Intermolecular hydroacylation: High activity rhodium catalysts containing small-bite-angle diphosphine ligands

Article abstract of DOI:10.1021/ja211649a

Readily prepared and bench-stable rhodium complexes containing methylene bridged diphosphine ligands, viz. [Rh(C₆H₅F)(R ₂PCH₂PR'₂)][BAr^F₄] (R, R' = ^tBu or Cy; Ar^F = C₆H₃-3,5- (CF₃)₂), are shown to be practical and very efficient precatalysts for the intermolecular hydroacylation of a wide variety of unactivated alkenes and alkynes with β-S-substituted aldehydes. Intermediate acyl hydride complexes [Rh(^tBu₂PCH ₂P^tBu₂)H{κ²(S,C)-SMe(C ₆H₄CO)}(L)]⁺ (L = acetone, MeCN, [NCCH ₂BF₃]^-) and the decarbonylation product [Rh(^tBu₂PCH₂P^tBu₂)(CO) (SMePh)]⁺ have been characterized in solution and by X-ray crystallography from stoichiometric reactions employing 2-(methylthio) benzaldehdye. Analogous complexes with the phosphine 2-(diphenylphosphino) benzaldehyde are also reported. Studies indicate that through judicious choice of solvent and catalyst/substrate concentration, both decarbonylation and productive hydroacylation can be tuned to such an extent that very low catalyst loadings (0.1 mol %) and turnover frequencies of greater than 300 h^-1 can be achieved. The mechanism of catalysis has been further probed by KIE and deuterium labeling experiments. Combined with the stoichiometric studies, a mechanism is proposed in which both oxidative addition of the aldehyde to give an acyl hydride and insertion of the hydride into the alkene are reversible, with the latter occurring to give both linear and branched alkyl intermediates, although reductive elimination for the linear isomer is suggested to have a considerably lower barrier.

Full text of DOI:10.1021/ja211649a

Article
pubs.acs.org/JACS
Intermolecular Hydroacylation: High Activity Rhodium Catalysts
Containing Small-Bite-Angle Diphosphine Ligands
Adrian B. Chaplin,† Joel F. Hooper,‡ Andrew S. Weller,*,† and Michael C. Willis*,‡
†Department of Chemistry, Inorganic Chemistry Laboratories, University of Oxford, South Parks Road,
Oxford OX1 3QR, U.K.
‡Department of Chemistry, University of Oxford Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, U.K.
S
* Supporting Information
ABSTRACT: Readily prepared and bench-stable rhodium
complexes containing methylene bridged diphosphine ligands,
viz. [Rh(C6H5F)(R2PCH2PR′2)][BArF ] (R, R′ = tBu or Cy; ArF =
4
C6H3-3,5-(CF3)2), are shown to be practical and very efficient
precatalysts for the intermolecular hydroacylation of a wide
variety of unactivated alkenes and alkynes with β-S-substituted
aldehydes. Intermediate acyl hydride complexes [Rh(tBu2PCH2-
PtBu2)H{κ2(S,C)-SMe(C6H4CO)}(L)]+ (L = acetone, MeCN,
[NCCH2BF3]−) and the decarbonylation product [Rh-
(tBu2PCH2PtBu2)(CO)(SMePh)]+ have been characterized in solution and by X-ray crystallography from stoichiometric
reactions employing 2-(methylthio)benzaldehdye. Analogous complexes with the phosphine 2-(diphenylphosphino)-
benzaldehyde are also reported. Studies indicate that through judicious choice of solvent and catalyst/substrate concentration,
both decarbonylation and productive hydroacylation can be tuned to such an extent that very low catalyst loadings (0.1 mol %)
and turnover frequencies of greater than 300 h−1 can be achieved. The mechanism of catalysis has been further probed by KIE
and deuterium labeling experiments. Combined with the stoichiometric studies, a mechanism is proposed in which both oxidative
addition of the aldehyde to give an acyl hydride and insertion of the hydride into the alkene are reversible, with the latter
occurring to give both linear and branched alkyl intermediates, although reductive elimination for the linear isomer is suggested
to have a considerably lower barrier.
Scheme 1. Mechanism for Linear-Selective Alkene
Hydroacylation Using Rh-Diphosphine Catalysts
INTRODUCTION
■
The hydroacylation reaction is a potentially powerful trans-
formation in organic and materials synthesis, that allows for the
100% atom-efficient production of ketones from the combina-
tion of an alkene or alkyne with an aldehyde by sequential
C−H activation and C−C bond formation (eq 1).1−4 These
processes are at present best catalyzed by cationic rhodium−
diphosphine complexes, as first reported by Bosnich, e.g.
5,6
2+
[Rh(dppe)]2
.
These are complemented by [MCp(η2-
H2CCHSiMe3)2][BArF ] (M = Co, Rh; ArF = C6H3-3,5-
4
(CF3)2) catalysts developed by Brookhart.7,8 The accepted
mechanism for this reaction with a diphosphine catalyst
(Scheme 1)1,4−6,8−12 involves aldehyde oxidative addition to
give an acyl hydride intermediate (A) followed by alkene
coordination and hydride insertion (rather than acyl migration)
to give complex C, at which point linear/branched selectivity
can also arise.13,14 Reductive elimination of the ketone product
completes the cycle and is generally accepted to be turnover
limiting for alkene hydroacylation.6−8,10,11 Extension of this
methodology to carbonyl hydroacylation is also known.12,15−17
Recently, ruthenium hydrides have also been shown to promote
hydroacylation, although the mechanism is different from that
proposed for rhodium catalysts.18,19
The Achilles heel of this process is the irreversible reductive
decarbonylation from the acyl hydride (A to E via D), that
generates R−H (R = alkyl or aryl) and a considerably less active
metal−carbonyl. The carbonyl deinsertion step in this process
requires a vacant coordination site cis to the acyl.20 For intra-
molecular hydroacylation, for example using 4-pentenals,5,21,22
Received: December 14, 2011
Published: February 10, 2012
© 2012 American Chemical Society
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decarbonylation is attenuated by chelate-assisted olefin
coordination. For intermolecular hydroacylation, substrate-
derived chelation-assisted strategies have also been developed
to address decarbonylation,4,23−27 in which carbonyl dein-
sertion is disfavored due to ring strain. For example, we have
developed the use of β-S-substituted aldehydes to deliver
productive hydroacylation catalysis using dppe-derived Rh(I)
catalysts.28−34 A complementary, catalyst-centered, approach is
the use of the hemilabile diphosphine ligand, DPEphos, that
reversibly binds to the cis-vacant site while also allowing access
by the olefin.10,35 An alternative methodology involves the use
of Cp*−Rh(I) derived catalysts. In these systems reversible
carbonyl deinsertion occurs (and is in fact the resting state in
catalysis), but reductive elimination is unfavorable in the co-
ordinatively saturated alkyl-hydrido-carbonyl intermediate.7,8
These approaches, designed to attenuate the deleterious
reductive decarbonylation, still only deliver intermolecular
hydroacylation catalysts that operate at relatively high loadings
of 5−10 mol %.4,36
A more refined approach to the development of catalysts that
operate at low loadings (ideally less than 1 mol %), and for a
wide range of substrates, would be to selectively increase the
rate of ketone reductive eliminationthe step that is accepted
to be rate-limiting for alkene hydroacylation. This could be
achieved sterically, by the use of bulky diphosphine ligands, or
electronically, by variation of the ligand bite-angle or inclusion
of electron-withdrawing substituents.8,37−40 However, within
the context of olefin hydroacylation with β-S-substituted
aldehydes, recent results using wide-bite-angle ligands such as
Ph2P(CH2)5PPh2 or sterically bulky ligands such as
(o-iPrC6H4)2P(CH2)2P(o-iPrC6H4)2 demonstrate that they are
not suitable for delivering linear-selective intermolecular alkene
hydroacylation. For example, while the overall rate of reaction
can be increased significantly with increasing bite-angle using
Ph2P(CH2)nPPh2 (n = 2−5), there are selectivity changes
between aldehyde versus alkene hydroacylation.13 Branched-
selective catalysis is favored over linear-selective when using the
sterically bulky ligand (o-iPrC6H4)2P(CH2)2P(o-iPrC6H4)2 in
alkyne hydroacylation.14 Use of the wide-bite-angle POP ligand
Xantphos results in irreversible oxygen coordination at the
rhodium center, giving an inactive acyl hydride.13
systems due to ring strain imposed by the chelate ring.47
Reductive elimination of H2 from [H2Rh(PP)2]+ complexes
(PP = chelating diphosphine) has also been shown to be heavily
influenced by the natural bite-angle of the diphosphines. Small-
bite-angle diphosphines favor Rh(I) complexes (i.e., reductive
elimination) [Rh(PP)2]+ while larger bite-angle diphosphines
favor Rh(III) complexes [H2Rh(PP)2]+.48,49
We were also encouraged by the report by Fink that
reductive elimination of ethane from {Cy2PCH2PCy2}PdMe2
was rapid, while complexes with longer chain chelates only
did so slowly.50 It was suggested that Pd−P dissociation of
one of the phosphine arms in this d8 system might lead to
rapid reductive elimination via a T-shaped intermediate,
although in other related d8 systems such intermediates have
been discounted on the basis of computational and NMR
spectroscopy studies.51 Small-bite-angle ligands based
upon R2PCH2PR2 and R2PNR′PR2 have also been success-
fully used in ethene oligomerizations mediated by chromium
catalysts, in which subtle variation of ligand electronics and
sterics leads to changes in selectivity.52 Although the
mechanism is very complex,53 controlling the rate of
reductive elimination of the final product (e.g., 1-hexene) is
implicit.
Here we report the development of new rhodium catalysts,
containing the small-bite-angle diphosphine ligands R2PCH2PR′2
t
(R, R′ = Bu, Cy) for the intermolecular hydroacylation of a
wide variety of unactivated alkenes and alkynes with β-S-
substituted aldehydes. Mechanistic studies indicate that,
through judicious choice of solvent and catalyst/substrate
concentration, both the decarbonylation and the productive
reaction can be tuned to such an extent that very low catalyst
loadings (0.1 mol %) and turnover frequencies of greater than
300 h−1 can now be achieved. Moreover, these catalyst systems
are readily prepared and bench-stable.
RESULTS AND DISCUSSION
■
Synthesis of the Diphosphine Catalyst Precursors. On
the basis of previous work on the stabilization of low coordinate
bis-phosphine rhodium(I) fragments using the weakly coordi-
nating fluorobenzene ligand,54−56 we targeted the synthesis of
[Rh(C6H5F)(R2PCH2PR′2)][BArF ] (1a, R = R′ = Cy; 1b, R =
4
t
t
Cy, R′ = Bu; 1c, R = R′ = Bu) as well-defined catalyst
precursors for these studies. These complexes were readily
prepared using a simple one-pot procedure involving addition
Mindful of these results, we turned to small-bite-angle
electron-rich ligands, R2P(CH2)PR′2, developed by Hoffmann
R, R′ = tBu or Cy41−43 (Scheme 2), in an effort to deliver both
of the diphosphine ligands to [Rh(COD)2][BArF ] (COD =
4
1,5-cyclooctadiene) in C6H5F solution and subsequent hydro-
genation (Scheme 3). Precipitation with pentane afforded 1a−c
as yellow microcrystalline solids with high isolated yields
(>70%). These three new complexes were fully characterized
by NMR spectroscopy, ESI-MS, and elemental microanalysis.
An important practical observation for these systems is that
they are air-stable and are able to be stored in vials on the
bench.
Scheme 2. Small-Bite-Angle Phosphine Ligands Used in This
Study
1
fast and selective catalysis. These ligands, with their compressed
P−M−P bite-angles, promote cis-geometries and low-coordinate
monomeric T-shaped Rh(I) RhL2X intermediates.41,44 As low-
coordinate intermediates are also necessary for reductive
elimination, especially in systems derived from 6-coordinate d6
metal complexes,45,46 we reasoned that similar complexes might
be accessible in the Rh(III) intermediates such as C using these
small-bite-angle ligands. Indeed, Werner has commented that
Rh(III) fragments of the type [Rh(iPr2PCH2PiPr2)]+ promote
reductive elimination reactions more readily than nonchelate
The room-temperature H NMR spectra of 1a−c in CD2Cl2
solution show characteristic, total integral 5H, upfield shifted
resonances for η6-coordinated fluorobenzene ligands (δ 6.0−
6.8, cf. δ 7.0−7.4 for free ligand). This coordination was also
demonstrated by 13C and 19F NMR spectroscopy, with the later
revealing coordinated fluorobenzene resonances at ca. δ −123
(cf. δ −113.9 for free ligand). Single 31P environments were
observed for 1a (δ −8.6) and 1c (δ 14.9), that show coupling
to 103Rh (1J(RhP) = 170 and 176 Hz, respectively). For 1b the
different 31P environments are observed at δ −12.7 and 17.9 as
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Scheme 3. Preparation of Diphosphine Catalyst Precursors 1a−c
doublets of doublets, with a 2J(PP) coupling constant of 83 Hz
and J(RhP) coupling constants of ca. 173 Hz. ESI-MS, which
used as the solvent. The DPEphos-ligated complex [Rh-
1
(DPEphos)(nbd)][BArF ] (3; nbd = norbornadiene), which
4
shows strong molecular-ion peaks with retention of fluoro-
benzene, and microanalysis confirm the empirical formulas.
Taken together, these data fully support the structures shown
for 1a−c.
has previously been shown to catalyze the hydroacylation of 1-
hexene or 1-octyne with 2,10 was used as a benchmark for these
reactions (Table 1). Catalyst 3 requires pretreatment with H2
to produce the active species, whereas 1a−1c were used
directly.
The solid-state structures of 1a−c have also been determined
by single crystal X-ray diffraction. That of 1c is shown in Figure 1,
The results in Table 1 demonstrate that 1a−c significantly
outperform 3 and are the most efficient catalysts reported to
date for these substrates. Within this manifold, certain catalysts
appear to perform better with different substrates: 1c is slightly
more effective for promoting the hydroacylation of 1-hexene
than 1a (94% versus 86%, respectively), while, for the
hydroacylation of 1-octyne, 1a is better than 1c (95% versus
90%). The precise reason(s) for these differences is currently
unresolved, but given the similar P−Rh−P bite-angles for these
catalysts, they most likely result from the steric profile of the
ligands. Consistent with this idea, the mixed phosphine catalyst
1b is intermediate in both rate and conversion between 1a and
1c for these hydroacylation reactions (Table 1). Despite the
much slower rate for the hydroacylation of nbd, compared to
1-hexene, high conversions are still achieved using the PCP-
catalysts (i.e., 96% for 1a). The slower rate is attributed to the
intermediate (reversible) formation of Rh(I) nbd-adducts, i.e.
Figure 1. Solid-state structure of 1c; displacement ellipsoids depicted
at the 50% probability level. One of the two independent molecules in
the asymmetric unit is shown. Hydrogen atoms, anion, and disordered
[Rh(nbd)(R2PCH2PR′2)][BArF ]. For 3, we suggest that nbd is
4
too strongly bound to allow hydroacylation to occur.
t
components (C6H5F ligand, two Bu groups) omitted for clarity. Key
A time course plot of the hydroacylation of 1-hexane using
1a, 1c, and 3 (conversions determined using HPLC) is shown
in Figure 2. These data show that both PCP-catalysts have
considerably faster initial rates than 3, but they appear to
deactivate (presumably via reductive decarbonylation, vide
infra) over time. We discount significant product inhibition is
occurring, as addition of 50 mol % of ((o-methylthio)phenyl)-
nonan-1-one (the ketone product of octene hydroacylation
with 2) to the initial catalytic mixture resulted in only a small
reduction in overall conversion when using 1c.
bond lengths (Å) and angles (deg): Rh1−P1, 2.263(2); Rh1−P2,
2.2711(15); Rh1−C, 2.298(4)−2.341(4); P1−Rh1−P2, 74.57(5);
P1−C7−P2, 95.7(3); Rh2−P11, 2.2591(15); Rh2−P12, 2.2546(15);
Rh2−C, 2.22(3)−2.36(4); P11−Rh2−P12, 74.44(5); P11−C107−
P12, 95.1(3).
with the others given in the Supporting Information. A closely
related compound to 1c featuring the more coordinating benzene
ligand has previously been reported, [Rh(C6H6)-
(tBu2PCH2PtBu2)][BF4].57 These four structures show compara-
ble geometries and, correspondingly, similar structural metrics.
Although in the structures of 1a−c, the fluorobenzene ligands are
disordered, all clearly demonstrate the η6-coordination of the
arene to the metal center with Rh−C distances, e.g. 2.22(3)−
2.36(4) Å in 1c, being similar to those in other fluorobenzene
Rh(I) complexes, viz. [Rh(Ph2P(CH2)2PPh2)(C6H5F)][BArF ]
Encouraged by the very fast hydroacylation rates observed
using the small-bite-angle diphosphine ligands, we next
investigated the organometallic chemistry and the resulting
t
catalytic pathways in greater detail. We selected the Bu
substituted complex 1c, as this provided a good combination of
1
a fast rate of catalysis and ease of solution H and 31P NMR
(2.292(4)−2.377(4) Å)56 and [Rh(PiBu3)2(C6H5F)][BArF4]
characterization.
4
(2.299(9)−2.411(7) Å).55 The diphosphine bite-angles in 1a
and 1b are the same within error, viz. 72.78(3)° and 72.86(3)°,
respectively, although they are slightly smaller in comparison to
those for 1c [74.57(5)°, 74.44(5)° (Z′ = 2)] and [Rh(C6H6)-
(tBu2PCH2PtBu2)][BF4] (74.29°).57
Model Complexes Using 2-(Diphenylphosphino)-
benzaldehyde. The reaction of 1c with the phosphine
tethered aldehyde 2-(diphenylphosphino)benzaldehyde was
first investigated. This aldehdye has previously been employed
in hydroacylation reactions in combination with rhodium
catalysts,58,59 but the strongly coordinating nature of the phos-
phine tether necessitates the use of forcing reaction conditions
to promote turnover. However, this stability lends itself to the
ability to characterize stable model complexes. Addition of
2-(diphenylphosphino)benzaldehyde to 1c in d6-acetone
at room temperature resulted in rapid cyclometalation60
Catalyst EvaluationIntermolecular Hydroacylation.
With the PCP-catalysts 1a−c in hand, we evaluated their
activity in three simple, but relatively challenging, intermole-
cular reactions: the hydroacylation of 1-hexene, norbornadiene,
and 1-octyne, all with 2-(methylthio)benzaldehdye (2).
Catalyst loadings were 10 mol %, and dichloroethane was
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a
Table 1. Screening of 1a−c and 3 as Alkene and Alkyne Hydroacylation Catalysts
a
b
c
Conditions: aldehyde (1.0 equiv, 0.075 M), alkene, or alkyne (1.5 equiv), 10 mol % catalyst, ClCH2CH2Cl, 353 K. Isolated yield. Catalyst was
d
e
pretreated with hydrogen. 298 K. Linear: branched ratio 10:1; at 353 K, 93% yield after 2 h as a 2:1 L/B ratio.
complexes with the small-bite-angle ligands R2PCH2PR2 have
been reported previously.47,61 Together these NMR data in-
dicate that the phosphine and acyl groups lie coplanar, with the
hydride ligand in an axial position in a similar way to that found
10
for [Rh{κ2(P,P)-DPEphos}(MeSC6H4CO)H(MeCN)]+ but,
interestingly, different from that in [Rh(o-iPrC6H4)2P(CH2)2
P(o-iPrC6H4)2(MeSC6H4CO)H]+, where the hydride is trans to
a phosphine and the acyl trans to the vacant site.14 We suggest
the coordination sphere in 4 is completed by weak coordination
of an acetone ligand trans to the hydride ligand, as the hydride
chemical shift of δ −19.4 does not reflect a trans vacant site.62
Complex 4 is stable in d6-acetone solution, and no significant
1
changes are observed by H and 31P NMR spectroscopy after
5 days in solution at 298 K. This is in contrast to the equivalent
complex of aldehyde 2, in which reductive decarbonylation
occurs relatively rapidly (vide infra). The acetonitrile adduct
[Rh(tBu2PCH2PtBu2)H{κ2(P,C)-PPh2(C6H4CO)}(NCMe)]-
Figure 2. Time course plot for the hydroacylation of 1-hexene (1.5
■
▲
equiv) with 2 (1.0 equiv, 0.075 M) catalyzed by 1c ( ), 1a ( ), or
●
3 ( ). Conditions: 10 mol % catalyst, ClCH2CH2Cl, 353 K.
[BArF ] (5) can be formed on addition of excess acetonitrile to
4
4 (Scheme 4).63 Addition of ethylene to 4 at room temperature
(less than 5 min) and formation of the acyl hydride complex
resulted in the slow formation of [Rh(tBu2PCH2PtBu2)-
[Rh(tBu2PCH2PtBu2)H{κ2(P,C)-PPh2(C6H4CO)}(OCMe2)]-
{κ2(P,O)-PPh2(C6H4COEt)}][BArF ] (6) over a period of
[BArF ] (4) quantitatively by NMR spectroscopy (Scheme 4).
4
4
12 h (Scheme 5). Complex 6 is the rhodium(I) adduct of the
product of ethylene hydroacylation with 2-(diphenylphosphino)-
benzaldehyde. This reaction has been reported previously under
catalytic conditions, using [Rh(COD)Cl]2 as a catalyst, with both
ethene and 1-hexene, but the organometallic intermediates were
not reported.58
These model complexes provide a firm spectroscopic footing
to study those formed with the more weakly coordinating
thioether functionalized aldehyde 2-(methylthio)benzaldehyde
(2), which we now discuss.
The formation of 4 is readily apparent from NMR spectroscopy
(Supporting Information). In particular, a relatively sharp high
field doublet of apparent quartets at δ −19.4 is observed in the
1H NMR spectrum, while the 31P{1H} NMR spectrum (250 K)
shows three well-resolved doublet of doublet of doublets
(AHPX spin system) at δ 57.9, 30.8, and 9.8. All the phosphine
environments show coupling to 103Rh, although the magni-
tude of coupling to PB is significantly reduced in comparison
(1J(RhP) = 47 Hz, cf. 126 and 113 Hz), consistent with its
coordination opposite a high trans-influence acyl ligand. Similar
magnitudes for 103Rh coupling have been observed in other trans
acyl Rh-chelate phosphine complexes,10,14,47,61 while Rh-acyl
Characterization of Intermediates Using Aldehyde 2.
Addition of aldehyde 2 to a CH2Cl2 solution of 1c results
in the initial formation of the Rh(I) aldehyde adduct
Scheme 4. Formation of Acyl Hydride Complexes 4 and 5
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Scheme 5. Addition of Ethylene to Acyl Hydride Complex 4
[Rh(tBu2PCH2PtBu2){κ2(S,O)-SMe(C6H4CHO)}][BArF ]
4
(7), which proceeds to give [Rh(tBu2PCH2PtBu2)(CO)-
(SMePh)][BArF ] (8), the product of reductive decarbonylation
4
(Scheme 6). No acyl hydride intermediate was observed. These
two processes have been modeled using a two-step first-order
kinetic model (Supporting Information), in which formation of
7 and 8 occur with rate constants of (1.59 0.02) × 10−4 s−1 and
(1.75 0.03) × 10−4 s−1 respectively (t1/2 = 1.10 0.02 h).
Compound 7 was characterized in situ, while 8 could be
isolated in good yield as a microcrystalline yellow solid. NMR
data for 7 and 8 are fully consistent with their formulation. In
particular, both show inequivalent, mutually coupled, 31P
Figure 3. Solid-state structure of 8; displacement ellipsoids depicted at
the 50% probability level. Most hydrogen atoms, anion, and disordered
components (Ph group) omitted for clarity. Key bond lengths (Å) and
angles (deg): Rh1−P1, 2.2779(7); Rh1−P2, 2.3719(7); Rh1−C1,
1.867(3); Rh1−S1, 2.3797(8); P1−Rh1−P2, 74.36(2); P1−C9−P2,
98.23(12); P1−Rh1−C1, 94.50(10); P2−Rh1−C1, 168.69(10); C1−
Rh1−S1, 96.15(10); P1−Rh1−S1, 168.79(3); P2−Rh1−S1, 95.09(3);
Lsq plane (Rh1, P1, P2, S1, C1), rms deviation = 0.047.
1
environments to a Rh(I) center. Furthermore, the H NMR
spectrum of 7 shows the coordinated aldehyde at δ 9.47 (cf.
free 2 δ 10.3) and bound thioether at δ 2.63 (cf. free 2 δ 2.49).
The solid-state structure of 8 has been determined (Figure 3)
and is fully consistent with the solution NMR data. The bond
metrics for the coordinated thioether are similar to those
reported for the decarbonylation product for the same aldehyde
from the DPEphos system [Rh(κ2(P,P)-DPEphos)(CO)-
(SMeEt)][CB11H6I6].10 Notably, the Rh−P distances trans to
the carbonyl are longer than that trans to the thioether
[2.3719(7) and 2.2779(7) Å, respectively], consistent with the
differing trans influences of these ligands. To put the
characterization of 7 on a firm footing, we have also prepared
the stable ketone analogue, [Rh(tBu2PCH2PtBu2)(κ2(S,O)-
[Rh(tBu2PCH2PtBu2)(OCMe2)2][BArF ] (10) (1c/10 = 1:6.5
4
at 0.015 M and 298 K). Adding 1.5 equiv of aldehyde 2 to this
mixture resulted in a new equilibrium mixture containing 1c,
10, 7, and the acyl hydride [Rh(tBu2PCH2PtBu2)H{κ2(S,C)-
SMe(C6H4CO)}(OCMe2)][BArF ] (11). Although the relative
4
concentration of these species changes with temperature,
demonstrating dynamic equilibrium (Scheme 7), over all
temperatures 11 is the major species present. Reversible
oxidative addition of aldehyde 2 has been observed previously
in the [Rh(o-iPrC6H4)2P(CH2)2P(o-iPrC6H4)2)]+ system14 as
well as in other hydroacylation systems.6,8,12 Complex 11 was
characterized in situ by NMR spectroscopy and also by
comparison with the relatively stable MeCN adduct analogue
(vide infra). At room temperature for 11, broad resonances are
observed for the methylene and tBu protons as well as a hydride
MeCOC6H4SMe)][BArF ] (9) (Scheme 6) by addition of 2-
4
(methylthio)acetophenone to 1c, which has very similar NMR
spectroscopic data to that of 7.
An acyl hydride intermediate was not observed in CH2Cl2,
presumably because this putative 5-coordinate species rapidly
undergoes carbonyl deinsertion and reductive elimination to
form 8, a process that would be slowed by blocking the
sixth coordination site. With DPEphos (or related ligands),
this is achieved by coordination of the central oxygen atom.10,13
Such stabilization is not possible in these small-bite-angle
systems. Instead, we reasoned that changing the solvent
to acetone could provide stabilization for the acyl hydride
intermediate. Dissolving 1c in acetone results in an equilib-
rium being established between 1c and the bis-acetone adduct
1
signal at δ −20.29 in the H NMR spectrum. Two broadened
environments are observed in the 31P NMR spectrum. At 210 K
these two 31P environments are sharp and display very different
coupling to 103Rh, δ 36.2 (1J(RhP) = 131) and 9.4 (1J(RhP) =
57), consistent with a Rh(III) center and the different trans-
influence of thioether over acyl, respectively. These data are
similar to those for 4 and 5. The hydride signal in the 1H NMR
spectrum at this temperature is also sharp and is observed at
δ −20.18 as a doublet of doublet of doublets that collapses to a
doublet in the 1H{31P} NMR spectrum. Four environments are
Scheme 6. Reactivity of 1c in CH2Cl2
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a
Scheme 7. Reaction of 1c with 2 in d6-Acetone
a
1
Composition determined using H and 31P{1H} NMR spectroscopy; error estimated to be 5%.
Scheme 8. Reactivity of MeCN-Ligated Complexes with 2
t
31P{1H} NMR spectra of 13 are similar to those of 11 and also
show that bound MeCN exchanges with the bulk solvent, as
only a broad resonance is observed at δ 2.0 for free and bound
MeCN. As for 4 and 5, the hydride resonance in 13 is found at a
higher frequency than that in 11 (δ −15.6), reflecting the
stronger binding of MeCN compared to acetone.62 Despite the
straightforward solution synthesis of 13, attempts to this isolate
this compound in the solid state were frustrated by the rapid loss
of MeCN at room temperature (under vacuum or argon), leading
to a mixture of products, including 7 and 8. A single crystal was,
however, able to be grown from a CH2Cl2/hexane solution at
5 °C and rapidly transferred into the cold stream of an X-ray
diffractometer, allowing for structural characterization (Figure 4).
The structural metrics reflect the differing trans influences of acyl
over thioether, viz. Rh1−P1 2.4545(8) Å versus Rh1−P2
2.3063(8) Å. These distances are similar to those seen in the
closely related Rh(III)−acyl complexes of DPEphos ligands, as is
the Rh−S distance [2.3612(9) Å].10
now observed for the Bu protons and two for the methylene
protons on the phosphine backbone. At low temperature, the
SMe group is observed as a doublet at δ 2.66, showing coupling
to 31P{1H} that collapses to a singlet in the H{31P} NMR
1
spectrum.
This equilibrium mixture changes with time, reflecting the
irreversible formation of the decarbonylation product 8. The
formation of 8 follows first-order reaction kinetics with a rate
constant of (1.08 0.04) × 10−4 s−1 (t1/2 = 1.79 0.06 h), and
the reaction proceeds to completion after 10 h. This rate is
slower than that for the same reaction in CH2Cl2 [t1/2 = (1.10
0.02 h)]. The stabilizing role of acetone is also apparent through
the observation of the acyl hydride intermediate 11 in this
solvent, in contrast to CH2Cl2. Repeating the reaction with a 5-
fold excess of 2 gave a 7/11 ratio of 1:1.30 at 298 K. Under these
conditions, the formation of 8 again followed first-order reaction
kinetics with the same rate within error (0.94 0.03) × 10−4 s−1
(t1/2 = 2.02 0.07 h), consistent with a first-order process from
11, i.e. one independent of [2].
Although the MeCN ligand is labile through exchange with
bulk solvent, it is strongly enough bound to attenuate
decarbonylation appreciably. Decarbonylation to form 8 occurs
spontaneously at 298 K from equilibrium mixtures of 12c and
13. Following this reaction (starting with 12c/13 = 1:3.1)
revealed first-order reaction kinetics for the formation of 8, with
a rate constant of (5.1 0.3) × 10−6 s−1 (t1/2 = 38 2 h). This
is markedly slower in comparison to the decarbonylation
reactions in acetone and CH2Cl2, although it is more rapid than
the analogous DPEphos system, in which oxygen coordinates
In an attempt to isolate the acyl hydride intermediate cleanly,
we added a stronger Lewis base, MeCN, as we have previously
shown10 that MeCN can stabilize such intermediates. Addition
of a five-fold excess of MeCN at 298 K to the freshly prepared
acetone equilibrium mixture resulted in the immediate
formation of a mixture of the bis-acetonitrile Rh(I) adduct
[Rh(tBu2PCH2PtBu2)(MeCN)2][BArF ] (12c) and the acyl
4
hydride complex [Rh(tBu2PCH2PtBu2)H{κ2(S,C)-SMe-
(C6H4CO)}(NCMe)][BArF ] (13) in a 1:1.2 ratio (Scheme 8).
4
[(1.2
0.1) × 10−6 s−1 (t1/2 = 160
12 h)].54 This later
To facilitate the unambiguous characterization of these species,
12c was prepared by reaction of 1c with MeCN. The cyclohexyl
observation is related to the relative availability of the vacant
site (O-decoordination in a chelate versus NCMe loss).
To further investigate the stabilizing effect of nitrile-based
ligands against decarbonylation, we next targeted the incorporation
of commercially available [NCCH2BF3]− anion into the metal
coordination sphere, hoping to exploit additional Coulombic
anion−cation interactions. This anion was originally reported
analogue [Rh(Cy2PCH2PCy2)(MeCN)2][BArF ] (12a) was
4
also prepared in the same way. Addition of 2 to isolated 12c
also resulted in equilibrium mixtures of 12c and 13. When
1.5 equiv of 2 was added at 298 K, the ratio of these two species
was 1:3.0, whereas addition of 5 equiv of 2 gave a ratio of
1:19.0allowing definitive characterization of 13. The H and
1
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23.7 (dd, 1J(RhP) = 124, 2J(PP) = 43, 1P), −11.4 (dd, 1J(RhP) =
105, 2J(PP) = 43, 1P) (ca. 25%) and δ 20.1 (dd, 1J(RhP) = 102,
2J(PP) = 31, 1P), −6.0 (dd, 1J(RhP) = 108, 2J(PP) = 31, 1P) (ca.
15%) but remain unassigned.
Comments on Decarbonylation. Table 2 summarizes the
decarbonylation data assembled from these studies. The rates of
decarbonylation decrease in the order 7 (CH2Cl2) > 11 ≫ 13 >
17, with no significant decarbonylation observed for 4. As these
relate to the stability of the [Rh(tBu2PCH2PtBu2)H{κ2(S,C)-
SMe(C6H4CO)}]+ fragment, there is a clear correlation
1
between increased donor strength (as indicated by H NMR
shifts of the trans-hydride, where available) and the attenuation
of decarbonylation, with CH2Cl2 providing the weakest
stabilization and the anionic nitrile [NCCH2BF3]− the
strongest. That an acyl hydride is not observed in CH2Cl2
solution at all is consistent with rapid decarbonylation from the
putative five-coordinate species in the absence of Lewis bases.
The observation that 4 does not decarbonylate, while directly
analogous 11 does, suggests that dissociation of the Rh−E bond
(E = S or P), or steric constraints imposed by the PPh2 group
in the ring, are also important, as acetone dissociation would be
expected to occur in both to form a vacant site. This further
emphasizes that a balance must be struck between stabilization
and reactivity in the onward hydroacylation reaction, as too
strong a coordination will result in no reaction, albeit with no
decarbonylation.13
Figure 4. Solid-state structure of 13; displacement ellipsoids depicted
at the 50% probability level. Most hydrogen atoms and anion omitted
for clarity. Key bond lengths (Å) and angles (deg): Rh1−P1,
2.4545(8); Rh1−P2, 2.3063(8); Rh1−C1, 2.024(3); Rh1−S1,
2.3612(9); Rh1−H0, 1.46(3); Rh1−N1, 2.137(3); P1−Rh1−P2,
74.49(3); P1−C11−P2, 101.08(15); P1−Rh1−C1, 169.07(9); P2−
Rh1−C1, 95.16(9); C1−Rh1−S1, 85.15(10); P1−Rh1−S1,
103.21(3); P2−Rh1−S1, 158.78(3); H0−Rh1−N1, 171.0(13); Lsq
plane (Rh1, P1, P2, S1, C1), rms deviation = 0.180.
by Molander in 2006,64 and to our knowledge, there is no
coordination chemistry reported for it. Formation of a suitable
rhodium precursor incorporating this anion was achieved
by addition of hydrogen to the bis-rhodium salt [Rh-
(tBu2PCH2PtBu2)(NBD)][Rh(tBu2PCH2PtBu2)(NCCH2BF3)2]
(14) in the presence of excess cyclooctene. This resulted in the
formation of [Rh(tBu2PCH2PtBu2)(C8H14)(NCCH2BF3)] (15),
which was isolated as an orange−yellow powder (Scheme 9).
Dissolution of 15 in acetone cleanly forms the monoacetone
adduct, 16, which reacts with excess 2 to form the zwitterionic
acyl hydride [Rh(tBu2PCH2PtBu2)H{κ2(S,C)-SMe(C6H4CO)}-
(NCCH2BF3)] (17) in quantitative yield (Scheme 10). Com-
plex 17 was characterized by NMR spectroscopy and a single-
crystal X-ray diffraction study (Figure 5). NMR data are in full
accord with its formulation and are very similar to those for 11
and 13. The structural metrics are unremarkable and show
coordination of the [NCCH2BF3]− anion trans to the hydride.
Dissolving pure 17 in acetone solvent established an
equilibrium with 16/free 2 (1:0.25, 0.015 M), further
demonstrating reversible oxidative addition of aldehyde 2 in
these small-bite-angle diphosphine complexes.
Comments on the Overall Mechanism. Monitoring the
catalytic hydroacylation of 1-octene with 2 using 10 mol % 1c
in d6-acetone (0.075 M substrate) by NMR spectroscopy at 298 K
showed the complete and pseudo-first-order formation of the
linear ketone product with a rate constant of (2.0
0.2) ×
10−3 s−1 (t1/2 = 5.8 0.6 min). Notably, this rate is consider-
ably faster than decarbonylation of 11 in acetone at this
temperature (1.08 0.04) × 10−4 s−1. During and at the end of
catalysis, the only observed species was the product-bound complex
that arises from reductive coupling [Rh(tBu2PCH2PtBu2)-
{MeSC6H4CO(CH2)7Me}][BArF ] (18), as indicated by
4
NMR spectroscopy, ESI-MS, and independent synthesis from
isolated product and 1c. The decarbonylation product, 8, was
only observed in trace amounts by ESI-MS. Thus, under these
conditions (10 mol % catalyst, acetone), productive catalysis
clearly outruns decarbonylation. Repeating this catalytic
experiment using 2-(methylthio)benzaldehdye-d1 (d1-2) re-
sulted in slower overall catalysis. A H/D kinetic isotope effect
(KIE) value of 1.5 0.3 was measured. Similarly, a KIE value of
1.3 0.3 was obtained from an initial rate study using 1 mol %
1c in acetone (0.075 M substrate) at 328 K, where conversions
were determined using HPLC (see Supporting Information).
In the presence of a slight excess of 2 (1.5 equiv/Rh), 17 is
relatively stable in solution, undergoing a slow first-order
decomposition with a rate constant of (2.7 0.3) × 10−6 s−1
(t1/2 = 73 9 h), significantly slower than those observed for
11 (t1/2 = 1.79 0.06 h) and 13 (t1/2 = 38 2 h). A mixture of
at least three organometallic species is observed after 10 days in
solution: the major cationic species is 8 (ca. 60%) by 31P NMR
spectroscopy. The other species show pairs of resonances at δ
1
2
Moreover, inspection of the H and H NMR spectra of the
final product obtained from catalysis using d1-2 show that
deuterium is incorporated into methylene positions both α
and β to the ketone carbonyl (Scheme 11), at δ 2.95 and 1.72,
respectively, in a 1:4 ratio. That only the linear isomer of the
ketone is observed as the final product to the detection limits of
HPLC (i.e., a ratio of greater than 20:1 linear to branched)
Scheme 9. Synthesis of [NCCH2BF3]− Ligated Complexes
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Scheme 10. Reactivity of [NCCH2BF3]− Ligated Complexes with 2
branched alkyl intermediates (intermediates C and B Scheme 11),
but reductive elimination for the linear isomer has a considerably
lower barrier.8 ESI-MS demonstrates that there is a small amount
of the d0-product that could arise from β-elimination of a hydride
to give A followed by alkene exchange.65 Reversible hydride
insertion has been noted previously.6,8 Although linear selectivity is
by far the most common in intermolecular hydroacylation systems
using [Rh(diphosphine)]+ catalysts,4 we have recently noted that
sterically bulky ortho-substituted dppe-derived phosphines can
direct excellent branched selectivity in alkyne hydroacylation.14
Rate-limiting reductive elimination of the final product would
be expected to result in a negligible KIE, as no C−H bonds are
being made or broken. Dong has recently reported a KIE of
1.79
0.06 for intramolecular aldehyde hydroacylation, and
when coupled with a Hammett study, suggested that this is due
to the hydride insertion step being rate-limiting, rather than
reductive elimination.12 The oxidative addition of aldehydes on
closely related cationic [Rh(dppp)]+ systems has been shown
to have a KIE of 1.73 for phenylacetaldehyde, where migratory
extrusion of CO is rate-determining,66 while van Leeuwen and
co-workers have shown that a small KIE of 1.22 0.11 relates
to the hydride migration step in the hydroformylation of
1-octene using Rh-Xantphos complexes, although they also note
that CO dissociation and alkene coordination also contribute to
the overall barrier.67 Interestingly, a recent report by Hofmann
and co-workers shows that for neutral Rh(tBu2PCH2PtBu2)-
(Np)(η2-H2CCH2) (Np = neopentyl) the barrier to alkyl
migration is also high, such that this complex can be isolated
and characterized in the solid-state (albeit at low temperature).68
Figure 5. Solid-state structure of 17; displacement ellipsoids depicted
at the 50% probability level. Most hydrogen atoms and solvent
molecules are omitted for clarity. Key bond lengths (Å) and angles
(deg): Rh1−P1, 2.4626(11); Rh1−P2, 2.3264(10); Rh1−C1,
2.031(4); Rh1−S1, 2.3354(11); Rh1−H0, 1.61(4); Rh1−N1,
2.141(4); P1−Rh1−P2, 73.92(4); P1−C11−P2, 101.03(19); P1−Rh1−
C1, 165.33(12); P2−Rh1−C1, 97.69(12); C1−Rh1−S1, 85.84(12); P1−
Rh1−S1, 99.92(4); P2−Rh1−S1, 167.37(4); H0−Rh1−N1, 170.1(14);
Lsq plane (Rh1, P1, P2, S1, C1), rms deviation = 0.097.
indicates that insertion of the hydride (deuteride) into the
alkene is reversible and is occurring to give both linear and
a
Table 2. Relative Rates for the Formation of 8 from [Rh(tBu2PCH2PtBu2){SMe(C6H4CHO)}(L)]+
a
b
Rates reported for the first-order formation of 8. Other products in addition to 8 are formed. The rate of acyl hydride decomposition is reported
instead.
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Scheme 11. Suggested Catalytic Cycle for the Hydroacylation of Alkenes with 2
In our system, given the equilibria observed in both the stoi-
chiometric studies and by deuterium labeling in catalysis, an
“equilibrium isotope effect”69 may also be operating. This means
that the measurement of a small KIE ∼ 1.4 in our system points
only to irreversible oxidative addition not being a rate-limiting
step, as this would be expected to result in a significant KIE.
Scheme 11 summarizes our mechanistic interpretations.
Effect of Solvent and Concentration. Having established
the overall rapid turnover of these small-bite-angle catalysts,
that acyl hydrides are intermediates, and that decarbonylation
follows a first-order process and can be attenuated to differing
degrees by various Lewis bases, we next looked to bring these
observations together to optimize the conditions for the
intermolecular hydroacylation reaction. For this we used the
reaction between aldehyde 2 and 1-octene. Table 3 outlines these
studies.
At 10 mol % and 0.075 M aldehyde concentration (e.g.,
Figure 2), catalyst 1c performed very well in dichloroethane
solvent, outperforming the DPEphos catalyst 3 (entries 1
and 2). Reducing the catalyst loading to 1 mol % resulted in a
significant drop in conversion, presumably as a consequence of
decarbonylation (entry 4, Figure 6). ESI-MS of the postcatalyst
solution confirmed this, with all the major peaks observed being
attributed to carbonyl containing species, including 8 (see
Supporting Information). Addition of more substrate to the
postcatalysis solution resulted only in a small additional
conversion (∼10%) in the first hour and then no more.
Addition of small quantities of MeCN (ca. 2 equiv, entry 5)
improved slightly the overall conversion using 1c, as anticipated
from the stoichiometric decarbonylation studies. However,
catalysis in the presence of excess MeCN (greater than 2 equiv)
attenuated catalysis (entries 6 and 7), presumably as the added
MeCN increasingly outcompetes alkene coordination. Sim-
ilarly, employing 15, containing the strong binding anionic
nitrile ligand, resulted in reduced conversion compared to 1c.
Using the preformed bis-acetonitrile complex 12c (entry 8)
gave the best improvement in comparison to 1c. It is interesting
to note that, in related zwitterionic Rh(I)−ligand complexes,
intramolecular hydroacylation reactions can be run in neat
MeCN.21
Changing solvent from dichloroethane to acetone demon-
strated the stabilizing effect of the latter. Using both 1c and
12c, high conversions were achieved (e.g., entries 11 versus 3;
Figure 7), with 12c again giving the best results. Conversion
using the DPEphos catalyst was also improved, but was still low
(12 %). The effect of solvent (ClCH2CH2Cl versus acetone) is
greater than that of added MeCN (entries 4/11 and 4/8,
respectively; Figures 6 and 7), although both the effects are
additive (entry 12). In addition to stabilization against
decarbonylation, a recent computational analysis for the
intramolecular hydroacylation of 4-pentenals using Rh(I)-
dppe catalysts has suggested that Lewis bases (i.e., acetone/
MeCN in our systems) can also play a role in reducing the
barrier to reductive elimination.11 Whatever the subtleties of
the actual mechanism are here, our data show that the complex
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a
Table 3. Catalyst Optimization
a
Conditions: ClCH2CH2Cl solvent, 353 K; acetone solvent, 328 K. Aldehyde (1.0 equiv) and alkene (1.5 equiv). Concentration refers to the
concentration of aldehyde 2. Conversions and selectivity are by HPLC. Linear isomer found in a greater than 20:1 ratio compared to the branched.
Figure 6. Time course plot for the hydroacylation of 1-octene (1.5
Figure 7. Time course plot for the hydroacylation of 1-octene (1.5
equiv) with 2 (1.0 equiv, 0.075 M) catalyzed by 1c ( ) or 12c ( ).
Conditions: 1 mol % catalyst, acetone, 328 K.
◆
■
equiv) with 2 (1.0 equiv, 0.075 M) catalyzed by 1c ( ) or 12c ( ).
◆
■
Conditions: 1 mol % catalyst, ClCH2CH2Cl, 353 K.70
using the preformed MeCN complex 12c in acetone solvent
results in the best catalyst at 1 mol % loadings.
reactions (ca. 10 mol %). Entry 19 shows that for 12c 60%
conversion could be achieved at 0.5 M aldehyde and 0.1 mol %.
Using even more concentrated solutions (2.0 M aldehyde)
improved this further and resulted in quantitative conversion at
0.1 mol % loading using either 1c or 12c as catalyst precursors
(entry 21 and 22). These conversions correspond to turnover
frequencies of at least 300 h−1 (unoptimized). The limit of the
system was reached at 0.02 mol % (entry 23) with regard to a
practicable and productive catalyst.
Demonstration of Reaction Scope. With effective
catalysts in hand that operate at low loadings, we explored
the scope of their application in intermolecular hydroacylation
reactions, especially with substrates that have previously proved
difficult to employ (Table 4). We have used both
In an effort to improve the performance of our catalysts
further, we recognized that, as we had found decarbonylation to
be independent of substrate concentration whereas for
productive catalysis this was unlikely to be the case, increasing
the overall substrate concentration could kinetically favor
productive catalysis over decarbonylation. Pleasingly, this was
the case, and entry 16 shows that at 1 mol % loading and 0.5 M
aldehyde concentration essentially quantitative conversion was
achieved using catalyst 12c. 1c also worked well (entry 15).
Encouraged by these results, we looked to push the loadings to
even lower levels of 0.1 mol %, which represent 2 orders of
magnitude lower loadings than usually employed in these
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a
Table 4. Scope of Alkene and Alkyne Hydroacylation Using 12a and 12c
a
b
Conditions: Aldehyde (1.0 equiv, 2.0 M), alkene, or alkyne (1.5 equiv), catalyst, acetone, 328 K, 3 h. Linear isomers isolated with >20:1 selectivity
c
d
(HPLC) in all cases, accept where stated otherwise. Reaction performed at 353 K in ClCH2CH2Cl. 1.1:1 mixture of branched and linear isomers.
tBu2PCH2PtBu2 (12c) and Cy2PCH2PCy2 (12a) based bis-
sequence to give the dihydropyran product. Importantly, em-
ploying these new catalysts has allowed the hydroacylation of
more challenging substrates to be achieved. Disubstituted
alkenes are significantly less reactive substrates in hydroacyla-
tion reactions; using DPEphos-catalyst 3 at 10 mol %, the hydro-
acylation of methyl methacrylate shows no detectable product
after 18 h. However, using catalyst 12a, both 1,1-disubstituted
acetonitrile complexes to do this.
Using aldehyde 2, the hydroacylation of several unactivated
terminal alkenes was achieved using catalyst 12c at 0.1−0.2 mol %
loadings (entries 1−5). An interesting solvent effect was ob-
served when the hydroacylation of 3-buten-1-ol was performed
in DCE (entry 3), resulting in a cyclization/dehydration
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and 1,2-disubstituted alkenes (entries 6 and 7) could be readily
incorporated in 3 h. The hydroacylation of allenes provides easy
access to β,γ-unsaturated ketones;71 cyclohexylallene was
hydroacylated with aldehyde 2 using 2 mol % of catalyst 12a
(entry 8). Butyl vinyl ether could also be hydroacylated using
1 mol % of 12a to give a mixture of branched and linear isomers
(entry 9). To our knowledge, this is the first example of the
intermolecular hydroacylation of an enol ether.72 These reactions
clearly demonstrate the broad scope of alkene, alkyne, and allene
substrates offered by these catalysts.
The aldehyde substrate could also be varied. Both electron
rich (entry 10) and electron poor (entry 11) aryl aldehydes
were incorporated with only 0.2 mol % of catalyst 12c. A
cyclohexene aldehyde (entries 12 and 13) underwent efficient
hydroacylation of both alkyne and alkene substrates. Aliphatic
aldehydes were also useful substrates, and they proceeded well
in the hydroacylation of an alkene (entry 14) with 0.5 mol % of
12c and an alkyne (entry 15) with 1% of 12a. Finally, MTM-
protected hydroxyacetaldehyde (entry 16) underwent alkyne
hydroacylation with 2 mol % of 12a. We have recently demon-
strated the synthetic utility of the MTM protecting group as a
removable directing group for hydroacylation, although catalyst
loadings of 10 mol % have previously been required.33
ACKNOWLEDGMENTS
■
The EPSRC (Grant EP/G056609/1) for funding and Professor
Guy Lloyd-Jones for insightful discussions.
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CONCLUSIONS
■
We have outlined the development of new intermolecular
hydroacylation catalysts based upon small-bite-angle ligands
which allow for the union of β-S-substituted aldehydes with a
wide variety of unactivated alkenes and alkynes. Through
judicious choice of solvent and catalyst/substrate concen-
tration, the unwanted decarbonylation deactivation pathway is
attenuated while the productive hydroacylation reaction is
enhanced to such an extent that very low catalyst loadings (0.1
mol %) and turnover frequencies of greater than 300 h−1 can be
achieved. As these precatalyst systems are also readily prepared
and bench-stable, they offer a practical solution for carrying out
intermolecular hydroacylation reactions with β-tethered
aldehydes. The high activity of these catalysts has also allowed
previously challenging substrate classes to be included.
Interestingly, high enantioselectivies have previously been
reported in Rh-mediated hydrogenations using asymmetric
ligands closely related to tBu2PCH2PtBu2,73 and this encourages
further development given the low loading and high-turnovers
we report. With such efficient catalysts in hand the next
challenge is to develop systems that do not require a
β-tethered aldehyde.
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ASSOCIATED CONTENT
* Supporting Information
■
S
Full synthetic, crystallographic, and characterization details.
This material is available free of charge via the Internet at
http://pubs.acs.org. Crystallographic data have been deposited
with the Cambridge Crystallographic Data Centre under
CCDC Nos. 857099−857104. These data can be obtained
free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
AUTHOR INFORMATION
Corresponding Author
andrew.weller@chem.ox.ac.uk; michael.willis@chem.ox.ac.uk
■
Notes
The authors declare no competing financial interest.
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Journal of the American Chemical Society
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