Asymmetric Alkylation of N-Sulfonylbenzamides with Vinyl Ethers via C-H Bond Activation Catalyzed by Hydroxoiridium/Chiral Diene Complexes

Article abstract of DOI:10.1021/jacs.6b01591

Asymmetric alkylation of N-sulfonylbenzamides with vinyl ethers via a directed C-H bond activation gave high yields of the corresponding addition products with high branch- and enantioselectivity.

Full text of DOI:10.1021/jacs.6b01591

Subscriber access provided by GAZI UNIV
Communication
Asymmetric Alkylation of N-Sulfonylbenzamides with Vinyl Ethers via C-
H Bond Activation Catalyzed by Hydroxoiridium/Chiral Diene Complexes
Miyuki Hatano, Yusuke Ebe, Takahiro Nishimura, and Hideki Yorimitsu
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.6b01591 • Publication Date (Web): 10 Mar 2016
Downloaded from http://pubs.acs.org on March 10, 2016
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.
Journal of the American Chemical Society 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 5
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
Asymmetric Alkylation of N-Sulfonylbenzamides with Vinyl Ethers
via C–H Bond Activation Catalyzed by Hydroxoiridium/Chiral
Diene Complexes
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
Miyuki Hatano, Yusuke Ebe, Takahiro Nishimura,* and Hideki Yorimitsu
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
Supporting Information Placeholder
Scheme 1. Ir-Catalyzed Branch-Selective Alkylation with
Vinyl Ethers
ABSTRACT:
Asymmetric
alkylation
of
N-
sulfonylbenzamides with vinyl ethers via a directed C–H
bond activation gave high yields of the corresponding
addition products with high branch- and enantioselec-
tivity.
Direct functionalization of aromatic compounds via C–H
bond activation of unactivated aromatic rings is emerg-
ing as one of the most desirable methodologies of the
atom- and step-economical synthesis of useful com-
pounds in organic chemistry.1 A large number of cata-
lytic systems using transition metal complexes have
been developed for the direct carbon-carbon bond for-
mation of aromatic compounds. The ortho-selective
alkylation has been achieved by use of directing groups,
and in most cases of the alkylation with alkenes, a linear
selectivity has been successfully presented.2 On the oth-
er hand, a branch-selective alkylation,3 which enables an
asymmetric construction of benzylic stereocenters, has
also been recently developed in the reaction of vinyl
arenes4 and simple alkenes,5 but the asymmetric variant
of the reaction involving the C–H bond activation re-
mains significantly underdeveloped.6,7 In this respect,
we recently reported a branch-selective alkylation of
aromatic compounds with a variety of alkyl and aryl
vinyl ethers,8,9 where a cationic Ir complex catalyzes the
reaction of aromatic compounds having nitrogen-based
directing groups such as 2-pyridyl, 2-benzothiazolyl, 2-
oxazolyl, and imino groups (Scheme 1a). We also pre-
sented preliminary promising results of the enantioselec-
tive alkylation of 2-phenylpyridine with vinyl ethers,
although the enantioselectivity is modest (77% ee). In
terms of synthetic utility, the use of simple and convert-
ible directing groups is desirable, and thus we next fo-
cused on an aromatic amide that can form an amidoirid-
ium(I) species as an active intermediate for the ortho C–
H activation (Scheme 1b). Here we report the asymmet-
ric direct alkylation of N-sulfonyl aromatic amides10
with vinyl ethers. The reaction was efficiently catalyzed
by a hydroxoiridium complex without adding any bases
or additives. The use of a chiral diene ligand enabled
the enantioselective alkylation to give the corresponding
products in high yields with high branch- and enantiose-
lectivity.
We found that a hydroxoiridium complex can catalyze
the alkylation of N-sulfonylbenzamides with vinyl ethers
with high branch-selectivity. Thus, treatment of 3-
methyl-N-(methanesulfonyl)benzamide (1a) with 1.5
equiv of butyl vinyl ether (2a) in the presence of
[Ir(OH)(cod)]2 (5 mol % Ir, cod = 1,5-cyclooctadiene) in
toluene at 80 ºC for 20 h gave an 84% yield of branched
adduct 3aa as a sole addition product (Table 1, entry 1).
The reaction was not catalyzed by a chloroiridium com-
plex [IrCl(cod)]2 (entry 2) and a cationic complex
formed from [IrCl(cod)]2 and NaBArF [ArF = 3,5-
4
(CF3)2C6H3] (entry 3), the latter of which displayed a
high catalytic activity in the alkylation of 2-
phenylpyridines.8 These results indicate that an ami-
doiridium species formed from the hydroxoiridium
complex with benzamide 1a is a key intermediate as
shown in Scheme 1b.11,12 A hydroxorhodium complex
[Rh(OH)(cod)]2 showed no catalytic activity for the re-
action (entry 4). The use of chiral diene ligands13 ena-
bled the asymmetric variant of the reaction. Chiral diene
ligands based on a tetrafluorobenzobarrelene (tfb)
ACS Paragon Plus Environment

Journal of the American Chemical Society
Table 1. Ir-Catalyzed Alkylation of 1 with 2aa Table 2. Scope of Vinyl Ethers 2a
Page 2 of 5
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
entry
2
3
yield (%)b
ee (%)c
96
entry
[M]
1
yield
(%)
ee
(%)
1
2a
3aa
97
89
96
97
91
94
71
86
70
97
2
3d
2b
2c
2d
2e
2f
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
97
1
[Ir(OH)(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2/NaBArF
1a 84
–
96
2
3b
1a
1a
1a
0
0
0
–
4
97
–
4
5
97
4
[Rh(OH)(cod)]2
–
6
96
5
[Ir(OH)((S,S)-Me-tfb*)]2 1a 94
[Ir(OH)((S,S)-Bn-tfb*)]2 1a 71
96
95
94
94
42
97
–
7
2g
2h
2i
83
6
8e
9f
10
96
7
[Ir(OH)((S,S)-Ph-tfb*)]2
[Ir(OH)((S,S)-Fc-tfb*)]2
1a 74
1a 93
93
8
2j
3aj
92
9
[Ir(OH)(cod)]2/(R)-binap 1a 11
aReaction conditions: 1a (0.20 mmol), 2a (0.30 mmol),
[Ir(OH)((S,S)-Me-tfb*)]2 (5 mol % of Ir) in toluene (0.80
mL) at 70 °C for 20 h. bIsolated yield. cDetermined by
HPLC analysis. For 3aa–3af and 3ah, the ee values were
determined by HPLC analysis of N-mesyl-N-
methylbenzamides 4 derived from 3. dPerformed with 3
10
11
12
[Ir(OH)((S,S)-Me-tfb*)]2 1b
[Ir(OH)((S,S)-Me-tfb*)]2 1c
6
0
0
[Ir(OH)(cod)]2
1d
–
aReaction conditions: 1 (0.10 mmol), 2a (0.15 mmol),
[M] (5 mol %) in toluene (0.40 mL) at 80 °C (entries 1–4)
e
f
equiv of 2c. For 48 h. With 10 mol % of Ir.
b
or at 70 °C (entries 5–12) for 20 h. Performed with NaB-
ArF
(10 mol %).
Hydroxoiridium complexes
The hydroxoiridium/Me-tfb* complex displayed high
catalytic activity and enantioselectivity in the alkylation
of N-mesylbenzamide 1a with diverse vinyl ethers (Ta-
ble 2). Alkyl vinyl ethers 2a–h participated in the alkyl-
ation of 1a to give high yields of the corresponding
products 3aa–3ah with 83–97% ee (entries 1–8), where
functional groups such as MeO (entry 5), Cl (entry 6),
OH (entry 7), and internal alkene moieties (entry 8) were
tolerated. The alkylation with phenyl vinyl ether (2i)
gave 2ai in 70% yield with 93% ee (entry 9). Cyclic
ether 2j was also applicable to the present alkylation to
give the corresponding 2-aryltetrahydrofuran 3aj in 97%
yield with 92% ee (entry 10).16 On the other hand, no
reaction of 1a was observed with tert-butyl vinyl ether
(2k), 1-octene, or styrene.
4
[Ir(OH)((S,S)-R-tfb*)]2 were generated by pre-treatment of
the IrCl(diene) complexes with KOHaq; See the Support-
ing Information for details.
framework have been recently developed in the Rh- and
Ir-catalyzed asymmetric reactions.14 Chiral tfb* ligands
substituted with Me, benzyl (Bn), Ph, and ferrocenyl
(Fc) all displayed high enantioselectivity (94–96% ee) in
the reaction of 1a with 2a at 70 °C (entries 5–8), and
Me-tfb* was selected as the ligand for further investiga-
tion (entry 5). The use of (R)-binap resulted in a low
yield of the product with low enantioselectivity (42% ee,
entry 9). An electron-deficient substituent on the amide
nitrogen of 1 greatly influenced the reactivity; me-
thanesulfonyl (1a, entry 5) displayed higher reactivity
than p-toluenesulfonyl (1b, entry 10), and a primary am-
ide 1c did not undergo the alkylation at all (entry 11). In
addition, 3,N-dimethyl-N-(methanesulfonyl)benzamide
(1d) did not show any reactivity under the present reac-
tion conditions (entry 12).15 These results indicate that
the N–H proton of 1 that has a high acidity is essential
for the formation of the amidoiridium species from the
hydroxoiridium.
Table 3 summarizes the results obtained for the reac-
tion of a variety of N-mesylbenzamides 1 with butyl
vinyl ether (2a). The ortho-alkylation of benzamides
substituted at the meta-position with MeO (1e), Br (1f),
and Cl (1g) took place at the less sterically hindered po-
sition to give high yields of the corresponding adducts
3ea–3ga with high enantioselectivity (entries 1–3). A
similar regioselectivity of the C–H activation was obser-
ved in the reaction of 1h having a less bulky fluoro
ACS Paragon Plus Environment

Page 3 of 5
Journal of the American Chemical Society
Scheme 2. Transformations of N-Mesylamides
Table 3. Asymmetric Alkylation of 1 with 2aa
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
The results of deuterium-labeling experiments
(Schemes S1–S6, eq 1) provided us with mechanistic
insights. Thus, the reaction of 1a with butyl vinyl ether
(2a) in the presence of [Ir(OH)(cod)]2 (5 mol %) and
D2O (20 equiv) at 70 °C for 0.5 h gave alkylation prod-
uct 3aa (32%), where deuterium incorporation was ob-
served for 3aa and recovered 1a and 2a (eq 1). The re-
sult indicates that C−H activation and hydrometalation
steps (from A to B1, Scheme 3) are reversible. On the
other hand, the reaction of tert-butyl vinyl ether (2k) did
not give the alkylation product 3ak, but deuterium in-
corporation into the alkene moiety of 2k was detected,
indicating that species A undergoes reversible hydro-
metalation to 2k (from A to B2). Ethyl 1-propenyl ether
(2l) had a similar reactivity to 2k. If reductive elimina-
tion from species B1 took place to give the alkylation
product 3aa, the adducts 3ak and 3al will also be
formed because there should not be a significant differ-
ence on the reactivities of species B1–3. As an alterna-
tive pathway leading to the alkylation product, an irre-
versible carbometalation is presumably involved in the
reaction (from A to C).17 It is likely that a less bulky
vinyl ether 2a undergoes carbometalation to give the
alkylation product via intermediate C1, but the carbo-
metalation to more bulky vinyl ethers 2k and 2l is inhib-
ited (from A to C2 and C3).
aReaction conditions: 1 (0.20 mmol), 2a (0.30 mmol),
[Ir(OH)((S,S)-Me-tfb*)]2 (5 mol % of Ir) in toluene (0.80
mL) at 70 °C for 20 h. Isolated yields (%) are shown. The
ee values (%) are shown in parenthesis. For 48 h. For 72
h. dThe ee was determined by HPLC analysis of N-mesyl-
N-methylbenzamides 4 derived from 3. eThe ratio of regi-
oisomers (6- and 2-alkyl). fThe ee of the major isomer.
b
c
group at the meta-position, although a small amount of
the regioisomer, which is alkylated at the 2-position, was
formed (entry 4).
The alkylation of meta,para-
disubstituted benzamides 1i–l and ortho-substituted ben-
zamides 1m–o proceeded well to give the corresponding
adducts 3ia–3oa with high enantioselectivity (entries 5–
11). Amides having naphthyl groups (1p and 1q) and
heteroaromatic rings (1r and 1s) are also good substrates
to give the corresponding adducts 3pa–3sa with 93–97%
ee (entries 12–15).
In the alkylation of N-
mesylbenzamide (1t), the formation of a considerable
amount (60%) of ortho-dialkylation product 3ta' was
observed (entry 16). On the other hand, the reaction of
amide 1u having an N-(pyrrolidin-1-ylsulfonyl) group
with 2a under the standard reaction conditions gave
monoalkylation product 3ua in 61% yield with 96% ee
with the formation of an 9% yield of dialkylation prod-
uct 3ua' (entry 17).
The alkylation of p-
CONHMs
CONHMs
1a
(0.10 mmol)
[Ir(OH)(cod)]2
(5 mol%)
D2O (20 equiv)
methylbenzamide 1v gave monoalkylation product 3va
in 53% yield with 99% ee as well as a 21% yields of
dialkylation product 3va' (entry 18).
CD3 26%
+
D 66%
BuO D 11%
3aa-d: 32%
1a-d: 67%
D 50%
(1)
C6D6
70 ºC, 0.5 h
OBu
2a
The ortho-alkylated N-mesylbenzamide obtained here
with high enantioselectivity can be converted into sever-
al chiral compounds (Scheme 2). Thus, an introduction
of a methyl group on the nitrogen atom of 3aa (96% ee)
gave 4aa, and the amide 4aa was led to ester 5, amide 6,
aldehyde 7, and alcohol 8 without loss of the enantio-
meric purity (Scheme 2a–d). Treatment of 4ae with 2,3-
dichloro-5,6-dicyano-p-benzoquinone (DDQ) gave lac-
tone 9 in 81% yield (Scheme 2e).
(0.15 mmol)
53%
D
D 49%
OBu
2a-d (0.11 mmol)
Scheme 3. A Key Step Leading to the Alkylation Product
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 5
Chem. Soc. 2010, 132, 13666. (h) Shih, W.-C.; Chen, W.-C.; Lai, Y.-
C.; Yu, M.-S.; Ho, J.-J.; Yap, G. P. A.; Ong, T.-G. Org. Lett. 2012, 14,
2046.
In summary, we have developed the Ir-catalyzed
asymmetric alkylation of N-sulfonylbenzamides with
vinyl ethers via C–H bond activation. The asymmetric
reaction with high enantioselectivity was achieved by
use of the hydroxoiridium/chiral diene catalyst.
1
2
3
4
(5)
(a) Pan, S.; Ryu, N.; Shibata, T. J. Am. Chem. Soc. 2012,
134, 17474. (b) Crisenza, G. E. M.; McCreanor, N. G.; Bower, J. F. J.
Am. Chem. Soc. 2014, 136, 10258. (c) Crisenza, G. E. M.; Sokolova,
O. O.; Bower, J. F. Angew. Chem., Int. Ed. 2015, 54, 14866.
5
(6)
For reviews, see: (a) Zheng, C.; You, S.-L. RSC Adv. 2014,
6
7
8
9
ASSOCIATED CONTENT
4, 6173. (b) Wencel-Delord, J.; Colobert, F. Chem.–Eur. J. 2013, 19,
14010. (c) Giri, R.; Shi, B.-F.; Engle, K. M.; Maugel, N; Yu, J.-Q.
Chem. Soc. Rev. 2009, 38, 3242. For examples of the asymmetric
intermolecular hydroarylation reactions, see: Ir; (d) Aufdenblatten, R.;
Diezi, S.; Togni, A. Monatsh. Chem. 2000, 131, 1345. (e) Dorta, R.;
Togni, A. Chem. Commun. 2003, 760. (f) Sevov, C. S.; Hartwig, J. F.
J. Am. Chem. Soc. 2013, 135, 2116. (g) Shirai, T.; Yamamoto, Y.
Angew. Chem., Int. Ed. 2015, 54, 9894. Rh; (h) Ye, B.; Cramer, N. J.
Am. Chem. Soc. 2013, 135, 636. Co; (i) Lee, P.-S.; Yoshikai, N. Org.
Lett. 2015, 17, 22. Sc; (j) Song, G.; O, W. W. N.; Hou, Z. J. Am.
Chem. Soc. 2014, 136, 12209. For examples of enantioselective hy-
droarylation using prochiral arenes, see (k) Kakiuchi, F.; Gendre, P.
L.; Yamada, A.; Ohtaki, H.; Murai, S. Tetrahedron: Asymmetry 2000,
11, 2647. (l) Shibata, T.; Shizuno, T. Angew. Chem., Int. Ed. 2014, 53,
5410.
Supporting Information. Experimental procedures and
compound characterization data. This material is available
free of charge via the Internet at http://pubs.acs.org.
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
AUTHOR INFORMATION
Corresponding Author
tnishi@kuchem.kyoto-u.ac.jp
ACKNOWLEDGMENT
This work was supported by JSPS KAKENHI Grant Num-
ber 15H03810. Y.E. thanks the JSPS for a research Fel-
lowship for Young Scientists. We thank Prof. A. Osuka
(Kyoto University) for X-ray crystallographic analysis.
(7)
For examples of asymmetric intramolecular hydroarylation
and hydroalkenylation reactions, see: (a) Fujii, N.; Kakiuchi, F.;
Yamada, A.; Chatani, N.; Murai, S. Chem. Lett. 1997, 425. (b) Thalji,
R. K.; Ellman, J. A.; Bergman, R. G. J. Am. Chem. Soc. 2004, 126,
7192. (c) Wilson, R. M.; Thalji, R. K.; Bergman, R. G.; Ellman, J. A.
Org. Lett. 2006, 8, 1745. (d) Harada, H.; Thalji, R. K.; Bergman, R.
G.; Ellman, J. A. J. Org. Chem. 2008, 73, 6772. (e) Tsai, A. S.; Wil-
son, R. M.; Harada, H.; Bergman, R. G.; Ellman, J. A. Chem. Com-
mun. 2009, 3910. (f) Ye, B.; Donets, P. A.; Cramer, N. Angew. Chem.,
Int. Ed. 2014, 53, 507. (g) Liu, C.; Widenhoefer, R. A. Org. Lett.
2007, 9, 1935.
REFERENCES
(1)
For pioneering studies, see: (a) Lewis, L. N.; Smith, J. F. J.
Am. Chem. Soc. 1986, 108, 2728. (b) Murai, S.; Kakiuchi, F.; Sekine,
S.; Tanaka, Y.; Kamatani, A.; Sonoda, M.; Chatani, N. Nature 1993,
366, 529. (c) Kakiuchi, F.; Murai, S. Acc. Chem. Res. 2002, 35, 826.
For recent reviews, see: (d) Colby, D. A.; Bergman, R. G.; Ellman, J.
A. Chem. Rev. 2010, 110, 624. (e) Sun, C.-L.; Li, B.-J.; Shi, Z.-J.
Chem. Commun. 2010, 46, 677. (f) Lyons, T. W.; Sanford, M. S.
Chem. Rev. 2010, 110, 1147. (g) Ackermann, L. Chem. Rev. 2011,
111, 1315. (h) Kuhl, N.; Hopkinson, M. N.; Wencel-Delord, J.; Glori-
ous, F. Angew. Chem., Int. Ed. 2012, 51, 10236. (i) Colby, D. A.; Tsai,
A. S.; Bergman, R. G.; Ellman, J. A. Acc. Chem. Res. 2012, 45, 814.
(j) Rouquet, G.; Chatani, N. Angew. Chem., Int. Ed. 2013, 52, 11726.
(k) Zheng, Q.-Z.; Jiao, N. Tetrahedron Lett. 2014, 55, 1121. (l) Yo-
shikai, N. Bull. Chem. Soc. Jpn. 2014, 87, 843.
(8)
(9)
Ebe, Y.; Nishimura, T. J. Am. Chem. Soc. 2015, 137, 5899.
For an example of Rh-catalyzed regioselective hydroaryla-
tion of dihydrofurans, see: Shibata, K.; Chatani, N. Chem. Sci. 2016, 7,
240.
(10) For examples of N-sulfonyl amides as directing groups,
see: (a) Zhu, C.; Falck, J. R. Org. Lett. 2011, 13, 1214. (b) Péron, F.;
Fossey, C.; Cailly, T.; Fabis, F. Org. Lett. 2012, 14, 1827. (c) Zhu,
C.; Falck, J. R. Chem. Commun. 2012, 48, 1674 (d) Xia, X.-F.; Wang,
Y.-Q.; Zhang, L.-L.; Song, X. R.; Liu, X.-Y.; Liang, Y.-M. Chem.–
Eur. J. 2014, 20, 5087. For examples of Cp*Ir(III)-catalyzed C–H
amination of aromatic amides, see: (e) Kim, H.; Shin, K.; Chang, S. J.
Am. Chem. Soc. 2014, 136, 5904. (f) Kim, H.; Chang, S. ACS Catal.
2015, 5, 6665.
(11) For an annulation reaction via an amidoiridium, see: Hata-
no, M.; Nishimura, T. Angew. Chem., Int. Ed. 2015, 54, 10949.
(12) Although the reaction was promoted by use of [IrCl(cod)]2
in the presence of bases, the hydroxoiridium complex without adding
any bases displayed the highest catalytic activity, see the Supporting
Information (Table S1).
(13) For reviews, see: (a) Defieber, C.; Grützmacher, H.; Car-
reira, E. M. Angew. Chem., Int. Ed. 2008, 47, 4482. (b) Shintani, R.;
Hayashi, T. Aldrichimica Acta 2009, 42, 31. (c) Feng, C.-G.; Xu, M.-
H.; Lin, G.-Q. Synlett 2011, 1345.
(14) Nishimura, T.; Kumamoto, H.; Nagaosa, M.; Hayashi, T.
Chem. Commun. 2009, 5713. For recent examples, see: (b) Nishimura,
T.; Yasuhara, Y.; Sawano, T.; Hayashi, T. J. Am. Chem. Soc. 2010,
132, 7872. (c) Nishimura, T.; Nagamoto, M.; Ebe, Y.; Hayashi, T.
Chem. Sci. 2013, 4, 4499. (d) Ebe, Y.; Nishimura, T. J. Am. Chem.
Soc. 2014, 136, 9284.
(2)
For selected examples, see: (a) Kakiuchi, F.; Sekine, S.;
Tanaka, Y.; Kamatani, A.; Sonoda, M.; Chatani, N.; Murai, S. Bull.
Chem. Soc. Jpn. 1995, 68, 62. (b) Lim, Y.-G.; Kang, J.-B. Kim, Y. H.
J. Chem. Soc., Perkin Trans. 1 1996, 2201. (c) Lenges, C. P.;
Brookhart, M. J. Am. Chem. Soc. 1999, 121, 6616. (d) Matsumoto, T.;
Periana, R. A.; Taube, D. J.; Yoshida, H. J. Mol. Catal. A. Chem.
2002, 180, 1. (e) Jun, C.-H.; Moon, C. W.; Hong, J.-B.; Lim, S.-G.;
Chung, K.-Y.; Kim, Y.-H. Chem.–Eur. J. 2002, 8, 485. (f) Tan, K.
L.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2002, 124,
13964. (g) Tsuchikama, K.; Kasagawa, M.; Hashimoto, Y.; Endo, K.;
Shibata, T. J. Organomet. Chem. 2008, 693, 3939. (h) Zhang, Y. J.;
Skucas, E.; Krische, M. J. Org. Lett. 2009, 11, 4248. (i) Martinez, R.;
Simon, M.-O.; Chevalier, R.; Pautigny, C.; Genet, J.-P.; Darses, S. J.
Am. Chem. Soc. 2009, 131, 7887. (j) Ilies, L.; Chen, Q.; Zeng, X.;
Nakamura, E. J. Am. Chem. Soc. 2011, 133, 5221. (k) Takebayashi,
S.; Shibata, T. Organometallics 2012, 31, 4114. (l) Schinkel, M.;
Marek, I.; Ackermann, L. Angew. Chem., Int. Ed. 2013, 52, 3977.
(m) Xu, W.; Yoshikai, N. Angew. Chem., Int. Ed. 2014, 53, 14166.
(3)
For a review see, Crisenza, G. E. M.; Bower, J. F. Chem.
Lett. 2016, 45, 2.
(4)
(a) Uchimaru, Y. Chem. Commun. 1999, 1133. (b) Gao, K.;
(15) No reaction was also observed for 2-phenylpyridine.
(16) The absolute configurations of 3ai and 3aj were deter-
mined by X-ray crystallographic analysis. For others, they were as-
signed by analogy with 3ai and 3aj.
(17) For an example of DFT calculations, see: Zhang, M.;
Huang, G. Dalton Trans. 2016, 45, 3552.
Yoshikai, N. J. Am. Chem. Soc. 2011, 133, 400. (c) Lee, P.-S.; Yoshi-
kai, N. Angew. Chem., Int. Ed. 2013, 52, 1240. (d) Dong, J.; Lee, P.-
S.; Yoshikai, N. Chem. Lett. 2013, 42, 1140. For examples of non-
directed alkene hydroheteroarylation: (e) Mukai, T.; Hirano, K.; Satoh,
T.; Miura. M. J. Org. Chem. 2009, 74, 6410. (f) Nakao, Y.; Kashihara,
N.; Kanyiva, K. S.; Hiyama, T. Angew. Chem., Int. Ed. 2010, 49,
4451. (g) Nakao, Y.; Yamada, Y.; Kashihara, N.; Hiyama, T. J. Am.
ACS Paragon Plus Environment

Page 5 of 5
Journal of the American Chemical Society
1
2
3
4
5
O
O
R
Ms
R
[Ir(OH)((S,S )-Me-tfb*)]2
Ms
N
N
H
H
+
toluene, 70 °C
OR'
H
6
83–98% ee
OR'
7
8
9
– H2O
F
F
O
O
F
Ms
Ms
N
N
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
F
Ir
Ir
H
amidoiridium(I)
Me
(S,S )-Me-tfb*
H
Me
5
ACS Paragon Plus Environment