α-C-H Alkylation of Methyl Sulfides with Alkenes by a Scandium Catalyst

Article abstract of DOI:10.1021/jacs.7b11245

The C - H addition of sulfides to alkenes is an atom-efficient route for the functionalization and modification of sulfide compounds through C - C bond formation, but this transformation is highly challenging. We report here the regioselective α-C(sp³) - H addition of a wide range of methyl sulfides to a variety of olefins and dienes by a half-sandwich scandium catalyst. This protocol provides a unique route for the synthesis of diverse sulfide derivatives through C - C bond formation at a sulfur-adjacent carbon atom in a 100% atom efficient fashion.

Full text of DOI:10.1021/jacs.7b11245

Subscriber access provided by University of Florida | Smathers Libraries
Communication
#-C-H Alkylation of Methyl Sulfides with Alkenes by a Scandium Catalyst
Yong Luo, Yuanhong Ma, and Zhaomin Hou
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b11245 • Publication Date (Web): 20 Dec 2017
Downloaded from http://pubs.acs.org on December 20, 2017
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
α-C−H Alkylation of Methyl Sulfides with Alkenes by a Scan-
dium Catalyst
†
†
,†,‡
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Yong Luo, Yuanhong Ma, and Zhaomin Hou*
†
Organometallic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
‡
Advanced Catalysis Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama
3
51-0198, Japan
Supporting Information Placeholder
ABSTRACT: The C−H addition of sulfides to alkenes is an
atom-efficient route for the functionalization and modifica-
tion of sulfide compounds through C−C bond formation,
but this transformation is highly challenging. We report
We have recently found that the interaction between a
heteroatom (such as oxygen, nitrogen, and sulfur) and a rare
earth metal can effectively enhance various rare-earth-
8,9
catalyzed transformations, such as the regioselective meth-
3
9a
here the regioselective α-C(sp )−H addition of a wide range
ylalumination of alkenes and alkynes, ortho-selective aro-
9b,c,e
of methyl sulfides to a variety of olefins and dienes by a
half-sandwich scandium catalyst. This protocol provides a
unique route for the synthesis of diverse sulfide derivatives
through C−C bond formation at a sulfur-adjacent carbon
atom in a 100% atom efficient fashion.
matic C−H addition to alkenes,
and the syndiospecific
9h
polymerization of α-olefins. These findings invoked our
interest in the catalytic C−H addition of sulfides to alkenes
by rare earth catalysts. We report here the unprecedented
hydrothiomethylation of a variety of olefins and dienes with
a wide range of methyl sulfides by a half-sandwich scandium
catalyst. This work represents the first example of regioselec-
3
tive catalytic α-C(sp )−H addition of sulfides to unactivated
Sulfide motifs are important components in a large number
of natural products, bioactive molecules, functional materials,
alkenes, efficiently affording diverse sulfide derivatives
through C−C bond formation at a sulfur-adjacent carbon
atom (Scheme 1c).
1
and organocatalysts. Therefore, the development of efficient
and selective routes for the functionalization of sulfides is of
great interest and importance. Among possible approaches,
the C−H addition of a sulfide compound to alkenes is the
most atom-efficient route for the synthesis of alkylated sul-
Scheme 1. α-C−H Functionalization of Sulfides with
Alkenes
2
fide derivatives. However, this transformation is highly chal-
lenging and has met with only limited success to date, partly
because a sulfide unit often acts as a poison to transition
3
metal catalysts and can also easily undergo C−S bond cleav-
4
age in the presence of a transition metal catalyst. There are a
number of reports of the use of MeS as a directing group for
5
transition metal-catalyzed C−H activation. The α-C−H func-
tionalization of some sulfides by cross-dehydrogenative cou-
6
pling (CDC) has also been reported. Regarding the C−H
7
addition of sulfides to alkenes, the reaction of tetrahy-
drothiophene with fluorinated alkenes in the presence of a
peroxide was reported to give the corresponding α-C−H al-
kylation product via a radical-initiated mechanism (Scheme
7
a
1
a). Under the coexistence of a copper compound and a
At first, we screened a series of rare earth catalysts bearing
different ligands for the reaction of n-pentyl methyl sulfide
peroxide, the reaction of sulfides with some activated alkenes
7d
yielded the alkenylated products (Scheme 1b). In all of the-
se reactions, only alkenes having an electron-withdrawing
group showed reactivity, and symmetrically substituted sul-
fides were usually used as a reaction partner to avoid regiose-
(
1a) with 1-octene (2a) in toluene at 70 °C (Table 1). A com-
bination of the scandium tris(o-N,N-dimethylaminobenzyl)
complex Sc-1 with one equiv. of [Ph C][B(C F ) ] yielded a
3
6 5 4
3
trace amount of the hydrothiomethylation product 3a in 48 h
(Table 1, entry 1). The C H -ligated scandium bis(o-N,N-
lectivity problems. The regioselective catalytic α-C(sp )−H
addition of a sulfide compound bearing two different hydro-
carbon substituents to an unactivated alkene has not been
reported previously (See Scheme 1c).
5
5
dimethylaminobenzyl) complex Sc-2 was inactive under the
same conditions (Table 1, entry 2). In contrast, the C Me -
5
5
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 5
ligated analog Sc-3 afforded the desired hydrothiomethyla-
the corresponding intermolecular hydrothiomethylation
product 3h in 81% isolated yield, while the MeS group bond-
ed to the phenyl group in 2h remained intact. This strongly
supports a reaction mechanism involving sulfur coordination,
as the coordination ability of an aryl thioether is weaker than
that of an alkyl thioether. Trimethylsilyl (3i), siloxy (3j), and
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
tion product 3a in 88% yield (Table 1, entry 3). The analogous
rare earth complexes of larger metals such as Y-3, Gd-3 and
Sm-3 were much less effective (Table 1, entries 4-6). These
results suggest that the catalyst activity is significantly influ-
enced by the supporting Cp ligands as well as the rare earth
1
0
12
metals. The C Me SiMe -ligated scandium complex Sc-4
amino (3k) groups were also compatible. The reaction of 1a
5
4
3
showed similar activity (86% yield, Table 1, entry 7) as that of
Sc-3. The THF-bonded scandium trimethylsilylmethyl analog
Sc-5 gave a slightly lower yield (63% yield, Table 1, entry 8),
probably due to the influence of the THF Lewis base ligand
that could hamper the access of the sulfide 1a or the alkene
with norbornene gave the desired hydrothiomethylation
product 3l in 85% yield with excellent diastereoselectivity.
An acyclic internal alkene such as cis-2-octene did not un-
dergo the hydrothiomethylation reaction under the same
conditions probably due to steric hindrance. In the case of
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
1
13
2a to the metal center. Either the neutral scandium complex
styrene, the polymerization of styrene was observed.
Sc-3 or [Ph C][B(C F ) ] alone showed no catalytic activity
3
6 5 4
(Table 1, entry 9 and 10), suggesting that a cationic half-
sandwich scandium alkyl species is essential in this reaction.
When Sc-3a/[Ph C][B(C F ) ] was used as a catalyst, a shorter
Table 2. Hydrothiomethylation of various olefins
a
with pentyl methyl sulfide by Sc-3
3
6 5 4
reaction time (24 h) or lower temperature (50 °C) led to a
lower yield of 3a (81% and 69%, respectively). The reaction at
9
0 °C did not give a higher yield (87%).
Table 1. Catalyst screening for hydrothiomethylation
a
of 1-octene with pentyl methyl sulfide
Entry
[Ln]
Sc-1
Sc-2
Sc-3
Y-3
[B]
Yield (%)
< 5
1
[Ph C][B(C F ) ]
[Ph C][B(C F ) ]
3
6 5 4
2
3
4
5
6
7
8
9
< 5
3
6 5 4
[Ph C][B(C F ) ]
88
3
6 5 4
[Ph C][B(C F ) ]
< 5
3
6 5 4
Gd-3
Sm-3
Sc-4
Sc-5
Sc-3
--
[Ph C][B(C F ) ]
10
3
6 5 4
[Ph C][B(C F ) ]
< 5
3
6 5 4
[Ph C][B(C F ) ]
86
3
6 5 4
a
Reaction conditions: 1a (0.4 mmol), 2 (0.6 mmol, 1.5 equiv.),
[Ph C][B(C F ) ]
63
3
6 5 4
Sc-3 (5 mol%), [Ph C][B(C F ) ] (5 mol%), toluene (2.0 mL),
--
[Ph C][B(C F ) ]
n.r.
n.r.
3
6 5 4
b
70 °C, 48 h, isolated yield, unless otherwise noted. 1a (0.6
mmol), 2 (0.4 mmol). Sc-3 (10 mol%), [Ph C][B(C F ) ] (10
mol%). 1a (0.8 mmol), 2 (0.4 mmol). >20:1 dr
10
3
6 5 4
c
3
6 5 4
a
d
e
Reaction conditions: 1a (0.4 mmol), 2a (0.6 mmol, 1.5 equiv.),
[
7
Ph C][B(C F ) ] (5 mol%), [Ln] (5 mol%), toluene (2.0 mL),
0 C, 48 h, isolated yield.
3
6 5 4
°
Scheme 2. Hydrothiomethylation of dienes with pen-
a
tyl methyl sulfide
H
2m
S
C5H11
C5H11
C5H11
Sc-3
3m 86%
2
n
S
n-C5H11 SCH3
H
H
Sc-3
We then examined the reaction of pentyl methyl sulfide
1a
3n 69%b
(
(
1a) with various olefins (2) under the optimized conditions
Table 2). Olefins containing either aliphatic or aromatic
S
2o
substituents all reacted with 1a in the presence of 5 mol % of
Sc-3 and [Ph C][B(C F ) ], exclusively affording the corre-
Sc-3
3
o 54%b,c
3
6 5 4
sponding branched hydrothiomethylation products (such as
a
Reaction conditions: 1a (0.4 mmol), 2 (0.6 mmol, 1.5 equiv.),
Sc-3 (5 mol%), [Ph C][B(C F ) ] (5 mol%), toluene (2.0 mL),
3a-3e) in moderate to high yields. Aromatic C−Br and C−Cl
3
6 5 4
b
bonds were compatible with the catalyst (see 3f and 3g). In
70 °C, 48 h, isolated yield. Sc-3 (10 mol%), [Ph C][B(C F ) ]
(10 mol%). 1.7 : 1 dr.
3
6 5 4
the case of p-MeSC H CH CH CH=CH (2h), the C−H activa-
c
6
5
2
2
2
tion exclusively took place at the methyl group of 1a to give
2
ACS Paragon Plus Environment

Page 3 of 5
Journal of the American Chemical Society
Dienes could also be efficiently hydrothiomethylated with
1a (Scheme 2). The reaction of 1,3-cyclohexadiene (2m) with
1a in the presence of 5 mol % of Sc-3 and [Ph C][B(C F ) ]
tions.
The
mono-alkylation
of
1,4-
1
2
3
4
5
6
7
8
9
bis(methylthiomethyl)cyclohexane that contains two SCH3
groups could be selectively achieved (3y) when an excess
amount of the sulfide was employed. The methyl sulfides
having a sterically demanding secondary alkyl (3z) or cy-
clooctyl substituent (3aa) directly bonded to the sulfur atom
did not hamper the reaction at the SMe group. The selective
formation of 3ab (81% yield) in the reaction of 2a with 3-
methylthiocholestane further demonstrated the useful po-
tential of this protocol in the alkylation of a methyl sulfide
having a complex substituent. The α-methylene C−H alkyla-
tion of tetrahydrothiophene with 2a could also achieved al-
beit with a higher catalyst loading (10 mol %) (3ac). An acy-
clic dialkyl sulfide such as n-Butyl ethyl sulfide did not un-
dergo C−H alkylation under the same conditions probably
due to steric hindrance.
3
6 5 4
yielded the corresponding thiomethylated cyclohexene
product 3m through C−H addition to the 1,3-diene unit in a
1
4
1
,4-fashion. More remarkably, in the case of unconjugated
1,5-dienes such as 2n and 2o, the hydrothiomethylation was
accompanied by cyclization through sequential insertion of
the two C=C bonds, which afforded the corresponding thi-
omethyl-functionalized cyclopentane derivatives 3n and 3o,
respectively.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Table 3. Hydrothiomethylation of 1-octene with vari-
a
ous alkyl methyl sulfides
H
Sc-3
[
Ph3C][B(C6F5)4]
S
R
SCH3 + C H
6
13
R
C6H13
toluene, 70 oC, 48 h
It is also worth noting that in the reaction of methyl phe-
1
2a
3
3
H
H
H
S
nyl sulfide with 2a, the sp methyl C−H bond, rather than the
Et
2
sp ortho-C−H bond of the phenyl group, was selectively
S
S
C6H13
C6H13
C4H9
C6H13
C6H13
C6H13
C H
3
2
alkylated to give 3ad. This is in sharp contrast with what was
observed previously in the scandium-catalyzed reaction of
anisole with alkenes, in which the reaction exclusively oc-
3
p 95%b
3q
88%b
H
3r 89%
H
H
Ph
2
9c
S
2
Ph
S
S
curred at the sp ortho-C−H bond of the phenyl group. Alt-
hough the reactivity of methyl phenyl sulfide toward 1-octene
(2a) was lower than that of a methyl alkyl sulfide probably
because of the electron-withdrawing influence of the phenyl
group, the reaction of a methyl phenyl sulfide with nor-
bornene (which is more reactive than 1-octene) efficiently
took place, affording the corresponding thiomethyl-
functionalized norbornane derivative (such as 3af) in high
yield.
C6H13
Ph
3
2
3
s 90%
3t 92%
3u 90%
H
H
Br
H
S
5
TMS
S
4
S
C6H13
6 13
C6H13
3
Et
3v 78%
3w 80%
3x 93%
H
H
H
S
S
C6H13
C6H13
MeSH2C
S
C6H13
C5H11
3
y 56%c
3
z 79%b
3aa 84%
Scheme 3. Kinetic isotope effect experiments
H3C
H3C
H
H
CH3
H3C
H
H
H3C
H
S
6 13
C H
H
H
H
S
3ab 81%d
3ac 51%d,e
C6H13
Ph
H
H
H
S
S
C6H13
S
C6H13
ad 42%
3af 86%f
3
3ae 40%
a
Reaction conditions: 1 (0.4 mmol), 2a (0.6 mmol), Sc-3 (5
mol%), [Ph C][B(C F ) ] (5 mol%), toluene (2.0 mL), 70 °C,
3
6 5 4
b
c
48 h, isolated yield, unless otherwise noted. 1:1 dr. 1 (0.8
mmol), 2a (0.4 mmol). 1.3:1 dr. Sc-3 (10 mol%),
[Ph C][B(C F ) ] (10 mol%). Norbornene (0.6 mmol) was
d
e
To gain information on the reaction mechanism, a 1:1 mix-
ture of the sulfide 1q and the methyl-deuterated sulfide 1q-d
was used to react with 1-octene under the standard reaction
f
3
6 5 4
used instead of 1-octene, and >20:1 dr.
1
conditions (Scheme 3a). The H NMR analysis of the product
Table 3 summarizes the reactions of 1-octene (2a) with var-
ious alkyl (or phenyl) methyl sulfides (1). The alkyl methyl
sulfides containing either acyclic or cyclic aliphatic groups or
aromatic groups could be smoothly incorporated into the
alkene substrate to give the corresponding hydrothiomethyl-
ation products (such as 3p-3v) in high yields. The reaction
exclusively occurred at the methyl group of the sulfides,
while the methylene unit remained intact, probably due to
steric influence. An internal alkene moiety (3w) and the
at the stage of 15% yield revealed a significant kinetic isotope
effect (KIE = 4.9). No H/D exchange was observed between
1q and 1q-d. The relative ratio of the initial rates of the two
side-by-side reactions using 1q and 1q-d, respectively, was
determined to be 5.5 (Schemes 3b and 3c). These results sug-
gest that the C−H activation of the methyl group in the sul-
fides is involved in the rate-determining step.
A possible reaction mechanism is depicted in Scheme 4.
Similar to the hydroaminoalkylation of alkenes with tertiary
SiMe group (3x) in the sulfides survived the reaction condi-
3
3
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 5
9
f
amines reported previously, the coordination of the sulfur
atom of a methyl sulfide 1 to the Sc atom in the cationic half-
sandwich scandium aminobenzyl species A, which was gen-
ACKNOWLEDGMENT
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
This work was supported by a Grant-in-Aid for Scientific
Research (S) (No. 26220802) from JSPS. We thank Mrs. Akiko
Karube and Dr. Takemichi Nakamura for high resolution
mass spectrometry (HRMS) analysis.
1
5
erated by the reaction of Sc-3 with [Ph C][B(C F ) ], fol-
3
6 5 4
lowed by C−H activation (deprotonation) of the methyl
group in 1 by the benzyl species could give a three-
membered metallacycle intermediate like B with release of
N,N-dimethyl-o-toluidine. This step was supported by obser-
vation of the formation of CH DC H NMe -o in the reaction
of CD SCH CH(Et)( C H ) with 2a catalyzed by Sc-
/[Ph C][B(C F ) ] (see Supporting Information). The inser-
tion of an alkene 2 into the C−Sc bond in B would give C,
which on hydrogen abstraction of the methyl group in 1 should
release the final product 3 and regenerate the active species
B.
REFERENCES
2
6
4
3
(1) (a) Poirier, D.; Auger, S.; Mérand, Y.; Simard, J.; Labrie, F. J. Med.
Chem. 1994, 37, 1115. (b) Greger, H.; Pacher, T.; Vajrodaya, S.; Bacher,
M.; Hofer, O. J. Nat. Prod. 2000, 63, 616. (c) Ke, Z.; Tan, C. K.; Chen,
F.; Yeung, Y.-Y. J. Am. Chem. Soc. 2014, 136, 5627. (d) Nakano, M.;
Takimiya, K. Chem. Mater. 2017, 29, 256.
n
3
2
4
9
3
3 6 5 4
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
2) For a recent review on catalytic C−H addition to alkenes, see:
Dong, Z.; Ren, Z.; Thompson, S. J.; Xu, Y.; Dong, G. Chem. Rev. 2017,
17, 9333.
1
(3) Hegedus, L. L.; McCabe, R. W. Catalyst Poisoning; Marcel Dekker:
New York, 1984.
(4) Recent reviews: (a) Wang, L.; He, W.; Yu, Z. Chem. Soc. Rev. 2013,
Scheme 4. Proposed reaction mechanism. The coun-
ter anion in A, B and C is omitted for clarity.
4
2, 599. (b) Modha, S. G.; Mehta, V. P.; Van der Eycken, E. V. Chem.
Soc. Rev. 2013, 42, 5042.
(5) For examples, see: (a) Shabashov, D.; Daugulis, O. J. Am. Chem.
Soc. 2010, 132, 3965. (b) Yu, M.; Xie, Y.; Xie, C.; Zhang, Y. Org. Lett.
Sc
N
[Ph C][B(C F ) ]
Sc
N
+
3
6
5
4
N
2012, 14, 2164. (c) Yao, J.; Yu, M.; Zhang, Y. Adv. Synth. Catal. 2012,
Sc-3
A
3
54, 3205. (d) Zhang, X.-S.; Zhu, Q.-L.; Zhang, Y.-F.; Li, Y.-B.; Shi, Z.-J.
S
H
R1
S
H
Chem. Eur. J. 2013, 19, 11898. (e) Zhang, X.-S.; Zhang, Y.-F.; Li, Z.-W.;
Luo, F.-X.; Shi, Z.-J. Angew. Chem., Int. Ed. 2015, 54, 5478. (f) Li, H.-L.;
Kuninobu, Y.; Kanai, M. Angew. Chem., Int. Ed. 2017, 56, 1495. (g) Li,
H.-L.; Kanai, M.; Kuninobu, Y. Org. Lett. 2017, 19, 5944.
(6) (a) Li, Z.; Yu, R.; Li, H. Angew. Chem., Int. Ed. 2008, 47, 7497. (b)
Li, Z.; Li, H.; Guo, X.; Cao, L.; Yu, R.; Li, H.; Pan, S. Org. Lett. 2008, 10,
803. (c) Wu, Z.; Pi, C.; Cui, X.; Bai, J.; Wu, Y. Adv. Synth. Catal. 2013,
355, 1971. (d) Sun, K.; Wang, X.; Li, G.; Zhu, Z.; Jiang, Y.; Xiao, B.
Chem. Commun. 2014, 50, 12880. (e) Kawade, R. K.; Huple, D. B.; Lin,
R.-J.; Liu, R.-S. Chem. Commun. 2015, 51, 6625. (f) Guo, S.-R.; Kumar,
P. S.; Yuan, Y.-Q.; Yang, M.-H. Eur. J. Org. Chem. 2016, 4260. (g) Li,
Q.; Hu, W.; Hu, R.; Lu, H.; Li, G. Org. Lett. 2017, 19, 4676.
(7) (a) Chen, J.; Kirchmeier, R. L.; Shreeve, J. M. Inorg. Chem. 1996,
35, 6676. (b) Wei, W.-T.; Zhou, M.-B.; Fan, J.-H.; Liu, W.; Song, R.-J.;
Liu, Y.; Hu, M.; Xie, P.; Li, J.-H. Angew. Chem., Int. Ed. 2013, 52, 3638.
(c) Yang, H.; Yan, H.; Sun, P.; Zhu, Y.; Lu, L.; Liu, D.; Rong, G.; Mao, J.
Green Chem. 2013, 15, 976. (d) Cao, H.; Liu, D.; Liu, C.; Hu, X.; Lei, A.
Org. Biomol. Chem. 2015, 13, 2264. (e) Kamijo, S.; Takao, G.; Kamijo,
K.; Tsuno, T.; Ishiguro, K.; Murafuji, T. Org. Lett. 2016, 18, 4912. (f)
Kamijo, S.; Kamijo, K.; Maruoka, K.; Murafuji, T. Org. Lett. 2016, 18,
R1
N
1
1
H
H
S
R1
R2
R1
3
S
Sc
R1
Sc
S
C
B
R2
R2
2
In summary, we have achieved for the first time the hy-
drothiomethylation of a variety of olefins and dienes with a
series of methyl sulfides by using a half-sandwich scandium
catalyst such as Sc-3. This protocol offers an atom-efficient
route for the modification and functionalization of sulfides
through the regiospecific α-C−H addition to a C=C double
bond, leading to formation of a new family of sulfide deriva-
tives with diversified substituents. The success of this trans-
formation is obviously due to the unique affinity and reactiv-
ity of cationic scandium alkyl species towards a sulfide group
and C–H and C=C bonds. We expect these unique features
could also be applied to other related transformations. Stud-
ies along this line are currently in progress.
6
1
(
516. (g) Xia, D.; Li, Y.; Miao, T.; Li, P.; Wang, L. Green Chem. 2017, 19,
732.
8) A recent review: Nishiura, M.; Guo, F.; Hou, Z. Acc. Chem. Res.
2015, 48, 2209.
(9) Selected examples: (a) Takimoto, M.; Usami, S.; Hou, Z. J. Am.
Chem. Soc. 2009, 131, 18266. (b) Guan, B.-T.; Hou, Z. J. Am. Chem. Soc.
2011, 133, 18086. (c) Oyamada, J.; Hou, Z. Angew. Chem., Int. Ed. 2012,
51, 12828. (d) Guan, B.-T.; Wang, B.; Nishiura, M.; Hou, Z. Angew.
ASSOCIATED CONTENT
Supporting Information
Chem., Int. Ed. 2013, 52, 4418. (e) Song, G.; Luo, G.; Oyamada, J.; Luo,
Y.; Hou, Z. Chem. Sci. 2016, 7, 5265. (f) Nako, A. E.; Oyamada, J.;
Nishiura, M.; Hou, Z. Chem. Sci. 2016, 7, 6429. (g) Liu, F.; Luo, G.;
Hou, Z.; Luo, Y. Organometallics 2017, 36, 1557. (h) Wang, C.; Luo, G.;
Nishiura, M.; Song, G.; Yamamoto, A.; Luo, Y.; Hou, Z. Sci. Adv. 2017,
Synthetic procedures, characterization data for all new com-
pounds. This material is available free of charge via the In-
ternet at http://pubs.acs.org.
3
, e170101.
(10) Similar metal and ligand influences were also observed in rare-
earth-catalyzed olefin polymerization (see: ref. 8). This is probably
due to the stability (or lifetime) of the resulting cationic half-
sandwich rare earth metal monoalkyl active species.
(11) Addition of THF to the THF-free Sc complex Sc-4 deactivated the
catalyst. The similar THF influence on olefin polymerization was also
observed previously. See: Li, X.; Nishiura, M.; Hu, L.; Mori, K.; Hou,
Z. J. Am. Chem. Soc. 2009, 131, 13870.
AUTHOR INFORMATION
Corresponding Author
houz@riken.jp
Notes
The authors declare no competing financial interest.
4
ACS Paragon Plus Environment

Page 5 of 5
Journal of the American Chemical Society
(
12) The use of an excess amount of the sulfide 1a was needed to
1
2
3
4
5
6
7
8
9
achieve a significant yield of the desired products (3j,k) in the case
of alkenes containing a siloxy or amino group, because the coordina-
tion of the siloxy or amino group could compete with that of the
sulfide unit.
(
13) For the scandium-catalyzed polymerization of styrene, see: Luo,
Y.; Baldamus, J.; Hou, Z. J. Am. Chem. Soc. 2004, 126, 13910.
14) For the 1,4-polymerization of 1,3-cyclohexadiene by a similar
scandium catalyst, see: Li, X.; Hou, Z. Macromolecules 2010, 43, 8904.
15) Li, X.; Nishiura, M.; Mori, K.; Mashiko, T.; Hou, Z. Chem. Com-
mun. 2007, 4137.
(
(
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
5
ACS Paragon Plus Environment