/ethylene oligomerization, see:
E. Drent, J. A. M. Broekhoven and M. J. Doyle, J.
Organomet. Chem., 1991, 417, 235; (c) C. Bianchini,
H. M. Lee, A. Meli, W. Oberhauser, M. Peruzzini and
F. Vizza, Organometallics, 2002, 21, 16.
15 To our knowledge, there are only two examples of olen
hydroacylation where reductive elimination has been ruled
out as the rate-limiting step, see: (a) M. C. Coulter,
P. K. Dornan and V. M. Dong, J. Am. Chem. Soc., 2009, 131,
6932; (b) Ref. 2k.
24 D. L. DuBois, D. M. Blake, A. Miedaner, C. J. Curtis,
M. R. DuBois, J. A. Franz and J. C. Linehan,
Organometallics, 2006, 25, 4414.
16 An intermolecular KIE experiment is appropriate for this
system given that C–H bond cleavage is the rst step in the
catalytic cycle and our observed catalyst resting states 25 Branched-selective migratory insertion is generally fast and
([Rh(dcpm)(vinylphenolate)])
[Rh(dcpm)(vinylphenolate)(aldehyde)]
aldehyde activation. For a discussion on KIEs in metal
catalysis, see: (a) E. M. Simmons and J. F. Hartwig, Angew.
and
precede
reversible for olen hydroacylation, whereas linear-
selective insertion has a higher barrier, see: (a) Ref. 16b;
(b) Ref. 2d; (c) Ref. 15g; (d) for a related example of the
hydroformylation reaction, see: C. P. Casey and
L. M. Petrovich, J. Am. Chem. Soc., 1995, 117, 6007.
directly
´
Chem., Int. Ed., 2012, 51, 3066; (b) M. Gomez-Gallego and
M. A. Sierra, Chem. Rev., 2011, 111, 4857.
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Chem. Sci.