Rhodium(III)-Catalyzed Direct Coupling of Arylphosphine Derivatives with Heterobicyclic Alkenes: A Concise Route to Biarylphosphines and Dibenzophosphole Derivatives

Article abstract of DOI:10.1021/acscatal.5b01896

The redox-neutral direct coupling of arylphosphine oxides with heterobicyclic alkenes proceeds smoothly under rhodium(III) catalysis involving hydroarylation followed by dehydrative aromatization to form biarylphosphine oxides. Related phenylphosphinic and phenylphosphonic esters as well as phenylphosphine sulfides also undergo ortho-arylative coupling. Furthermore, phenylphosphinothioic amides can be transformed to fused dibenzophosphole derivatives through rhodium-catalyzed coupling with heterobicyclic alkenes and successive intramolecular phospha-Friedel-Crafts reaction in a one-pot manner.

Full text of DOI:10.1021/acscatal.5b01896

Subscriber access provided by UNIV OF NEBRASKA - LINCOLN
Article
Rhodium(III)-Catalyzed Direct Coupling of Arylphosphine
Derivatives with Heterobicyclic Alkenes: A Concise Route
to Biarylphosphines and Dibenzophosphole Derivatives
Yuto Unoh, Tetsuya Satoh, Koji Hirano, and Masahiro Miura
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.5b01896 • Publication Date (Web): 30 Sep 2015
Downloaded from http://pubs.acs.org on October 1, 2015
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
ACS Catalysis is published by the American Chemical Society. 1155 Sixteenth Street
N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 20
ACS Catalysis
1
2
3
4
5
6
7
8
Rhodium(III)-Catalyzed Direct Coupling of
Arylphosphine Derivatives with Heterobicyclic Alkenes:
A Concise Route to Biarylphosphines and
Dibenzophosphole Derivatives
9
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
Yuto Unoh,†,‡ Tetsuya Satoh, *,†,‡,§ Koji Hirano,† and Masahiro Miura*,†
†Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita, Osaka
565-0871, Japan
‡JST, ACT-C, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan
§Department of Chemistry, Graduate School of Science, Osaka City University, 3-3-138 Sugimoto,
Sumiyoshi-ku, Osaka 558-8585, Japan
RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required
according to the journal that you are submitting your paper to)
satoh@chem.eng.osaka-u.ac.jp; miura@chem.eng.osaka-u.ac.jp
1
ACS Paragon Plus Environment

ACS Catalysis
Page 2 of 20
1
2
3
4
5
6
7
8
9
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
ABSTRACT
The redox-neutral direct coupling of arylphosphine oxides with heterobicyclic alkenes proceeds
smoothly under rhodium(III) catalysis involving hydroarylation followed by dehydrative aromatization
to form biarylphosphine oxides. Related phenylphosphinic- and phenylphosphonic esters as well as
phenylphosphine sulfides also undergo ortho-arylative coupling. Furthermore, phenylphosphinothioic
amides can be transformed to fused dibenzophosphole derivatives through the rhodium-catalyzed
coupling with heterobicyclic alkenes and successive intramolecular phospha-Friedel-Crafts reaction in
one-pot manner.
KEYWORDS
rhodium, phosphine, phosphole, heterobicyclic alkene, C-H bond functionalization, arylation
2
ACS Paragon Plus Environment

Page 3 of 20
ACS Catalysis
1
2
INTRODUCTION
3
4
5
6
7
8
9
Various organophosphorus molecules have been utilized in pharmaceutical, agrochemical, and
organic materials fields.1 Besides, arylphosphine derivatives are versatile ligands for transition-metal
complexes in organometallic chemistry.2 Therefore, convenient methods for the precious preparation
and modification of arylphosphines and their synthetic intermediates including arylphosphine oxides
and sulfides have been continuously needed to be developed.
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
Meanwhile, transition-metal-catalyzed direct C–H bond functionalization reactions with the assistance
of a coordinating-functional group (directing group) are now regarded as atom- and step-economical
synthetic tools, because they allow the regioselective direct modification of given substrates without
prefunctionalization.3, 4 We5 and other groups6-9 have recently reported that the P=O and P=S groups in
arylphosphine oxides and sulfides act as good directing groups to lead to their catalytic
ortho-alkenylation (Scheme 1, left). Compared to such ortho-alkenylations, the ortho-arylation of
arylphosphine derivatives has been less explored,6m, 6o, 7c in spite of their importance as a straightforward
route to biarylphosphines. Various biarylphosphines are known as Buchwald-type phosphine ligands,
which are widely employed as ligands for transition-metal catalysts in numerous C–C, C–N, and C–O
bond forming cross-coupling reactions.10 In the context of our studies on the direct functionalization of
arylphosphine derivatives, we succeeded in finding that arylphosphine oxides undergo direct coupling
with 1,4-epoxydihydronaphthalenes under rhodium catalysis to produce biarylphosphine oxides via the
insertion of 1,4-epoxydihydronaphthalenes into the ortho-C–H bond (hydroarylation) and subsequent
dehydrative aromatization (Scheme 1, right).11 It was confirmed that thus obtained biarylphosphine
oxides can be readily reduced to the corresponding biarylphosphines. Furthermore, a one-pot synthesis
of dibenzophosphole derivatives has also been achieved by the sequence of direct coupling of
phenylphosphinothioic amides with 1,4-epoxydihydronaphthalenes and successive TfOH-mediated
phospha-Friedel-Crafts reaction. These new findings are described herein.
3
ACS Paragon Plus Environment

ACS Catalysis
Page 4 of 20
1
2
3
4
5
6
7
8
9
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
Scheme 1. Transition-Metal-Catalyzed Direct Functionalization of Arylphosphine Oxides
RESULTS AND DISCUSSION
First, we carried out optimization studies using dicyclohexylphenylphosphine oxide (1a) and
1,4-epoxydihydronaphthalene (2a) as model substrates (Table 1). Thus, 1a (0.25 mmol) was treated
with 2a (0.25 mmol) in the presence of [Cp*Rh(MeCN)3(SbF6)2] (0.01 mmol, 4 mol %) and AgOAc
(0.05 mmol, 20 mol %) in DCE at 120 °C under N2 for 12 h. As a result, the desired ortho-arylated
product 3a was formed in 60% GC yield (entry 1). As additive, Cu(OAc)2•H2O and Ag2CO3 in place of
AgOAc were not suitable (entries 2 and 3). A neutral rhodium complex, [Cp*RhCl2]2, did not show any
catalytic activity (entry 4). A combination of [Cp*RhCl2]2 and AgSbF6, which appears to form a cationic
rhodium species in situ, was less effective than [Cp*Rh(MeCN)3(SbF6)2] (entry 5). Increasing the
amount of 2a (1.5 equiv) improved the product yield up to 69% (entry 6). Addition of 3 equiv of acetic
acid or pivalic acid in place of AgOAc was found to be comparably effective (entries 7 and 8). Finally,
3a was obtained in 78% isolated yield by using 1.2 equiv of 2a at 130 °C (entry 9).
4
ACS Paragon Plus Environment

Page 5 of 20
ACS Catalysis
1
2
3
4
5
Table 1. Optimization Studies for the Rh-Catalyzed Direct Naphthylation of
Dicyclohexylphenylphosphine Oxide (1a)a
6
7
8
9
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
a
b
Reaction conditions: 1a (0.25 mmol) in DCE (2 mL) under N2 for 12 h. GC yield. Yield after
purification is given in parentheses. c At 130 °C.
With the optimized conditions in hand (entry 9 in Table 1), we investigated the substrate scope of this
reaction (Table 2). Halogen-substituted alkenes 2b and 2c smoothly coupled with 1a to give 3b and 3c
in good yields. In these cases, as well as in some other reactions described below, mixtures of
naphthylated 3 and oxabicyle retained 4 were formed. Therefore, the crude products were treated with
trimethylsilyl chloride/NaI in MeCN to convert partially formed 4 to 3. In contrast, methoxy-substituted
2d underwent fast ring-opening isomerization to fail to form expected 3d in any amount. While
diethylphenylphosphine oxide (1e) and 2,3-dihydro-4-methyl-1-phenyl-1H-phosphole oxide (1f) reacted
with 2a in a similar manner to give 3e and 3f, the sterically less hindered dimethylphenylphosphine
5
ACS Paragon Plus Environment

ACS Catalysis
Page 6 of 20
oxide (1g) underwent 1:2 coupling under conditions with 2.4 equiv of 2a to produce 3g in 60% yield.
The reactions of ortho-methyl- and ortho-phenyl-substituted dicyclohexylphenylphophine oxides 1h and
1i were somewhat sluggish, probably due to steric reasons. In the latter case, 6-arylated product 3i was
exclusively obtained, no 2’-arylation being observed. It should be noted that the direct arylation of the
same substrate 1i is known to take place at the 2’-position under palladium catalysis.6m The reactions of
di- and triarylphosphine oxides with 2a were carried out using them in a 2:1 ratio to suppress the
formation of multi-arylated products. Thus, cyclohexyldiphenylphosphine oxide (1j), para- (1k-m) and
ortho- (1n) substituted triphenylphosphine oxides, and tris(2-thienyl)phosphine oxide (1o) underwent
monoarylation to afford the corresponding products 3j-o selectively. The arylation of
5-phenyl-5H-dibenzophosphole oxide (1p) occurred not on the dibenzophosphole ring but on the phenyl
moiety, probably because of favorable geometry of the phenyl C–H bond toward the metal center. In
addition to phosphine oxides, methyl diphenylphosphinate (1q) and diethyl o-tolylphosphonate (1r) also
underwent arylation. However, these substrates were less reactive and required the addition of a
stoichiometric amount of AgOAc. Dicyclohexylphenylphosphine sulfide (1s) coupled with 2a under
standard conditions to give arylated product 3s in only 8% yield. The use of 3 equiv of AcOH in place
of AgOAc improved the yield of 3s to 39%. The silver salt additive does not seem to be suitable for the
reaction because of its strong thiophilicity.5c, 12a Interestingly, the reactions of phenylphosphonamides 1t
and 1u with 2a gave bicyclic scaffold-retained products 4t and 4u selectively in good yields.
1
2
3
4
5
6
7
8
9
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. Reaction of Arylphosphine Derivatives 1 with 1,4-Epoxydihydronaphthalene 2a
6
ACS Paragon Plus Environment

Page 7 of 20
ACS Catalysis
1
2
3
4
5
6
7
8
9
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
7
ACS Paragon Plus Environment

ACS Catalysis
Page 8 of 20
1
2
3
4
a
Reaction conditions: 1 (0.25 mmol), 2 (0.3 mmol), [Cp*Rh(MeCN)3][SbF6]2 (0.01 mmol), AgOAc
b
(0.05 mmol), in DCE (2 mL) at 130 °C under N2 for 12 h. Isolated yields are shown. The resulting
crude mixture was treated with TMSCl (0.5 mmol) and NaI (0.5 mmol) in MeCN (3 mL) at 80 oC for 12
h. c 2 (0.5 mmol) was used. d 1 (0.5 mmol) and 2 (0.25 mmol) were used. e AgOAc (0.5 mmol) was used.
f AcOH (0.75 mmol) was used in place of AgOAc.
5
6
7
8
9
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
Phenylphosphonamide 1t also reacted with N-Boc-bridged alkene 5 to produce azabicycle-retained
compound 6 in 61% yield (eq 1).
Next, we examined the reduction of product 3a to transform to the corresponding biarylphosphine.
Thus, 3a was treated with HSiCl3 in refluxing toluene to afford Buchwald-type dialkylbiarylphosphine 7
(eq 2). This sequence is effective for the synthesis of biarylphoshine derivatives from simple
arylphosphine oxides.
To demonstrate further utility of this Rh catalysis, we next attempted to combine the present arylation
of 3 with a phospha-Friedel-Crafts type cyclization to produce dibenzophosphole derivatives. It is worth
noting that benzo-fused phospholes have recently attracted much attention in the field of organic
materials because of their unique optoelectronic properties, and the straightforward synthesis of these
molecules has become an important challenge.12, 13 It is known that phosphinothioic amides undergo
Friedel-Crafts type P-arylation with simple arenes in the presence of an appropriate Lewis acid.14
8
ACS Paragon Plus Environment

Page 9 of 20
ACS Catalysis
Therefore, we envisaged that if phenylphosphinothioic amides couple with 2 to form ortho-naphthylated
products, they may undergo Friedel-Crafts type cyclization. Consequently, we treated
N,N-diethyldiphenylphosphinothionic amide (8a) (0.5 mmol) with alkene 2a (0.25 mmol) under the
conditions used for the reaction of phosphine sulfide 3s in Table 2. Then, TfOH (0.5 mL) was added and
1
2
3
4
5
6
7
8
9
o
heated at 100 C for 12 h to complete the cyclization. Finally, the resulting mixture was treated with
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
mCPBA for oxygenation on the phosphorus atom to provide 11-phenyldibenzo[b,g]phosphindole
11-oxide (9a) in 62% yield (Table 3). The same one-pot procedure could be applied to the reactions
using a number of phosphinothioic amides and alkenes to produce a series of dibenzophosphole oxides
9b-f. A related diphenylphosphinamide (1v) also underwent phaspha-Friedel-Crafts reaction, albeit with
a poor yield (eq 3). It should be noted that the reaction starting from 8a under previously reported
AlCl3-mediated Friedel-Crafts conditions14 gave a mixture of products cyclized at the α- and β-naphthyl
positions. In contrast, our TfOH-mediated conditions gave exclusively the α-cyclized product.15 In a
recently reported naphthalene-fused benzophosphole synthesis by means of Pd-catalyzed direct
coupling,13d, 13g the α/β-selectivity has been found to be sterically controlled. Thus, our methodology is
complimentary to the previous report.
Table 3. One-pot Synthesis of Dibenzophophole oxides 9 by Rh(III)-catalyzed Direct
Naphthylation–Intramoleculer Phospha-Friedel-Crafts Reaction of Arylphosphinothioic Amide 8a
9
ACS Paragon Plus Environment

ACS Catalysis
Page 10 of 20
1
2
3
4
5
6
7
8
9
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
a
Reaction conditions: 1) 8 (0.5 mmol), 2 (0.25 mmol), [Cp*Rh(MeCN)3][SbF6]2 (0.01 mmol), AcOH
(0.75 mmol), in DCE (2 mL) at 130 °C under N2 for 12 h; 2) TfOH (0.5 mL) at 100 °C under N2 for 12
h; 3) mCPBA, rt. Isolated yields are shown.
To obtain mechanistic insight, a number of additional experiments were performed. At the early stage
of the reaction of 1a with 2a under standard conditions, a significant amount of 4a (64%) was formed
together with 3a (16%) (eq 4). Further treatment of the mixture led to the complete disapperance of once
formed 4a and selective formation of 3a. Thus, 4a is considered to be the initial principal product. A
plausible mechanism for the formation of 4 from phenylphosphine oxide 1 with oxabicyclic alkene 2 is
illustrated in Scheme 2. Coordination of the P=O directing group of 1 to the metal center of catalyst
forms a cationic Rh(III) intermediate A followed by C-H bond cleavage at the ortho-position of A takes
place to yield a five-membered rhodacycle intermediate B. Then, the alkene insertion and subsequent
protonolysis of a resulting intermediate C may occur to produce oxabicycle-retained product 4. Further
heating may induce dehydrative aromatization to afford biarylphosphine oxide 3. β-Oxygen elimination
10
ACS Paragon Plus Environment

Page 11 of 20
ACS Catalysis
in the intermediate C leading to the ring-opening could occur, if any, only to a minor extent.11a
1
2
3
4
5
6
7
8
9
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
Scheme 2. Plausible Reaction Mechanism
Next, some deuterium labeling studies were also conducted. As shown in eq 4, the reaction of 1a with
11
ACS Paragon Plus Environment

ACS Catalysis
Page 12 of 20
2a gave a mixture of 3a and 4a at the early stage. Therefore, we chose 1t as a model substrate for
simplification, because the reaction of 1t with 2a gave only 4t (Table 2). When 1t-d5 was treated in the
presence of 3 equiv of acetic acid for 15 min, no D/H scrambling was observed in recovered 1t-d5 as
well as formed 4t-d4 (eq 5). Furthermore, significant kinetic isotope effects (KIE) were observed in
parallel and competitive reactions of 1t and 1t-d5 (eqs 6/7 and 8). These results suggest the C‒H bond
1
2
3
4
5
6
7
8
9
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
cleavage step is most likely irreversible and rate-limiting.
12
ACS Paragon Plus Environment

Page 13 of 20
ACS Catalysis
1
2
3
4
5
6
7
8
9
In addition, we investigated relative reactivity between phosphine oxide 1a and phosphinamide 1t (eq
9). In a competitive experiment with 2a, 1t reacted more smoothly than 1a. Furthermore, a significant
amount of aromatized 3t was also formed, in contrast to the independent reaction in which only a trace
amount of 3t was observed as described above.
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
Based on the result of eq 9, we examined the effect of a phosphine oxide additive. When 20 mol% of
O=PCy3 was added to the reaction of 1t with 2a under standard conditions, 4t and 3t were formed in
87% and 9% yields, respectively (eq 10). Increasing the amount of O=PCy3 to 1 equiv enhanced the
yield of 3t to 22%, while the total yield of 3t and 4t was somewhat lower. Although the exact role of the
added phosphine oxide is unclear at this stage, these results indicate that a phosphine oxide can promote
the dehydrative aromatization of 4t.
CONCLUSION
13
ACS Paragon Plus Environment

ACS Catalysis
Page 14 of 20
We have demonstrated that the rhodium-catalyzed redox-neutral direct ortho-arylation of
arylphosphine derivatives with heterobicyclic alkenes can be conducted efficiently. A number of biaryl
phosphine derivatives could be obtained from simple aryl phosphine oxides. Furthermore, the
1
2
3
4
5
6
7
8
combination
of
rhodium-catalyzed
ortho-arylation
and
acid-mediated
intramolecular
9
phospha-Friedel-Crafts reaction enables the concise synthesis of dibenzophosphole derivatives from
readily available diarylphosphinothionic amides in one-pot mammer. Further development of the direct
functionalization of organophosphorus compounds is now in progress in our laboratory.
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
EXPERIMENTAL SECTION
General Procedures for Rh(III)-catalyzed Coupling of Phosphine Derivatives with
Heterobicyclic Alkenes. In a 10 mL sealable tube, the indicated amounts of 1 and 2a in Table 2,
[Cp*Rh(MeCN)3(SbF6)2] (8.3 mg, 0.01 mmol), and AgOAc (8.4 mg, 0.05 mmol) were placed with a
magnetic stir bar under N2 atmosphere. Then, DCE (2 mL) was added by a syringe. The reaction
mixture was heated at 130 °C in an oil bath for 12 h. After cooling, the reaction was quenched with 10
mL of water and extracted three times with DCM (20 mL x 3). The combined organic layer was dried
over Na2SO4 and volatiles were removed in vacuo. [If necessary, the resulting residue was treated with
NaI (74.9 mg, 0.5 mmol) and TMSCl (54.3 mg, 0.5 mmol) in MeCN (3 mL) at 80 °C under N2
atmosphere for overnight. After cooling, the reaction was quenched with sat. NaHCO3 and sat. Na2S2O3
and extracted three times with DCM (20 mL x 3). The combined organic layer was dried over Na2SO4
and volatiles were removed in vacuo.] The residue was purified by column chromatography on silica gel
to give product.
Synthesis of Benzo[b]phosphole Derivatives by One-Pot Rh-catalyzed Coupling and
phospha-Friedel-Crafts Reaction. In a 10 mL sealable tube, 8 (0.5 mmol), 2 (0.25 mmol), and
[Cp*Rh(MeCN)3(SbF6)2] (8.3 mg, 0.01 mmol) were placed with a magnetic stir bar under N2
atmosphere. Then DCE (2 mL) and AcOH (43 µl, 0.75 mmol) were added by a syringe. The reaction
14
ACS Paragon Plus Environment

Page 15 of 20
ACS Catalysis
mixture was heated at 130 °C in an oil bath for 12 h. After cooling, TfOH (0.5 mL) was added by a
syringe. The resulting mixture was heated up again to 100 °C for 12 h. After cooling, the reaction
mixture was poured into sat. NaHCO3, and extracted three times with DCM (20 mL x 3). The combined
organic layer was dried over Na2SO4 and volatiles were removed under reduced pressure. The obtained
mixture was dissolved in DCM (5 mL) again, and mCPBA (~70 wt%, 130 mg, ~0.5 mmol) was slowly
added and stirred for a few minutes. After checking the full conversion of phosphole sulfide on TLC,
the reaction was quenched by sat. NaHCO3 and sat. Na2S2O3. Subsequently the crude material was
extracted three times with DCM (20 mL x 3). The combined organic layer was dried over Na2SO4 and
volatiles were removed under reduced pressure. The desired product was obtained after purification by
column chromatography on silica gel.
1
2
3
4
5
6
7
8
9
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
ASSOCIATE CONTENT
Supporting Information
Supporting Information Available: Detailed experimental procedures, additional data, analytical data,
1
and H, C, F and P NMR spectra. This material is available free of charge via the Internet at
13
19
31
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
*E-mail: satoh@chem.eng.osaka-u.ac.jp.
*E-mail: miura@chem.eng.osaka-u.ac.jp.
Notes
The authors declare no competing financial interest.
15
ACS Paragon Plus Environment

ACS Catalysis
Page 16 of 20
ACKNOWLEDGMENT
1
2
3
4
5
This work was supported by Grants-in-Aid for Scientific Research from the MEXT, JSPS, and JST,
Japan.
6
7
8
9
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
REFERENCES
(1) (a) Baumgartner, T.; Réau, R. Chem. Rev. 2006, 106, 4681-4727. (b) Van der Jeught, S.; Stevens,
C. V. Chem. Rev. 2009, 109, 2672-2702. (c) Demmer, C. S.; Krogsgaard-Larsen, N.; Bunch, L. Chem.
Rev. 2011, 111, 7981-8006. (d) Queffelec, C.; Petit, M.; Janvier, P.; Knight, D. A.; Bujoli, B. Chem. Rev.
2012, 112, 3777-3807. (e) Montchamp, J.-L. Acc. Chem. Res. 2014, 47, 77. (f) Baumgartner, T. Acc.
Chem. Res. 2014, 47, 1613-1622.
(2) (a) Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000, 33, 336-345. (b) McCarthy, M.; Guiry, P. J.
Tetrahedron 2001, 57, 3809-3844. (c) Tang, W.; Zhang, X. Chem. Rev. 2003, 103, 3029-3070. (d)
Kollár, L.; Keglevich, G. Chem. Rev. 2010, 110, 4257-4302. (e) Fernandez-Perez, H.; Etayo, P.;
Panossian, A.; Vidal-Ferran, A. Chem. Rev. 2011, 111, 2119-2176. (f) Verendel, J. J.; Pamies, O.;
Dieguez, M.; Andersson, P. G. Chem. Rev. 2014, 114, 2130-2169.
(3) For pioneering work, see: Murai, S.; Kakiuchi, F.; Sekine, S.; Tanaka, Y.; Kamatani, A.; Sonoda,
M.; Chatani, N. Nature 1993, 366, 529-531.
(4) Selected recent reviews for C−H functionalization: (a) Dyker, G. Angew. Chem., Int. Ed. 1999, 38,
1698-1712. (b) Kakiuchi, F.; Chatani, N. Adv. Synth. Catal. 2003, 345, 1077-1101. (c) Godula, K.;
Sames, D. Science 2006, 312, 67-72. (d) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107,
174-238. (e) Beccalli, E. M.; Broggini, G.; Martinelli, M.; Sottocornola, S. Chem. Rev. 2007, 107,
5318-5365. (f) Park, Y. J.; Park, J.-W.; Jun, C.-H. Acc. Chem. Res. 2008, 41, 222-234. (g) Ferreira, E.
M.; Zhang, H.; Stoltz, B. M. Tetrahedron 2008, 64, 5987-6001. (h) Kakiuchi, F.; Kochi, T. Synthesis
16
ACS Paragon Plus Environment

Page 17 of 20
ACS Catalysis
2008, 3013-3039. (i) Li, C.-J. Acc. Chem. Res. 2009, 42, 335-344. (j) McGlacken, G. P.; Bateman, L. M.
Chem. Soc. Rev. 2009, 38, 2447-2464. (k) Daugulis, O.; Do, H.-Q.; Shabashov, D. Acc. Chem. Res.
2009, 42, 1074-1086. (l) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem., Int. Ed. 2009,
48, 5094-5115. (m) Satoh, T.; Miura, M. Synthesis 2010, 3395-3409. (n) Satoh, T.; Miura, M. Chem.
Eur. J. 2010, 16, 11212-11222. (o) Sun, C.-L.; Li, B.-J.; Shi, Z.- J. Chem. Commun. 2010, 46, 677-685.
(p) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624-655. (q) Lyons, T. W.;
Sanford, M. S. Chem. Rev. 2010, 110, 1147-1169. (r) Lapointe, D.; Fagnou, K. Chem. Lett. 2010, 39,
1118-1126. (s) Ackermann, L. Chem. Rev. 2011, 111, 1315-1345. (t) Liu, C.; Zhang, H.; Shi, W.; Lei, A.
Chem. Rev. 2011, 111, 1780-1824. (u) Kuninobu, Y.; Takai, K. Chem. Rev. 2011, 111, 1938-1953. (v)
Wencel-Delord, J.; Droge, T.; Liu, F.; Glorius, F. Chem. Soc. Rev. 2011, 40, 4740-4761. (w) Cho, S. H.;
Kim, J. Y.; Kwak, J.; Chang, S. Chem. Soc. Rev. 2011, 40, 5068-5083. (x) Mitchell, E. A.; Peschiulli,
A.; Lefevre, N.; Meerpoel, L.; Maes, B. U. W. Chem. Eur. J. 2012, 18, 10092-10142. (y) Engle, K. M.;
Mei, T.-S.; Wasa, M.; Yu, J.-Q. Acc. Chem. Res. 2012, 45, 788-802. (z) Colby, D. A.; Tsai, A. S.;
Bergman, R. G.; Ellman, J. A. Acc. Chem. Res. 2012, 45, 814-825. (aa) Patureau, F. W.; Wencel-Delord,
J.; Glorius, F. Aldrichimica Acta 2012, 45, 31-49. (ab) Chiba, S. Chem. Lett. 2013, 41, 1554-1559. (ac)
Wencel-Delord, J.; Glorius, F. Nat. Chem. 2013, 5, 369-375. (ad) Engle, K. M.; Yu, J.-Q. J. Org. Chem.
2013, 78, 8927-8955. (ae) Miura, M.; Satoh, T.; Hirano, K. Bull. Chem. Soc. Japan. 2014, 87, 751-764.
(af) De Sarkar, S.; Liu, W.; Kozhushkov, S. I.; Ackermann, L. Adv. Synth. Catal. 2014, 356, 1461-1479.
(ag) Kuhl, N.; Schröder, N.; Glorius, F. Adv. Synth. Catal. 2014, 356, 1443-1460. (ah) Song, G.; Li, X.
Acc. Chem. Res. 2015, 48, 1007-1020. (ai) Chen, Z.; Wang, B.; Zhang, J.; Yu, W.; Liu, Z.; Zhang, Y.;
Org. Chem. Front., 2015, 2, 1107-1295.
1
2
3
4
5
6
7
8
9
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
(5) (a) Unoh, Y.; Hashimoto, Y.; Takeda, D.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2013, 15,
3258-3261. (b) Itoh, M.; Hashimoto, Y.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2013, 78,
8098-8104. (c) Yokoyama, Y.; Unoh, Y.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2014, 79,
17
ACS Paragon Plus Environment

ACS Catalysis
Page 18 of 20
7649-7655.
1
2
3
4
5
6
7
8
9
(6) Pd catalysis: (a) Meng, X.; Kim, S. Org. Lett. 2013, 15, 1910-1913. (b) Chan, L. Y.; Kim, S.; Ryu,
T.; Lee, P. H. Chem. Commun. 2013, 49, 4682-4684. (c) Chan, L. Y.; Cheong, L.; Kim, S. Org. Lett.
2013, 15, 2186-2189. (d) Chan, L. Y.; Meng, X.; Kim, S. J. Org. Chem. 2013, 78, 8826-8832. (e) Meng,
X.; Kim, S. J. Org. Chem. 2013, 78, 11247-11254. (f) Chary, B. C.; Kim, S.; Park, Y.; Kim, J.; Lee, P.
H. Org. Lett. 2013, 15, 2692-2695. (g) Wang, H.-L.; Hu, R.-B.; Zhang, H.; Zhou, A.-X.; Yang, S.-D.
Org. Lett. 2013, 15, 5302-5305. (h) Zhang, H.-Y.; Yi, H.-M.; Wang, G.-W.; Yang, B.; Yang, S.-D. Org.
Lett. 2013, 15, 6186-6189. (i) Jeon, W. H.; Lee, T. S.; Kim, E. J.; Moon, B.; Kang, J. Tetrahedron 2013,
69, 5152-5159. (j) Eom, D.; Jeong, Y.; Kim, Y. R.; Lee, E.; Choi, W.; Lee, P. H. Org. Lett. 2013, 15,
5210-5213. (k) Wang, H.-L.; Hu, R.-B.; Zhang, H.; Zhou, A.-X.; Yang, S.-D. Org. Lett. 2013, 15,
5302-5305. (l) Shin, S.; Jeong, Y.; Jeon, W. H.; Lee, P. H. Org. Lett. 2014, 16, 2930-2933. (m) Hu,
R.-B.; Zhang, H.; Zhang, X.-Y.; Yang, S.-D. Chem. Commun. 2014, 50, 2193-2195. (n) Zhang, H.; Hu,
R.-B.; Zhang, X.-Y.; Li, S.-X.; Yang, S.-D. Chem. Commun. 2014, 50, 4686-4689. (o) Guan, J.; Wu,
G.-J.; Han, F. S. Chem.—Eur. J. 2014, 20, 3301-3305. (p) Shin, S.; Kang, D.; Jeon, W. H.; Lee, P. H.
Beilstein J. Org. Chem. 2014, 10, 1220-1227. (q) Du, Z.-J.; Guan, J.; Wu, G. J.; Xu, P.; Gao, L. X.; Han,
F. S. J. Am. Chem. Soc. 2015, 137, 632-635. (r) Jeon, W. H.; Son, J.-Y.; Kim, S.-E.; Lee, P. H. Adv.
Synth. Catal. 2015, 357, 811-817. (s) Ma, Y.-N.; Zhang, H.-Y.; Yang, S.-D. Org. Lett. 2015, 17,
2034-2037.
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
(7) Rh catalysis: (a) Seo, J.; Park, Y.; Jeon, I.; Ryu, T.; Park, S.; Lee, P. H. Org. Lett. 2013, 15,
3358-3361. (b) Ryu, T.; Kim, J.; Park, Y.; Kim, S.; Lee, P. H. Org. Lett. 2013, 15, 3986-3989. (c) Zhao,
D.; Nimphius, C.; Lindale, M.; Glorius, F. Org. Lett. 2013, 15, 4504-4507. (d) Park, Y.; Seo, J.; Park,
S.; Yoo, E. J.; Lee, P. H. Chem.—Eur. J. 2013, 19, 16461-16468. (e) Park, S.; Seo, B.; Shin, S.; Son,
J.-Y.; Lee, P. H. Chem. Commun. 2013, 49, 8671-8673. (f) Mo, J.; Lim, S.; Ryu, T.; Kim, S.; Lee, P. H.
RSC Adv. 2013, 3, 18296-18299. (g) Chary, B. C.; Kim, S. Org. Biomol. Chem. 2013, 11, 6879-6882.
18
ACS Paragon Plus Environment

Page 19 of 20
ACS Catalysis
(h) Liu, L.; Wu, Y.; Wang, T.; Gao, X.; Zhu, J.; Zhao, S. J. Org. Chem. 2014, 79, 5074-5081. (i) Gu,
L.-J.; Jin, C.; Wang, R.; Ding, H.-Y. ChemCatChem 2014, 6, 1225-1228.
1
2
3
4
5
(8) Ru catalysis: Park, Y.; Jeon, I.; Shin, S.; Min, J.; Lee, P. H. J. Org. Chem. 2013, 78, 10209-10220.
6
7
8
9
(9) Ir catalysis: Gwon, D.; Lee, D.; Kim, J.; Park, S.; Chang, S. Chem.—Eur. J. 2014, 20,
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
12421-12425.
(10) (a) Martin, R.; Buchwald, S. L. Acc. Chem. Res. 2008, 41, 1461-1473. (b) Surry, D. S.; Buchwald,
S. L. Angew. Chem., Int. Ed. 2008, 47, 6338-6361. (c) Surry, D. S.; Buchwald, S. L. Chem. Sci. 2011, 2,
27-50. (d) Hoshiya, N.; Buchwald, S. L. Adv. Synth. Catal. 2012, 354, 2031-2037.
(11) Relevant catalytic C-H functionalization reactions with bicyclic alkenes, see: (a) Qi, Z.; Li, X.
Angew. Chem., Int. Ed. 2013, 52, 8995-9000. (b) Yang, T.; Zhang, T.; Yang, S.; Chen, S.; Li, X. Org.
Biomol. Chem. 2014, 12, 4290-4294. (c) Dong, W.; Parthasarathy, K.; Cheng, Y.; Pan, F.; Bolm, C.
Chem.—Eur. J. 2014, 20, 15732-15736. (d) Cheng, H.; Dong, W.; Dannenberg, C. A.; Dong, S.; Guo,
Q.; Bolm, C. ACS Catal., 2015, 5, 2770-2773.
(12) (a) Unoh, Y.; Hirano, K.; Satoh, T.; Miura, M. Angew. Chem., Int. Ed. 2013, 52, 12975-12979.
See also: (b) Chen, Y.; Duan, W. J. Am. Chem. Soc. 2013, 135, 16754-16757. (c) Ma, W.; Ackermann,
L. Synthesis 2014, 46, 2297-2304.
(13) (a) Matano, Y.; Imahori, H. Org. Biomol. Chem. 2009, 7, 1258-1271. (b) Fukazawa, A.; Hara,
M.; Okamoto, T.; Son, E.-C.; Xu, C.; Tamao, K.; Yamaguchi, S. Org. Lett. 2008, 10, 913-916. (c)
Fukawa, N.; Osaka, T.; Noguchi, K.; Tanaka, K. Org. Lett. 2010, 12, 1324-1327. (d) Kuninobu, Y.;
Yoshida, T.; Takai, K. J. Org. Chem. 2011, 76, 7370-7376. (e) Matano, Y.; Saito, A.; Fukushima, T.;
Yokudome, Y.; Suzuki, F.; Sakamaki, D.; Kaji, H.; Ito, A.; Tanaka, K.; Imahori, H. Angew. Chem., Int.
Ed. 2011, 50, 8016-8020. (f) Bruch, A.; Fukazawa, A.; Yamaguchi, E.; Yamaguchi, S.; Studer, A.
Angew. Chem., Int. Ed. 2011, 50, 12094-12098. (g) Baba, K.; Tobisu, M.; Chatani, N. Angew. Chem.,
19
ACS Paragon Plus Environment

ACS Catalysis
Page 20 of 20
Int. Ed. 2013, 52, 11892-11895. (h) Cui, Y.; Fu, L.; Cao, J.; Deng, Y.; Jiang, J. Adv. Synth. Catal. 2014,
356, 1217-1222. (i) Furukawa, S.; Haga, S.; Kobayashi, J.; Kawashima, T. Org. Lett. 2014, 16,
3228-3231. (j) Baba, K.; Tobisu, M.; Chatani, N. Org. Lett., 2015, 17, 70-73.
1
2
3
4
5
6
7
8
9
(14) (a) Olah, G. A.; Hehemann, D. J. Org. Chem. 1977, 42, 2190-2190. (b) Wang, Z.-W.; Wang, L.-S.
Green Chem. 2003, 5, 737-739. (c) Diaz, A. A.; Young, J. D.; Khan, M. A.; Wehmschulte, R. J. Inorg.
Chem. 2006, 45, 5568-5575. (d) Diaz, A. A.; Buster, B.; Schomich, D.; Khan, M. A.; Baum, J. C.;
Wehmschulte, R. J. Inorg. Chem. 2008, 47, 2858-2863. (e) Hatakeyama, T.; Hashimoto, S.; Nakamura,
M. Org. Lett. 2011, 13, 2130-2133. (f) Hashimoto, S.; Nakatsuka, S.; Nakamura, M.; Hatakeyama, T.
Angew. Chem., Int. Ed. 2014, 53, 14074-14076.
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
(15) See the Supporting Information for the details of optimization studies.
20
ACS Paragon Plus Environment