Role of sterically demanding chiral dirhodium catalysts in site-selective C-H functionalization of activated primary C-H bonds

Article abstract of DOI:10.1021/ja504797x

The influence of sterically demanding dirhodium tetracarboxylate catalysts on the site selectivity of C-H functionalization by means of rhodium carbene-induced C-H insertion is described. The established dirhodium tetraprolinate-catalyzed reactions of aryldiazoacetates cause preferential C-H functionalization of secondary C-H bonds as a result of competing steric and electronic effects. The sterically more demanding dirhodium tetrakis(triarylcyclopropanecarboxylate) catalysts, exemplified by dirhodium tetrakis[(R)-(1-(biphenyl)-2,2-diphenylcyclopropanecarboxylate)] [Rh ₂(R-BPCP)₄], favor C-H functionalization of activated primary C-H bonds. Highly site-selective and enantioselective C-H functionalization of a variety of simple substrates containing primary benzylic, allylic, and methoxy C-H bonds was achieved with this catalyst. The utility of this approach has been demonstrated by the late-stage primary C-H functionalization of (-)-∝-cedrene and a steroid.

Full text of DOI:10.1021/ja504797x

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Article
Role of Sterically Demanding Chiral Dirhodium Catalysts on Site
Selective C–H Functionalization of Activated Primary C–H Bonds
Changming Qin, and Huw M. L. Davies
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 16 Jun 2014
Downloaded from http://pubs.acs.org on June 19, 2014
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Role of Sterically Demanding Chiral Dirhodium Catalysts on Site Se-
lective C–H Functionalization of Activated Primary C–H Bonds
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Changming Qin and Huw M. L. Davies*
Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322
ABSTRACT: The influence of sterically demanding dirhodium tetracarboxylate catalysts on the site selectivity of C–H functional-
ization by means of rhodium carbene induced C–H insertion is described. The established dirhodium tetraprolinate-catalyzed reac-
tions of aryldiazoacetates cause preferential C–H functionalization of secondary C–H bonds due to competing steric and electronic
effects. The sterically more demanding dirhodium tetrakis(triarylcyclopropane-carboxylate) catalysts, exemplified by dirhodium
tetrakis-[(R)-(1-(biphenyl)-2,2 diphenylcyclopropane carboxylate)] (Rh2(R-BPCP)4), favor C–H functionalization of activated pri-
mary C–H bonds. Highly site selective and enantioselective C–H functionalization of a variety of simple substrates containing
primary benzylic, allylic and methoxy C–H bonds was achieved with this catalyst. The utility of this approach has been demonstrat-
ed
in
the
late-stage
primary
C–H
functionalization
of
(-)-α-cedrene
and
a
steroid.
occur at primary C–H bonds (Scheme 1). Furthermore, these
reactions proceed with high levels of asymmetric induction.
INTRODUCTION
C–H functionalization is a research area of intense interest
because it has the potential to revolutionize the way complex
molecules are synthesized.1 One of the main challenges in this
area of chemistry is the development of predictable site selec-
tive C–H functionalization methods.2 The most successful
approaches to achieve predictable selectivity has been through
the use of directing groups.3 Even though some of these direct-
ing groups are useful for further transformations, such a strat-
egy often limits flexibility and requires additional steps to
introduce and remove the directing groups. Consequently,
many recent studies have focused on developing new ap-
proaches for site selective C–H functionalization relying on
other controlling factors.4 Particularly attractive are C–H func-
tionalization methods in which the site selectivity is under
reagent or catalyst control and can be modified as needed.
Scheme 1. Site Selectivity of Rhodium Carbene Induced
C–H Functionalization
H
N2
Rh(II)
Rh(II)
H
Ar
CO2Me
Ar
CO2Me
Ar
CO2Me
H
H
R
R
H
Rh2(R-BPCP)4
H
Rh2(R-DOSP)4
H
R
Current work
Previous work
O
O
Rh
Rh
H
H
Rh
Rh
O
O
O
N
N
In the past decades, we have been exploring the scope of
site selective intermolecular C–H functionalization by means
of rhodium-catalyzed reactions of donor/acceptor carbenes
(Scheme 1).5 The rhodium-bound donor/acceptor carbenes
have attenuated reactivity compared to acceptor only substi-
tuted carbenes,6 enabling highly selective C–H functionaliza-
tion to be achieved. The site selectivity is controlled by a deli-
cate balance of steric and electronic effects.7 Highly substitut-
ed sites are electronically favored because build-up of positive
charge occurs at the carbon during the C–H insertion step, but
this is counterbalanced by the steric demands of the carbene
complex. Thus, in the reactions with the dirhodium tetrap-
rolinate catalyst Rh2(R-DOSP)4 (Figure 1), C–H functionaliza-
tion is generally preferred at secondary C–H bonds (Scheme
1), although a few examples of functionalization of sterically
accessible tertiary C–H bonds6c,,8 and electronically activated
primary C–H bonds9 are known. In this paper, we describe a
major change in the site selectivity of carbene-induced C–H
functionalization using the bulky catalyst Rh2(R-BPCP)4 (Fig-
ure 1), which results in a strong preference for reactions to
4
ArO2S
O
Ar = 4-(C12H25)C6H4
Rh2(R-DOSP)4
4
Rh2(S-PTAD)4
Ph
Ph
Ph
Ph
Ph
O
O
Rh
Rh
Ph
O
O
Rh
Rh
Ph
O
O
Rh
Rh
4-PhC6H4
4-BrC6H4
4
4
4
Rh2(R-TPCP)4
Rh2(R-BTPCP)4
Rh2(R-BPCP)4
Figure 1. Structure of Chiral Dirhodium Catalysts
RESULTS AND DISCUSSIONS
A variety of chiral dirhodium catalysts have been prepared
to control the chemistry of donor/acceptor carbenes, and rep-
resentative catalysts are shown in Figure 1.10 We have recently
shown that catalysts with triarylcyclopropanecarboxylate lig-
ands have unusual properties because they are sterically de-
manding.10d-f We hypothesized that these bulkier catalysts
could influence the site selectivity of the C–H functionaliza-
tion of donor/acceptor carbenes. The reaction of methyl (4-
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tion8b (9:10 = 1:4). However, when Rh2(R-BPCP)4 was used, the
primary C–H functionalization product 9 was selectively formed
(9:10 > 20:1) in 75% isolated yield and 97% ee.
bromophenyl)diazoacetate 1 with 4-isopentyltoluene 2 was
used for the initial evaluation because 2 contains several types
of C–H bonds. When the established catalysts, Rh2(R-
1
2
10a
10c
3
4
5
6
7
8
9
DOSP)4 and Rh2(S-PTAD)4 were used, the reaction re-
sulted in a mixture of benzylic C–H functionalization products
3 and 411. In contrast, the triphenylcyclopropane carboxylate
catalyst Rh2(R-TPCP)4 switched the selectivity towards prima-
ry benzylic C–H bonds, providing 3 in 86% yield and 76% ee
(Table 1, entry 3). Further examination of related catalysts
revealed that the biphenyl derivative Rh2(R-BPCP)4 gave the
highest level of enantioselectivity, generating 3 in 94% ee
(entry 5). Additional optimization of solvents revealed that
Rh2(R-BPCP)4 retained high enantioselectivity when tri-
fluorotoluene and dichloromethane were used as solvent (en-
tries 6 and 7), which is different from the general behavior of
Rh2(R-DOSP)4 and Rh2(S-PTAD)4.10a,c Furthermore, good
yields of 3 could be obtained with just 1.2 equiv. of 2 and 0.5
mol% of Rh2(R-BPCP)4. Indeed, the enantioselectivity was
still unchanged when only 0.1 mol% of Rh2(R-BPCP)4 was
used but under these conditions, the yield of 3 was lower (en-
try 11). It is noted that the use of dichloromethane rather than
the expensive 2,3-dimethylbutane and only 1.2 equiv. of the
substrate adds a practical value for this reaction.
Scheme 2. C–H Functionalization of Ethyltoluene and Iso-
propyltoluenea
(p-Br)Ph
CO2Me
0.5 mol %
Rh2(L)4
(p-Br)Ph
MeO2C
N2
+
+
DCM, reflux
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
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42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
CO2Me
(p-Br)Ph
1
5
6
7
catalyst
ratio 6:7
yield (%)
ee (%) 7
Rh2(R-DOSP)4
Rh2(R-BPCP)4
<1:20
5:1
-
75
74b
92
(p-Br)Ph
CO2Me
0.5 mol %
Rh2(L)4
(p-Br)Ph
MeO2C
N2
+
+
DCM, reflux
CO2Me
(p-Br)Ph
1
8
9
10c
Table 1. Initial Studies on Selective C–H Functionalizatio-
na
catalyst
ratio 9:10
yield (%)
ee (%) 9
Rh2(R-DOSP)4
Rh2(R-BPCP)4
1:4
72a
75
73
97
>20:1
(p-Br)Ph
CO2Me
1.0 mol %
Rh2(L)4
(p-Br)Ph
MeO2C
aReaction conditions, aryldiazoacetate 1 (0.4 mmol) in di-
chloromethane (2.5 mL) was slowly added to toluene substrate
(0.48 mmol, 1.2 equiv.) and Rh2(R-BPCP)4 (3.5 mg, 0.5
mol%) in reflux dichloromethane (1.5 mL) in 1.5 h, then re-
N2
+
+
Sol, Temp.
CO2Me
(p-Br)Ph
c
flux 1.5 h in an argon atmosphere. bCombined yield. 10, 55%
1
2
3
4
ee under Rh2(R-DOSP)4 catalyst.
yield (%)b
ee (%) 3
catalyst
solvent (eq.) 2
entry
ratio 3:4
1
2
3
70
73
86
90
90
84
87
84
84
82
63
77
70
76
90
94
89
94
95
95
95
95
Rh2(R-DOSP)4
Rh2(S-PTAD)4
Rh2(R-TPCP)4
Rh2(R-BTPCP)4
Rh2(R-BPCP)4
Rh2(R-BPCP)4
Rh2(R-BPCP)4
Rh2(R-BPCP)4
Rh2(R-BPCP)4
Rh2(R-BPCP)4
Rh2(R-BPCP)4
1:1.7
1.1:1
DMB
DMB
DMB
DMB
DMB
PhCF3
DCM
DCM
DCM
DCM
DCM
5.0
5.0
5.0
5.0
5.0
5.0
5.0
2.0
1.2
1.2
1.2
The scope of the Rh2(R-BPCP)4-catalyzed C–H functionali-
zation by methyl aryldiazoacetates 1 and 11 was then exam-
ined with a range of aromatic substrates (Table 2). Good site
selectivity and enantioselectivity was achieved with a variety
of aryldiazoacetates 11a-c as illustrated for 13a-c (>20:1 1°,
90-92% ee). Even though the Rh2(R-BPCP)4-catalyzed reac-
tion of 1 with ethyltoluene gave a mixture of primary and sec-
ondary C–H insertion products, when the secondary site was
slightly larger such as iso-butyl, n-butyl, and even n-propyl,
the reaction was highly site selective as illustrated for 13d-f
(>20:1 1°, 95-96% ee). It was expected that the site selectivity
would be more challenging in the systems containing compet-
ing methoxy and iso-butoxy groups, but once again 13g and
13h were cleanly formed (>20:1 1°, 90-91% ee). The reaction
was compatible with alkyne and ester functional groups as
illustrated for 13i-k (>20:1 1°, 94-95% ee), but the yield of the
ester derivative 12k was only 38%, presumably because the
primary methyl group is not as activated on account of the
electron withdrawing nature of the ester group. The absolute
configuration of product 3 was determined by X-ray crystal-
lography of a related derivative (see supporting information
for details). The absolute configuration of 3 is in agreement
with the predicted model developed for the face selectivity of
dirhodium tetrakis(triarylphenylcyclopropane carboxylate)-
catalyzed carbene reactions.10d The absolute configuration of
the other products was assigned by analogy.
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
4
5
6c
7
8
9
10d
11e
aStandard reaction conditions, aryldiazoacetate 1 (0.4 mmol)
was added to 2 and catalyst (1 mol%) in the indicated reflux
solvent in 1.5 h, in an argon atmosphere, and then reflux an-
other 1.5 h after addition. bIsolated yield of 3, yields in entry 1
c
and 2 refer to the combined yield of 3 and 4. 55 °C internal
d
e
temperature. 0.5 mol% catalyst loading. 0.1 mol% catalyst
loading.
We subsequently explored the influence of Rh2(R-BPCP)4 with
more challenging substrates (Scheme 2) The Rh2(R-DOSP)4-
catalyzed reaction of 4-ethyltoluene (5) is known to occur selec-
tively at the secondary benzylic site (6:7 < 1:20).9a In contrast, the
Rh2(R-BPCP)4-catalyzed reaction favors C–H functionalization at
the primary C–H bond (6:7 = 5:1) in a 74% combined isolated
yield, with 6 produced in 92% ee. Another challenging substrate
is isopropyl toluene (8), which under Rh2(R-DOSP)4-catalyzed
reaction gave a mixture of primary/tertiary C-H functionaliza-
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Having established that Rh2(R-BPCP)4 enhances C–H func-
In certain cases, Rh2(R-DOSP)4-catalyzed reactions can lead
to a mixture of C–H functionalization and cyclopropanation
products.7a,b Therefore, it became of interest to determine
whether Rh2(R-BPCP)4 would influence the chemoselectivity
of such system. One example that leads to a mixture is the
Rh2(R-DOSP)4-catalyzed reaction of 1 with trans-anethole,
which generated a 5:1 mixture of the C-H insertion 21 and
cyclopropanation 22 products (Scheme 4). A previous report
1
2
3
4
5
6
7
8
tionalization of primary benzylic C–H bonds, studies were
then conducted to determine if the same trend would be seen
for allylic C–H functionalization (Scheme 3). Rh2(R-DOSP)4-
catalyzed reaction of aryldiazoacetate 1 and (E)-4-methylpent-
2-ene 14 produced a mixture of C–H functionalization prod-
ucts, favoring the tertiary C–H insertion product 16 in poor
enantioselectivity (48% ee); however, Rh2(R-BPCP)4 switched
the selectivity towards the primary C-H bond and strongly
favored the formation of 15 (15:16 = 17:1, 94% ee, Scheme 3).
9
Scheme 3. C–H Functionalization of (E)-4-Methylpent-2-
ene and (E)-2-Hexenea
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 2. Selective C–H Functionalization of Toluene De-
rivativesa
Ph(p-Br)
0.5 mol %
Rh2(R-BPCP)4
(p-Br)Ph
MeO2C
CO2Me
+
N2
+
R
R
CO2Me
DCM, reflux
0.5 mol %
Rh2(R-BPCP)4
Ar
(p-Br)Ph
+
N2
MeO2C
14
16
ee (%) 15
1
DCM, reflux
15
CO2Me
Ar
catalyst
ratio 15:16
yield (%)
Rh2(R-DOSP)4
Rh2(R-BPCP)4
1:7
81b
60
-
1, 11a-c
2, 12a-h
13a-k
17:1
94
(p-Br)Ph
(p-Br)Ph
MeO2C
0.5 mol %
Rh2(R-BPCP)4
CO2Me
+
N2
+
CO2Me
CO2Me
CO2Me
DCM, reflux
CO2Me
Ph
(p-Br)Ph
(p-F)Ph
(p-TfO)Ph
1
17
18
19
13c, 73%, 90% ee
13a, 62%, 92% ee
13b, 70%, 90% ee
catalyst
ratio 18:19
yield (%)b
ee (%) 18
-
Rh2(R-DOSP)4
Rh2(R-BPCP)4
1:9
8:1
75
80
95
aReaction conditions, aryldiazoacetate 1 (0.4 mmol) in di-
chloromethane (2.5 mL) was slowly added to 14 or 17 (0.48
mmol, 1.2 equiv.) and Rh2(R-BPCP)4 (3.5 mg, 0.5 mol %) in
reflux dichloromethane (1.5 mL) in 1.5 h, then reflux 1.5 h in
CO2Me
(p-Br)Ph
CO2Me
CO2Me
(p-Br)Ph
(p-Br)Ph
13f, 83%, 96% ee
13d, 88%, 95% ee
13e, 86%, 96% ee
b
an argon atmosphere. Combined yield.
O
O
Scheme 4. C–H Functionalization of Trans-Anetholea
O
O
O
CO2Me
CO2Me
0.5 mol %
Rh2(L)4
(p-Br)Ph
MeO2C
(p-Br)Ph
13h, 85%, 90% ee
(p-Br)Ph
+
N2
+
DCM, reflux
CO2Me
13g, 85%, 91% ee
Ph(p-Br)
CO2Me
O
O
O
O
(p-Br)Ph
1
20
21
22
catalyst
ratio 21:22
ee (%) 21
yield (%)
CO2Me
CO2Me
CO2Me
76
88
Rh2(R-DOSP)4
Rh2(R-BPCP)4
5:1
76b
85
(p-Br)Ph
16:1
(p-Br)Ph
13i, 58%, 95% ee
(p-Br)Ph
13j, 66%, 94% ee
aReaction conditions, aryldiazoacetate 1 (0.4 mmol) in di-
chloromethane (2.5 mL) was slowly added to 20 (0.48 mmol,
1.2 equiv.) and Rh2(R-BPCP)4 (3.5 mg, 0.5 mol %) in reflux
dichloromethane (1.5 mL) in 1.5 h, then reflux 1.5 h in an
13k, 38%, 94% ee
aReaction conditions, aryldiazoacetate (0.4 mmol) in di-
chloromethane (2.5 mL) was slowly added to toluene substrate
(0.48 mmol, 1.2 equiv.) and Rh2(R-BPCP)4 (3.5 mg, 0.5 mol
%) in reflux dichloromethane (1.5 mL) in 1.5 h, then reflux
1.5 h in an argon atmosphere; >20:1 1o achieved in all cases.
b
argon atmosphere. Combined yield.
indicated that the use of a sterically congested dirhodium cata-
lyst Rh2(TPA)4 could improve the selectivity toward primary
C–H insertion (21:22 >15:1) in 2,3-dimethylbutane.7a When
the reaction was conducted using Rh2(R-BPCP)4 as catalyst,
the chemoselectivity has the same trend, providing the primary
C–H insertion product in 85% isolated yield and 88% ee
(21:22 = 16:1).
The same trend of selectivity was also seen with 2-hexene 17.
Rh2(R-BPCP)4-catalyzed reaction prefers to give product 18 in
high enantioselectivity (95% ee) while Rh2(R-DOSP)4-
catalyzed transformation favors the vinyl methylene site,
providing a mixture of diasteromers 19.
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Enhanced site selectivity was also observed with unsym- omers were formed, whereas the Rh2(S-DOSP)4-catalyzed
1
2
3
4
5
6
7
8
metrical ethers (Scheme 5). The Rh2(R-DOSP)4-catalyzed
reaction of 1 with methyl butyl ether gave a mixture of 24 and
25. In contrast, the Rh2(R-BPCP)4-catalyzed reaction dramati-
cally improved the selectivity for the primary C–H bond
(>20:1), affording the product 24 in high yield (86%), but with
relatively moderate enantioselectivity (64% ee).
reaction appears to be the matched reaction because 29 is
formed in a 16:1 mixture, favoring the opposite diastereomer.
The chiral influence is more pronounced with the Rh2(BPCP)4
catalysts. The Rh2(R-BPCP)4-catalyzed reaction gave a 6:1
mixture of diastereomers, while Rh2(S-BPCP)4-catalyzed reac-
tion gave a > 20:1 of the opposite diastereomer, which can be
isolated in 96% yield. The absolute configuration of the new
stereogenic center generated in the matched reactions was
tentatively assigned as (R) by analogy.
Scheme 5. C–H Functionalization of 1-Methoxybutanea
9
Ph(p-Br)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
0.5 mol %
Rh2(L)4
(p-Br)Ph
MeO2C
Scheme 7. Late-Stage C–H Functionalization of Steroida
CO2Me
N2
CO2Me
+
+
O
O
DCM, reflux.
O
Ph(p-Br)
1
(p-Br)Ph
1
23
24
25
N2
H
H
MeO2C
H
catalyst
ratio 24:25
yield (%)
ee (%) 24
H
0.5 mol %
Rh2L4
DCM, reflux
H
H
H
H
Rh2(R-DOSP)4
Rh2(R-BPCP)4
3:2
77b
86
61
64
>20:1
CO2Me
29
(p-Br)Ph
aReaction conditions, aryldiazoacetate 1 (0.4 mmol) in di-
chloromethane (2.5 mL) was slowly added to 23 (0.48 mmol,
1.2 equiv.) and Rh2(R-BPCP)4 (3.5 mg, 0.5 mol %) in reflux
dichloromethane (1.5 mL) in 1.5 h, then reflux 1.5 h in an
28
catalyst
yield (%)b
dr
Rh2(R-DOSP)4
Rh2(S-DOSP)4
Rh2(R-BPCP)4
Rh2(S-BPCP)4
82
86
89
96
1:3
b
16:1
1:6
argon atmosphere. Combined yield.
>20:1
aReaction conditions, aryldiazoacetate 1 (0.4 mmol) in di-
chloromethane (2.5 mL) was slowly added to 28 (0.48 mmol,
1.2 equiv.) and Rh2(R-BPCP)4 (3.5 mg, 0.5 mol %) in reflux
dichloromethane (1.5 mL) in 1.5 h, then reflux 1.5 h in an
argon atmosphere. Combined yield of the two diasteromers
for the top three entries.
To challenge the high selectivity of Rh2(BPCP)4, (-)-α-
cedrene 26 was considered to be an interesting substrate be-
cause it contains primary, secondary and tertiary allylic C–H
bonds (Scheme 6). The Rh2(S-BPCP)4-catalyzed reaction of 1
with 26 proceeded cleanly and afforded the primary allylic C–
H functionalization product 27 in 88% yield as a single dia-
stereomer. No other regioisomers were observed in the 1H
NMR of the crude reaction mixture. The absolute configura-
tion of 27 was determined by X-ray crystallography (see sup-
porting information for details). The asymmetric induction
observed in the formation of the new stereogenic center in 27
is consistent with what had been seen in 13l, supporting the
tentative assignments of the absolute configurations of the
other products by analogy.
b
CONCLUSION
We have developed an effective method for highly selective
C–H functionalization of primary C–H bonds. The method
was successfully applied to selective C–H functionalization of
complex targets such as (-)-α-cedrene and a steroid. This study
illustrates that highly site selective C–H functionalization can
be achieved without resorting to directing groups. Moreover,
the catalyst can be a major controlling element of the site se-
lectivity. Further application this family of dirhodium catalyst
in asymmetric transformation is underway.
Scheme 6. Selective C–H Functionalization of (-)-α-
Cedrenea
0.5 mol %
Rh2(S-BPCP)4
(p-Br)Ph
+
N2
H
ASSOCIATED CONTENT
MeO2C
DCM, reflux
88%
H
CO2Me
27
Supporting Information
(p-Br)Ph
1
26
Full experimental data for the compounds described in the paper
and X-ray crystallographic data (CIF). This material is available
free of charge via the Internet at http://pubs.acs.org.
aReaction conditions, aryldiazoacetate 1 (0.4 mmol) in di-
chloromethane (2.5 mL) was slowly added to 26 (0.48 mmol,
1.2 equiv.) and Rh2(R-BPCP)4 (3.5 mg, 0.5 mol %) in reflux
dichloromethane (1.5 mL) in 1.5 h, then reflux 1.5 h in an
argon atmosphere.
ASSOCIATED CONTENT
Corresponding Author
hmdavie@emory.edu
A study was also conducted on the steroid derivative 28
(Scheme 7). Even though 28 has three allylic sites, the two
secondary allylic sites contained within the steroid framework
are sterically inaccessible for both the Rh2(DOSP)4 and
Rh2(BPCP)4 catalysts. However, the primary C–H functionali-
zation is still influenced by the nature of the catalyst. In the
Rh2(R-DOSP)4-catalyzed reactions, a 3:1 mixture of diastere-
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
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R. A. Acc. Chem. Res. 2012, 45, 814. (g) Pan, S. C. Beilstein J. Org.
This work was supported by NSF under the CCI Center for Selec-
Chem. 2012, 8, 1374. (h) Brustad, E. M. Nature Chem. Biology 2014,
10, 170. (i) Gorminsky, P. E.; White, M. C. J. Am. Chem. Soc. 2013,
135, 14052.
1
2
3
4
5
6
7
8
tive C-H Functionalization, CHE-1205646. We thank Dr. John
Bacsa at Emory University for the X-ray crystallographic struc-
tural determination.
(5) (a) Davies, H. M. L.; Morton, D. Chem. Soc. Rev. 2011, 40, 1857.
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(11) The stereocenter of 4 and other secondary and tertiary C–H inser-
tion products are tentatively assigned by analogy with the stereoin-
duction observed in the primary C–H insertion.
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Insert Table of Contents artwork here
1
2
3
4
H
N2
Rh(II)
CO2Me
Rh(II)
H
Ar
CO2Me
Ar
Ar
CO2Me
5
6
7
8
O
O
Rh
Rh
H
Ph
Ph
O
O
Rh
Rh
N
R
H
H
H
4
H
ArO2S
R
H
4-PhC6H4
R
4
Ar = 4-(C12H25)C6H4
9
Previous work
Rh2(R-BPCP)4
Current work
Rh2(R-DOSP)4
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