D 2-symmetric dirhodium catalyst derived from a 1,2,2-triarylcyclopropanecarboxylate ligand: Design, synthesis and application

Article abstract of DOI:10.1021/ja2074104

Dirhodium tetrakis-(R)-(1-(4-bromophenyl)-2,2- diphenylcyclopropanecarboxylate) (Rh₂(R-BTPCP)₄) was found to be an effective chiral catalyst for enantioselective reactions of aryl- and styryldiazoacetates. Highly enantioselective cyclopropanations, tandem cyclopropanation/Cope rearrangements and a combined C-H functionalization/Cope rearrangement were achieved using Rh₂(R-BTPCP)₄ as catalyst. The advantages of Rh₂(R-BTPCP)₄ include its ease of synthesis, its tolerance to the size of the ester group in the styryldiazoacetates, and its compatibility with dichloromethane as solvent. Computational studies suggest that the catalyst adopts a D₂-symmetric arrangement, but when the carbenoid binds to the catalyst, two of the p-bromophenyl groups on the ligands rotate outward to make room for the carbenoid and the approach of the substrate to the carbenoid.

Full text of DOI:10.1021/ja2074104

ARTICLE
pubs.acs.org/JACS
D2-Symmetric Dirhodium Catalyst Derived from a 1,2,2-Triarylcyclo-
propanecarboxylate Ligand: Design, Synthesis and Application
Changming Qin,† Vyacheslav Boyarskikh,† Jørn H. Hansen,† Kenneth I. Hardcastle,†
Djamaladdin G. Musaev,*,‡ and Huw M. L. Davies*,†
†Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States
‡Cherry L. Emerson Center for Scientific Computation, Emory University, 1521 Dickey Drive, Atlanta, Georgia 30322, United States
S Supporting Information
b
ABSTRACT: Dirhodium tetrakis-(R)-(1-(4-bromophenyl)-
2,2-diphenylcyclopropanecarboxylate) (Rh2(R-BTPCP)4) was
found to be an effective chiral catalyst for enantioselective
reactions of aryl- and styryldiazoacetates. Highly enantioselec-
tive cyclopropanations, tandem cyclopropanation/Cope rear-
rangements and a combined CÀH functionalization/Cope
rearrangement were achieved using Rh2(R-BTPCP)4 as cata-
lyst. The advantages of Rh2(R-BTPCP)4 include its ease of
synthesis, its tolerance to the size of the ester group in the
styryldiazoacetates, and its compatibility with dichloromethane
as solvent. Computational studies suggest that the catalyst adopts a D2-symmetric arrangement, but when the carbenoid binds to the
catalyst, two of the p-bromophenyl groups on the ligands rotate outward to make room for the carbenoid and the approach of the
substrate to the carbenoid.
’ INTRODUCTION
with the possibility of using the new asymmetric transformations
to enable the design of new chiral catalysts. Indeed, the inspira-
tion for the development of Rh2(S-PTAD)4, a related catalyst to
Hashimoto’s catalyst Rh2(S-PTTL)4 (5),3e came from the dis-
covery that donor/acceptor carbenoids undergo enantioselective
CÀH functionalization of adamantane.4 Donor/acceptor carbe-
noids are also capable of generating highly substituted cyclopro-
panes with high enantioselectivity.3f,4À6,11 We decided to explore
whether the resulting cyclopropanecarboxylic acids would be
useful ligands for dirhodium catalysts. The cyclopropane ring
would be expected to limit the possible conformations of the
ligands and in this way we would hope to address the limitations
observed with the Rh2(S-DOSP)4 catalyst.3f
Dirhodium catalysts have played a prominent role in the
metal-catalyzed reactions of diazo compounds.1 Over the past
few decades, great effort has been made to prepare various chiral
dirhodium tetracarboxylate and dirhodium tetracarboxamidate
catalysts.2,3 Our group has studied a series of prolinate-based
dirhodium catalysts, such as Rh2(S-DOSP)4 (1, Figure 1),3f and
examined their capacity to induce high asymmetric induction in
the reactions of donor/acceptor carbenoids.1a The asymmetric
induction in these catalyzed reactions is sensitive to solvent and
substrate structure.3f High asymmetric induction with Rh2(S-
DOSP)4 as catalyst requires the use of a methyl ester as the
acceptor group in the carbenoid and nonpolar solvents such as
hydrocarbons.3f Although our effort to solve these limitations has
led to the development of other promising catalysts, such as the
phthalimidocarboxylate Rh2(S-PTAD)4 (2)4 and the bridged
dicarboxylate catalyst, Rh2(S-biTISP)2 (3),5 the relatively te-
dious synthetic routes to these catalysts erode their overall
appeal. Therefore, the development of both synthetically acces-
sible and highly selective chiral dirhodium catalysts remains
highly desirable. Herein, we report the concise synthesis of a
novel catalyst, Rh2(R-BTPCP)4 (4), and its application in highly
enantioselective transformations of donor/acceptor carbenoids.
Over the past few years, we have developed several novel
enantioselective reactions of donor/acceptor carbenoids, such as
cyclopropanation,3f,4À6 formal [4 + 3] cycloaddition,7 CÀH
functionalization,1a and ylide transformations.8 These reactions
have been used in total synthesis9 and as enabling technologies in
medicinal chemistry programs.7,10 We have become intrigued
’ RESULTS AND DISCUSSION
To evaluate the utility of cyclopropanecarboxylate catalysts,
the 1,2-diphenylcyclopropanecarboxylate complex 8, Rh2(R-
DPCP)4, was prepared (Scheme 1). Rh2(R-DOSP)4-catalyzed
enantioselective cyclopropanation of styrene 6 with methyl
phenyldiazoacetate 7, afforded the diarylcyclopropanecarboxy-
late in 81% yield, >20: 1 dr and 91% ee,6 which was further
enriched to >99% ee by recrystallization. A sequential hydrolysis
and recrystallization provided the diphenylcyclopropanecar-
boxylic acid in 60% yield and >99% ee. Finally, ligand exchange
with sodium rhodium carbonate in refluxing water gave 8 in
65% yield.
Received: August 27, 2011
Published: November 02, 2011
r
2011 American Chemical Society
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Scheme 3. Synthesis of Rh2(R-BTPCP)4
Table 1. Initial Evaluation of Rh2(R-BTPCP)4- and Rh2(R-
DOSP)4-Catalyzed Cyclopropanationa
Figure 1. Chiral dirhodium catalysts.
Rh2(R-BTPCP)4
Rh2(R-DOSP)4
Scheme 1. Synthesis of Rh2(R-DPCP)4
temp. time
ee
yield
(%)
ee
entry solvent (°C) (h)
yield (%)
(%)
(%)
1
2
3
4
pentane
CH2CI2
CH2CI2
23
23
0
1.5
1.5
2.0
82
86
72
71
77
46
84b
91
92c
85
80
81
78
69
38
92
81
84
87
81
81
CH2CI2 À78 12
91
5d CH2CI2
6e CH2CI2
23 24
92
23 60
92
a Standard conditions: 9 (0.4 mmol) was added to a solution of Rh(II)
catalyst and styrene (2.0 mmol) under argon over 1 h. Reported yields
were obtained after chromatographic purification. dr was determined
by 1H NMR prior to chromatography, and ee was determined by chiral
HPLC. Absolute configuration of 10 was assigned according to
Scheme 2. Evaluation of Rh2(R-DPCP)4
b
previous studies.3f À89% ee was obtained when Rh2(S-BTPCP)4
was used. c Rh2(S-BTPCP)4 was used. d 0.1 mol % catalyst. e 0.01 mol %
catalyst.
Standard ligand exchange conditions generated Rh2(R-BTPCP)4
(4) in 63% yield as a green solid.
The selectivity of Rh2(R-DPCP)4 was evaluated in the standard
cyclopropanation reaction between styrene 6 and styryldiazoacetate
9 using dichloromethane as solvent (Scheme 2). The styrylcyclo-
propane 10 was formed in 81% yield and with high diastereos-
electivity (>20: 1 dr), which is typical for the cyclopropanation
chemistry of donor/acceptor carbenoids. However, the asymmetric
induction exhibited by Rh2(R-DPCP)4 was only 11% ee.
At this stage, we re-examined what might be required for an
effective cyclopropanecarboxylate ligand. Even though the cy-
clopropanecarboxylate in 8 has two stereogenic centers, the two
phenyl rings are on the opposite side of the ring to the carboxy-
late. Therefore, the phenyl rings are not likely to display a major
chiral influence on the catalyst nor are they likely to limit con-
formational mobility of the ligands. To overcome this issue, we
decided to make a ligand with an additional phenyl ring syn- to
the carboxylate. The triarylcyclopropanecarboxylate, was prepared
from Rh2(R-DOSP)4 catalyzed cyclopropanation reactions between
1,1-diphenylethylene (11) and para-bromophenyl diazoacetate 12
(Scheme 3). As previously established, this type of cyclopropa-
nation proceeds with very high enantioselectivity.6,11 The cyclo-
propane ester was converted to the corresponding carboxylic
acid by tBuOK in dimethyl sulfoxide without erosion of enantios-
electivity and was enriched to 99% ee after recrystallization.
With Rh2(R-BTPCP)4 in hand, its efficiency was examined in
the standard reaction between the styryldiazoacetate 9 and
styrene 6. The influence of the syn-phenyl group in the ligand
was dramatic as the reaction in dichloromethane at 23 °C generated
the cyclopropane 10 in 91% ee, which is better than the same
reaction catalyzed by Rh2(R-DOSP)4 (81% ee), (Table 1, entry 2).
Further experiments comparing Rh2(R-BTPCP)4 and Rh2(R-
DOSP)4 are summarized in Table 1. Temperature did not
influence the enantioselectivity of the Rh2(R-BTPCP)4-catalyzed
reaction between 9 and styrene 6 as 10 was produced in 91% ee
over a reaction temperature range from 23 to À78 °C (Table 1,
entries 2, 4). Furthermore, decreasing the catalyst loading from
1 to 0.01 mol % did not alter the enantioselectivity (Table 1,
entries 5, 6),12 but the reaction did not go to completion at the
0.01 mol % catalyst loading.
High asymmetric induction with Rh2(S-DOSP)4 can only be
obtained when the electron-withdrawing group is a methyl
ester.3f Even changing the methyl ester to a tert-butyl ester
caused a dramatic drop in the enantioselectivity. Therefore, a
study was undertaken to determine how Rh2(R-BTPCP)4-cata-
lyzed reactions responded to the size of the ester (Table 2).
Rh2(R-BTPCP)4 exhibited good tolerance to ester size, and the
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enantioselectivity actually improved on increasing the ester size
from methyl to tert-butyl (Table 2, entries 1À4, from 91% ee
to 95% ee). In contrast, hindered esters were confirmed to have
a detrimental effect on asymmetric induction with Rh2(R-
DOSP)4, leading to a steady drop in enantioselectivity from
81% ee to 16% ee (Table 2, entries, 5À8).
All the reactions proceeded smoothly in dichloromethane, affording
the corresponding cyclopropanes 16a-k with high diastereo- and
enantioselectivity with yields ranging from 59% to 94%. Carbenoid
precursors with electron-donating substituents on the donor
group (Table 3, entry 11) resulted in higher asymmetric induction
than those having electron-withdrawing substituents on the donor
group (Table 3, entries 9, 10). Electron-deficient alkenes gave better
enantioselectivity than electron-rich alkenes. An optimum system is
para-trifluoromethylstyrene and its reaction with styryldiazoace-
tate 9, produced the cyclopropane 16a in 97% ee (Table 3, entry
1). In contrast, the reaction with para-methoxystyrene produced
the corresponding cyclopropane 16e in 83% ee at room tem-
perature, but this could be improved to 93% ee when the reaction
was conducted at À40 °C (Table 3, entry 5). Inclusion of an
ortho substituent on the styrene had little influence on the
enantioselectivity, as reaction of ortho-methylstyrene and methyl
To probe the generality of this catalyst in enantioselective
cyclopropanation with donor/acceptor carbenoid intermediates,
various combinations of aryl- or vinyldiazoacetates with terminal
alkenes were evaluated. The results for representative vinyldia-
zoacetates and terminal alkenes are summarized in Table 3.
Table 2. Effect of Ester Size on Asymmetric
Cyclopropanationa
Table 4. Rh2(R-BTPCP)4-Catalyzed Asymmetric Cyclopro-
panation with Aryldiazoacetatesa
starting
yield
(%)
ee
entry material
R
catalyst
product
(%)
1
2
3
4
5
6
7
8
9
Me
Et
i-Pr
Rh2(R-BTPCP)4
Rh2(R-BTPCP)4
Rh2(R-BTPCP)4
10
86
88
89
87
80
84
82
80
91
93
96
95
81
75
55
16
13a
13b
13c
9
14a
14b
14c
10
entry starting material
R
product yield (%) ee (%)
t‑Bu Rh2(R-BTPCP)4
1
2
3
4
7
Ph
18a
18b
18c
18d
82
80
74
86
83
85
91
89
Me
Et
i-Pr
tBu
Rh2(R-DOSP)4
Rh2(R-DOSP)4
Rh2(R-DOSP)4
Rh2(R-DOSP)4
12
p-BrC6H4
13a
13b
13c
14a
14b
14c
17a
17b
p-MeOC6H4
p-CF3C6H4
a Standard conditions: Diazo compound (0.4 mmol) was added to a
solution of Rh(II) catalyst and styrene (2.0 mmol) in dichloromethane
under argon over 1 h. Reported yields were obtained after chromatographic
purification. dr was determined by 1H NMR prior to chromatography, and
ee was determined by chiral HPLC. Absolute configuration of the products
was assigned according to previous studies.6
a Standard conditions: Diazo compound (0.4 mmol) was added to a
solution of Rh(II) catalyst and styrene (2.0 mmol) in dichloromethane
under argon over 1 h. Reported yields were obtained after chromato-
graphic purification. dr was determined by 1H NMR prior to chroma-
tography, and ee was determined by chiral HPLC.
Table 3. Rh2(R-BTPCP)4-Catalyzed Asymmetric Cyclopropanation with Styryldiazoacetatesa
entry
R1
diazo compound
R2
product
yield (%)
ee (%)
1
p-CF3C6H4
p-NO2C6H4
p-CIC6H4
3,4-diCIC6H3
p-MeOC6H4
o-CH3C6H4
o-MeO2CC6H4
H3C(CH2)3
Ph
9
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
16a
16b
16c
16d
16e
16f
87
92
86
88
94
88
59
60
82
79
70
97
95
2
9
3
9
95
4
9
93
84(93)b
5
9
6
9
93
7
9
16g
16h
16i
89
90c
8
9
9
15a
15c
15d
p-CIC6H4
90
10
11
Ph
3,4-diCIC6H3
3,4-diMeOC6H3
16j
86
À93d
Ph
16k
a Standard conditions: Diazo compound (0.4 mmol) was added to a solution of Rh(II) catalyst and styrene (2.0 mmol) in dichloromethane under argon
1
over 1 h. Reported yields were obtained after chromatographic purification. dr was determined by H NMR prior to chromatography, and ee was
determined by chiral HPLC. b Reaction was conducted at À40 °C. c dr >10:1. d Rh2(S-BTPCP)4 was used as catalyst.
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Table 5. Rh2(R-BTPCP)4 Catalyzed Tandem Cyclopropa-
nation/Cope Rearrangementa
entry
starting diene
product
yield (%)
ee (%)
R
1
2
3
19a
19b
19c
Ph
20a
20b
20c
56
71
60
87
91
89
Figure 2. Three distinct ligand orientations used to rationalize en-
antioselectivity in dirhodium carboxylate-catalyzed reactions.
p-CF3C6H4
p-MeOC6H4
a Standard conditions: Diazo compound (0.4 mmol) was added to a
solution of Rh(II) catalyst and styrene (2.0 mmol) in dichloromethane
at À40 °C under argon over 1 h. Reported yields were obtained after
chromatographic purification. dr was determined by 1H NMR prior to
chromatography, and ee was determined by chiral HPLC. Absolute
configuration of the products was assigned according to previous
studies.7a
Scheme 4. Combined CÀH Cope/Retro-Cope Reactiona
Figure 3. X-ray crystal structure of Rh2(R-BTPCP)4 (axial ligands
omitted for clarity).
Even though dirhodium tetracarboxylates contain two poten-
tially reactive rhodium sites and four identical ligands of C1
symmetry, they are capable of very high asymmetric induction.2a
Previously, this feature was explained by envisioning the dirho-
dium tetracarboxylates in conformations of higher symmetry
than the ligands themselves. For Rh2(S-DOSP)4-catalyzed reac-
tions, we proposed the catalyst to preferentially exist in a D2
symmetric “up-down-up-down” conformation, providing identi-
cal C2 symmetric binding sites at both rhodium faces of the
catalyst (Figure 2).3f Hashimoto rationalized the selectivity of his
phthalimido amino acid derived catalysts by proposing a C2
symmetric “up-up-down-down” arrangement for the catalyst.3e
More recently, Fox reported that the tert-butyl catalyst Rh2(S-
PTTL)4, the most broadly used of Hashimoto’s catalysts, exists in
an “all-up” distorted C4 conformation.3h,i According to this
model, the bulky tert-butyl groups are necessary to limit reactivity
to only one of the Rh faces of the catalyst, whereas a distorted C4
symmetric chiral crown-like ligand arrangement guides the facial
selectivity at the open Rh-face. Recently, other groups have
reported X-ray structures of related catalysts to Rh2(S-PTTL)4,
and all these catalysts adopt an “all-up” C4 conformation.3j,k,m,n
Because Rh2(R-BTPCP)4 is structurally quite different from the
other above-mentioned chiral dirhodium tetracarboxylate cata-
lysts, a study to determine what made it such an effective chiral
catalyst was undertaken.
2-vinylbenzoate with the styryldiazoacetate 9 provided the
cyclopropanes 16f and 16g in 93% ee and 89% ee, respectively
(Table 3, entries 6, 7). Unactivated alkenes are also suitable
substrates as 1-hexene (Table 3, entry 8) gave the cyclopropane
16h in 60% yield and 90% ee.
The cyclopropanation reactions of representative aryldiazoa-
cetates are summarized in Table 4. The reactions generated the
cyclopropanes 18aÀd in high yield and stereoselectivity (>20:1
dr, 83À91% ee), with p-methoxyphenyl derivative 17a giving the
highest enantioselectivity (91% ee). These results are similar to
the reported results for the Rh2(S-DOSP)4-catalyzed cyclopro-
panations of aryldiazoacetates in hexane as solvent.6
Encouraged by the cyclopropanation results, we decided to
investigate the scope of the catalyst further by looking at more
elaborate reactions of vinyldiazoacetates. When vinyldiazoace-
tates react with dienes, a formal [4 + 3] cycloaddition occurs by a
tandem cyclopropanation/Cope rearrangement.7 The Rh2(R-
BTPCP)4-catalyzed reactions of styryldiazoacetate 9 with dienes
19 gave rise to the cycloheptadienes 20 in 56À71% yield and the
enantioselectivity was 87À91% ee. As is typical of this transformation,7
20 were formed as single diastereomers.
In recent years, vinyldiazoacetates have been shown to be
broadly useful in a range of CÀH functionalization reactions.1a
An example is the formal CÀH functionalization of dihydro-
naphthalene 21 to form 22.13 This reaction proceeds by a
sequence involving a combined CÀH functionalization/Cope
rearrangement followed by a reverse Cope rearrangement. When
this reaction was catalyzed by Rh2(R-BTPCP)4, the product 22
was formed in 92% yield as a single diastereomer and in 98% ee
(Scheme 4).13 This result compares favorably to the Rh2(S-
DOSP)4-catalyzed formation of 22 with hexane as solvent.
A single crystal X-ray diffraction analysis of Rh2(R-BTPCP)4
provided valuable insights into the catalyst geometry. In the
X-ray structure, the large chiral ligands of Rh2(R-BTPCP)4 are
organized in an overall D2 symmetric arrangement, forming
identical rectangular orthogonal (approximately 8.5 Â 10.5 Å)
binding cavities of C2 symmetry at the two catalytically active
axial termini of the rhodium dimer (Figure 3).
Rh2(R-BTPCP)4 and Rh2(S-PTTL)4 have different overall
symmetry, D2 and distorted C4, respectively, but they possess a
related rectangular binding cavity at the reactive axial positions
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Figure 6. ONIOM partitioning of Rh2(R-BTPCP)4-carbene complex.
Figure 4. Catalytically active sites of Rh2(R-BTPCP)4 (X-ray) and
Rh2(S-PTTL)4 (calculated structure).
Figure 7. Lowest-energy conformation of s-trans carbene, top view
(left) and side view (right). Hydrogen atoms were omitted for clarity.
s-trans carbenoid conformation would not fit into the tight
environment (the dimensions shown on Figures 4 and 5 were
measured from atomic centers and do not account for atomic
radii) of the Rh2(R-BTPCP)4 catalyst.
Performing DFT calculations on the complete rhodium
carbene complex (approximately 200 atoms) would be imprac-
tical unless very small basis sets were used,3i and these may not
give a realistic representation of the complex. Therefore, we
employ an alternative ONIOM approach18 to study the carbe-
noid reaction. A two-layer ONIOM (QM:MM) method used in
these studies divides the whole system into two subsystems
(denoted “model” and “real” layers) and treat them at the best
possible level of theory. The ONIOM partitioning of the catalyst-
carbene system that was used is shown in Figure 6. In these
studies the B3LYP15À17 and UFF19 methods were used for the
calculations of the “model” (in red) and “real” (in blue) layers,
respectively. Such partition provided an accurate description for
the central rhodium carboxylate-carbene complex and accounted
for the steric influence of the surrounding ligands.
Our computational results support the importance of the
steric environment within the catalyst. Thus even the best
matching combination of the shortest s-trans carbene aligned
with the widest dimension of the orthogonal binding cavity
caused steric repulsions significant enough to rotate two para-
bromophenyl groups in either conrotary or disrotary directions.
A similar result was obtained when the s-trans carbene was
aligned with the shortest catalyst dimension; this time the phenyl
groups rotated in a similar way. Overall, we were able to locate
sixteen distinct minima on the potential energy surface corre-
sponding to different conformations of the s-trans carbene with
Rh2(R-BTPCP)4. The lowest energy conformation, separated
from the closest one by ΔE = 1.8 kcal/mol is depicted in Figure 7.
In this conformer two ligands rotated in a conrotary fashion to
minimize steric interactions with the carbene, whereas the other
two ligands remained in the upward position to reduce steric
Figure 5. DFT model of s-cis and s-trans carbene conformers.
(Figure 4). The rectangular biding cavity for Rh2(R-BTPCP)4
(8.5 Â 10.5 Å) is significantly smaller than the cavity for Rh2(S-
PTTL)4 (12.8 Â 14.1 Å). Furthermore, both Rh faces of Rh2(R-
BTPCP)4 have identical binding cavities of C2 symmetry. How-
ever, for Rh2(S-PTTL)4 only one Rh face has the rectangular
binding cavity, whereas the other face is considered to be blocked
by the tert-butyl groups. According to the Rh2(S-PTTL)4 model
proposed by Fox,3h,i a carbene would align with the wide dimen-
sion of the catalyst leaving the Si face open for the attack because
of the wider gap between two of the ligands. To test if the same
model could be utilized to explain the stereochemical outcome
of Rh2(R-BTPCP)4-catalyzed transformations, a computational
analysis of the catalyst-carbene complex was conducted.
Traditional computational approaches to analyze dirhodium
carbene complexes have tended to rely on the X-ray structure of
the catalyst in combination with DFT optimized geometries of
the carbenoid with a simplified, achiral, catalyst model.3j,m,14
Although such analysis may provide preliminary insights into the
catalyst selectivity, more precise studies accounting for interac-
tions between the carbene and ligands, as well as ligand mobility
in these systems would give a much better understanding of
the role of the chiral catalyst. In fact, our preliminary DFT
calculations15À17 on the simplified model of the dirhodium-
(tetracarboxylate)-carbene complex (Figure 5) demonstrates the
importance of such studies. A comparison of the DFT optimized
geometries, given in Figure 5, with the reported size of the
catalyst binding cavity (Figure 4) reveals that even the shortest
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CHE-0553581 and the use of computational resources at the
Cherry Emerson Center for Scientific Computation
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Figure 8. Predictive stereochemical model for Rh2(R-BTPCP)4-cata-
lyzed transformation.
repulsions with the neighboring ligands. This arrangement
resulted in a C2 symmetric environment at the carbene site
cavity containing two phenyl rings and two para-bromophenyl
groups. One of the rings is blocking the donor group (aryl, styryl)
while the other one is positioned next to the acceptor group
(ester). The same ligand conformation having the s-cis carbene
geometry was found to be 2.5 kcal/mol higher.
On the basis of the computational data summarized above, we
propose a stereochemical model that explains the selectivity
observed in Rh2(R-BTPCP)4 catalyzed transformations (Figure 8).
It is well established that the substrate approaches donor/acceptor-
substituted rhodium-carbenoids over the donor group.17a The
ester group aligns perpendicular to the carbene plane, and blocks
attack on its side. When the substrate approaches over the donor
group, the Re-face is blocked by the aryl ring of the ligand leaving
the Si-face open for the attack. This model predicts correctly the
observed absolute configuration of the products.
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’ CONCLUSION
In conclusion, we have developed dirhodium tetrakis-triaryl-
cyclopropanecarboxylates as a new class of chiral catalysts with a
relatively rigid and easily tunable backbone. The efficiency and
selectivity of this catalyst has been demonstrated in a variety of
highly diastereo- and enantioselective reactions of donor/accep-
tor carbenoids. The computational analysis allowed us to pro-
pose a stereochemical model to explain selectivity of the new
catalyst. This analysis illustrates the importance of considering
the conformational mobility of the ligands once the carbene is
bound to the catalyst.
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’ ASSOCIATED CONTENT
S
Supporting Information. Synthetic details, computational
b
details, X-ray crystallographic data, and spectral data. This material is
available free of charge via the Internet at http://pubs.acs.org.
(13) Davies, H. M. L.; Jin, Q. H. J. Am. Chem. Soc. 2004, 126,
10862–10863.
(14) For more examples of computational analysis of dirhodium
carboxylates see: (a) Snyder, J. P.; Padwa, A.; Stengel, T. J. Am. Chem.
Soc. 2001, 123, 11318–11319. (b) Nakamura, E.; Yoshikai, N.; Yama-
naka, M. J. Am. Chem. Soc. 2002, 124, 7181–7192. (c) Nowlan, D. T., III;
Gregg, T. M.; Davies, H. M. L.; Singleton, D. A. J. Am. Chem. Soc. 2003,
125, 15902–15911. (d) Nowlan, D. T., III; Singleton, D. A. J. Am. Chem.
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B. T.; Pelphrey, P.; Jin, Q.; Autschbach, J.; Davies, H. M. L. Angew.
Chem., Int. Ed. 2011, 50, 2544–2548. (h) Hansen, J.; Gregg, T. M.;
Ovalles, S. R.; Lian, Y.; Autschbach, J.; Davies, H. M. L. J. Am. Chem. Soc.
2011, 133, 5076–5085. (i) Liang, Y.; Zhou, H; Yu, Z. ÀX. J. Am. Chem.
Soc. 2009, 131, 17783.
’ AUTHOR INFORMATION
Corresponding Author
hmdavie@emory.edu; dmusaev@emory.edu
’ ACKNOWLEDGMENT
We thank Dr. Janelle Thompson for preliminary studies on the
diphenylcyclopropanecarboxylate catalyst. This research was
supported by the National Science Foundation for HMLD
(CHE-07502730) and for HMLD and DGM under the Center
for Chemical Innovation in Stereoselective CÀH Functionaliza-
tion (CHE-0943980). We acknowledge the NSF-MRI grant
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Journal of the American Chemical Society
ARTICLE
(15) Calculations were performed using Gaussian ’09 software
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(16) Hybrid Density Functional method B3LYP was used through-
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with an added polarization 4f-function (ζf (Rh) = 1.350), the split
valence 6-31G(d) basis sets were used on all other atoms. See: (a)
Hansen, J.; Autschbach, J.; Davies, H. M. L. J. Org. Chem. 2009,
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(18) A combination of B3LYP and UFF methods were used in the
two-layer ONIOM (QM:MM) calculations. See Supporting Informa-
tion for the optimized geometries. For more information on the
ONIOM methodology see: (a) Dapprich, S.; Komꢀaromi, I.; Byun,
K. S.; Morokuma, K.; Frisch, M. J. THEOCHEM 1999, 461À462, 1–21.
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