A Synthetic Strategy for 2-Alkylchromanones: Fe(III)-Catalyzed A-Reductive Cross-Coupling of Unactivated Alkenes with Chromones

Article abstract of DOI:10.1055/s-0036-1591601

A new synthetic approach for 2-alkylchromanones utilizing Fe (III)-catalyzed reductive cross-coupling of olefins with chromones has been developed. The reaction conditions are mild, and various substituted alkenes are applicable to the process. Moreover, control experiments were conducted, and a plausible mechanism is proposed.

Full text of DOI:10.1055/s-0036-1591601

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© Georg Thieme Verlag Stuttgart · New York
2018, 29, A–F
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X.-L. Chen et al.
Letter
Synlett
A Synthetic Strategy for 2-Alkylchromanones: Fe(III)-Catalyzed
Reductive Cross-Coupling of Unactivated Alkenes with Chromones
Xu-Ling Chena,b
Yu Donga,b
Lei Tangc
Xiao-Mei Zhanga
Ji-Yu Wang*a
O
O
R1
Fe(acac)3/PhSiH3
EtOH, 40 °C
R3
R3
+
R2
R
R
O
R4
O
R4
R1 R2
⋅ reductive coupling of olefins
⋅ mild conditions
⋅ 24 examples, up to 85% yield
⋅ alkenes: monosubstituted or disubstituted terminal alkenes,
trisubstituted and tetrasubstituted alkenes
⋅ R: Me, MeO, OH, F, Cl, Br
a Chengdu Institute of Organic Chemistry, Chinese Academy
of Sciences, Chengdu 610041, P. R. of China
Jiyuwang@cioc.ac.cn
b University of Chinese Academy of Sciences, Beijing 100049,
P. R. of China
c Laboratory of Anaesthesia & Critical Care Medicine, Transla-
tional Neuroscience Center, and Department of Anaesthesi-
ology, West China Hospital, Sichuan University, Chengdu
610041, P. R. of China
Received: 30.04.2018
Accepted after revision: 08.06.2018
Published online: 10.07.2018
synthesis of sulfone adducts. Also, this reactivity was ex-
tended to an olefin-based Minisci reaction to functionalize
heterocyclic scaffolds.4 Although a variety of acceptor ole-
fins were presented in these studies, the behavior of the
chromone ring system towards olefin reductive coupling
conditions has not been reported yet.
DOI: 10.1055/s-0036-1591601; Art ID: st-2018-b0277-l
Abstract A new synthetic approach for 2-alkylchromanones utilizing
Fe (III)-catalyzed reductive cross-coupling of olefins with chromones
has been developed. The reaction conditions are mild, and various sub-
stituted alkenes are applicable to the process. Moreover, control experi-
ments were conducted, and a plausible mechanism is proposed.
The chromanone structure is widely distributed among
natural products and pharmaceutical molecules. These bio-
logically active compounds exhibit remarkable activities in-
cluding antitumor, antibacterial, antioxidant, and anti-
microbial properties (Figure 1).5 Among the derivatives of
chromanone, 2-alkylchromanone represents an extremely
important type of bioactive compounds.6 Therefore, the de-
velopment of facile syntheses of 2-alkylchromanones has
attracted considerable attention.7 For example, Zimmer-
man et al. developed a conjugate addition methodology us-
ing Zn(OTf)2 as the catalyst and Et3B as the initiator in the
presence of molecular oxygen for the synthesis of 2-alkyl-
chromanones (Scheme 1).8 In 2013, the group of Feringa re-
ported a copper-catalyzed direct conjugate addition of Gri-
gnard reagents to chromones (Scheme 1).9 In 2014, Han’s
group established oxidative C(sp3)−H bond functionaliza-
tion of alkanes and conjugate addition to chromones using
Key words olefin reductive cross-coupling, unactivated olefins, radi-
cal conjugate addition, 2-alkylchromanones
Carbon–carbon (C–C) bonds form the backbone of many
important molecules, including polymers, dyes, and phar-
maceutical agents. The development of new methods to
create these essential connections in a rapid and practical
fashion has been the focus of numerous organic chemists.
Recently, the Fe(III)-catalyzed coupling of unactivated
alkenes has emerged as a powerful and distinct method for
the facile construction of C−C bonds.1 For example, Baran
and co-workers paired unactivated alkenes as radical do-
nors with electron-withdrawing radical acceptors under Fe-
mediated reductive conditions to effect conjugate addition
for building C–C bonds. In addition, they expanded this
methodology to a wide range of heteroatom-substituted
olefin substrates.2 In 2016, Cui’s group reported the Fe-cat-
alyzed hydroalkylation of olefins with p-quinone methides
(p-QMs) for accessing phenols.3 These methods have pro-
vided rapid access to many compounds that were difficult
or perhaps impossible to obtain with previous methods. Re-
cently, vinyl sulfone acceptor olefins were developed by Ba-
ran and co-workers, and this protocol allowed the efficient
OH
O
OH
O
N
O
O
Cl
N
O
O
MeO2C OH
blennolide C
Br
hypolipemic agent
SIRT2 inhibitor
Figure 1 Biological compounds containing the chromanone skeleton
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

B
X.-L. Chen et al.
Letter
Synlett
DTBP (di-tert-butyl peroxide) as the oxidant to synthesize
2-alkylchromanones (Scheme 1).10 More recently,
Mattson’s group reported silanediol-catalyzed addition of
silyl ketene acetals to benzopyrylium triflates generated
from chromenones with silyl triflate for the functionaliza-
tion of chromones (Scheme 1).11 Additionally, the group of
Streuff developed Ti(III)-catalyzed reductive umpolung of
Michael acceptors to synthesize 2-alkylchromanones with
chromones and acrylonitrile.12 Despite these advances, the
development of a mild and general method for the facile
synthesis of 2-alkylchromanones from simple starting ma-
terials remains an important challenge. Inspired by the
studies on reductive cross-coupling,2,3 we first report the
direct cross-coupling of simple unactivated olefins with
chromones under reductive conditions to provide access to
2-alkylchromanones.8–12
Zimmerman: 8
Feringa:9
MgBr
O
O
O
O
O
O
R
R
I
CuBr.SMe2
ligand
Zn(OTf)2
Et3B/O2
R
Han:10
O
O
DTBP
+
H Alkyl
O
O
Alkyl
Mattson:11
O
OSiR3
O
OSiR3
OMe
O
R3SiOTf
*
O
O
OMe
silanediol
catalyst
O
O
OTf
Streuff:12
O
Cp2TiCl2
Mn, Et3N.HCl
We commenced our study by investigating chromone 1a
and unactivated alkene 2f (Table 1). When the reaction was
conducted in the presence of 0.3 equiv of Fe(acac)3 and 2.0
equiv of PhSiH3, the reaction proceeded and afforded the
expected 2-alkylchromanone 3af in 75% yield (entry 1). The
reaction did not take place if Fe2(ox)3·6H2O was employed
as the catalyst (entry 2). The next change of the catalyst to
Co(acac)2 only afforded the product in 12% yield (entry 3).
What’s more, when other reductants such as NaBH4, Et3SiH
were used, no product was observed (entries 4−5). Addi-
tionally, the use of (EtO)3SiH as the reductant led to a lower
+
CN
TMSCl
O
CN
O
This work: reductive cross-coupling
O
O
O
R1
Fe(acac)3/PhSiH3
EtOH
R3
R3
+
R
R2
R
R4
O
R4
R1 R2
Scheme 1 The synthesis of 2-alkylchromanones
Table 1 Optimization Experimentsa
O
O
Fe(acac)3/PhSiH3
+
OH
OH
O
O
1a
2f
3af
Entry
Cat.
(0.3 equiv)
Reductant (equiv)
Solvent
(0.5 M)
T
(°C)
Yield (%)b
1
2
Fe(acac)3
Fe2(ox)3·6H2O
Co(acac)2
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
PhSiH3 (2)
PhSiH3 (2)
PhSiH3 (2)
NaBH4 (2)
Et3SiH (2)
(EtO)3SiH (2)
PhSiH3 (3)
PhSiH3 (3)
PhSiH3 (3)
PhSiH3 (3)
PhSiH3 (3)
PhSiH3 (3)
PhSiH3 (3)
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
60
60
60
60
60
60
60
40
40
40
40
40
40
75
−
3
12
−
4
5
−
6
50
82
83
−
7
8
9
cyclohexane
MeCN
10
11
12
13
37
43
37
60
CH2Cl2
THF
MeOH
a Reaction conditions: 1a (0.3 mmol), 2f (3 equiv), Fe(acac)3 (0.3 equiv), PhSiH3 (3 equiv), EtOH (0.5 M), 40 °C, 5 h.
b Isolated yields.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

C
X.-L. Chen et al.
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Synlett
yield (entry 6). To our delight, when the amount of PhSiH3
was increased to 3.0 equiv, the yield of product could be im-
proved to 82% (entry 7). The product was still formed with
83% yield when the reaction was conducted at 40 °C (entry
8). Additionally, the survey of solvents showed that cyclo-
hexane, MeCN, CH2Cl2, THF, and MeOH were inferior and
gave the product in lower yield (entries 9−13).
Having the optimized conditions in hand, we set out to
explore the scope of unactivated alkenes (Scheme 2). Vari-
ous olefins served as viable donor substrates to achieve the
formation of 2-alkylchromanones. For example, when the
monosubstituted terminal alkene dodec-1-ene was subject-
ed to this process, the reaction proceeded smoothly to give
the corresponding secondary alkylated chromanone 3aa in
65% yield. The reaction with prop-2-en-1-ol successfully
provided product 3ab (dr = 1.1:1) in 62% yield. In addition,
disubstituted terminal alkenes were well applicable in this
transformation providing tertiary alkylated chromanones
in moderate to good yields, with exclusive bond formation
occurring at the most substituted carbon of the olefins
(3ac−3ae). Notably, hydroxyl and piperidine ring function-
alities were well tolerated in this process, thus offering op-
portunities for further derivatization. Moreover, a reaction
with a trisubstituted alkene resulted in 83% yield of product
3af.13 An alkene with a ketone as a functional group was
also tolerated to furnish product 3ag in 82% yield. Particu-
larly, (−)-β-citronellol was amenable to this protocol afford-
ing product 3ah in moderate yield, which might be chal-
lenging to prepare in other ways. A tetrasubstituted olefin
could be used as viable substrate as well (3ai). Next, a range
of cyclic alkenes were tested in this process. Cyclic alkenes
such as cyclopentene, cyclohexene, cycloheptene, and 1-
methylcyclohexene could react with chromone, giving the
corresponding products in good yields (3aj−3am). When
the more hindered norbornene was used in this protocol,
the reaction furnished product 3an (dr = 1.1:1) in 66% yield.
Additionally, the reaction of the cyclic alkene dihydrofuran
O
O
R1
0.3 equiv Fe(acac)3
3 equiv PhSiH3
R3
R3
+
R2
EtOH, 40 °C, 5 h
R4
O
R4
O
R1 R2
1a
2
3
3 equiv
O
O
O
O
O
O
O
O
OH
OH
3aa
3ab
3ac
68%
3ad
71%
65% (dr = 1.2:1)a
62% (dr = 1.1:1)a
O
O
O
O
O
OH
OH
O
O
O
NBoc
O
3af
83%
3ag
82%
3ah
3ae
72%
65% (dr = 1.07:1)a
O
O
O
O
O
O
O
O
O
O
3aj
63%
3ak
66%
3am
61%
3al
71%
3ai
66%
O
O
O
O
O
O
O
O
3an
3ao
29%
3ap
68% (dr = 1.06:1)a
66% (dr = 1.1:1)a
Scheme 2 Substrate scope of unactivated alkenes. Reaction conditions: 1a (0.3 mmol), 2 (3 equiv), Fe(acac)3 (0.3 equiv), PhSiH3 (3 equiv), EtOH (0.5
M), 40 °C, 5 h. Isolated yields are given. a Determined by 1H NMR analysis
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

D
X.-L. Chen et al.
Letter
Synlett
gave the desired product 3ao in moderate yield. Also, the
reaction occurred with dihydropyran to afford the product
in 68% yield (3ap).
O
O
R2
R1
O
0.3 equiv Fe(acac)3
3 equiv PhSiH3
R2
Next, the scope of substituted chromones was studied
in the process (Scheme 3). For example, 6-substituted chro-
mones with electron-donating substitutents such as methyl
or hydroxy served as viable acceptor in this process provid-
ing the products in good to excellent yields (3bf, 3cf). Addi-
tionally, 7-methoxychromone was applicable furnishing
the corresponding product in 69% yield (3df). In particular,
various halogen atom substitutions at the C6 position of
chromone were compatible with this process (3ef, 3ff, 3gf).
Notably, a highly conjugated aromatic substrate, 4H-ben-
zo[h]chromen-4-one reacted smoothly to give the desired
product in 60% yield (3hf). 3-Cyanochromone also was effi-
cient to provide the product in 75% yield (3if). It is notewor-
thy that 3-cyanochromone can be coupled with alkene 2f
on gram scale to give compound 3if in 73% yield, which
shows the potential application of this protocol (Equation 1).14
To gain insight into the possible reaction mechanism,
some control experiments were carried out (Scheme 4).
Omission of Fe(acac)3 resulted in only recovery of the start-
ing material, demonstrating that the Fe(III) catalyst is nec-
essary for the coupling. When the radical scavenger TEMPO
was added, product 3af was not observed, indicating that
the transformation proceeded through a radical pathway.
When the reaction was performed in the absence of alkene,
chromanone 4 was obtained in 40% yield. However, con-
ducting the reaction using chromanone 4 and alkene 2f un-
der standard conditions gave no product, indicating that
compound 4 is not involved in this transformation.
1
+
R1
OH
EtOH, 40 °C, 5 h
O
OH
3
2f
3 equiv
O
O
O
O
HO
OH
OH
3bf, 85%
3cf, 67%
O
O
F
OH
OH
O
O
O
3df, 69%
3ef, 70%
O
O
Br
Cl
OH
OH
O
O
3gf, 75%
3ff, 70%
O
O
CN
OH
OH
O
O
On the basis of these results and literatures reports,1-4
a
3hf, 60%
3if, 75%
plausible mechanism is proposed in Scheme 5. At the be-
ginning, the Fe catalyst is converted into Fe hydride in the
presence of PhSiH3 and EtOH. The following step involves
the transfer of a hydrogen atom from the transient Fe hy-
dride to the donor olefin 2f, giving the intermediate alkyl
radical A, which could be trapped by 1a to form radical ad-
duct B. Next, single-electron reduction of the radical by Ln-
Fem−1 would give the stabilized anion C. Finally, the stabi-
lized anion C is protonated with EtOH to provide the cou-
pled adduct D. The compound D transforms into the
desirable product 3af through tautomerism.
Scheme 3 Substrate scope of substituted chromones. Reaction condi-
tions: 1a (0.3 mmol), 2 (3 equiv), Fe(acac)3 (0.3 equiv), PhSiH3 (3 equiv),
EtOH (0.5 M), 40 °C, 5 h. Isolated yields are given.
In conclusion, we have developed a Fe(III)-catalyzed re-
ductive cross-coupling of unactivated olefins with chro-
mones. This process is operationally simple and has been
run under mild conditions. Furthermore, various alkenes
and differently substituted chromones are tolerated, afford-
ing the products in good to excellent yields. Therefore, this
method provides a practical route for the synthesis of 2-
alkylchromanones.
O
0.3 equiv Fe(acac)3
3 equiv PhSiH3
O
O
CN
CN
+
OH
EtOH, 40 °C, 5 h
OH
O
1i
1.36 g
2f
3 equiv
3if
73%, 1.51 g
Equation 1 The reaction of 1i with 2f on gram scale
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

E
X.-L. Chen et al.
Letter
Synlett
Supporting Information
O
3 equiv PhSiH3
Supporting information for this article is available online at
+
recovered 1a
OH
https://doi.org/10.1055/s-0036-1591601.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
o
nrtogI
f
rmoaitn
EtOH, 40 °C, 5 h
O
1a
2f
3 equiv
References and Notes
TEMPO
0.3 equiv Fe(acac)3
3 equiv PhSiH3
O
O
(1) (a) Crossley, S. W. M.; Obradors, C.; Martinez, R. M.; Shenvi, R. A.
Chem. Rev. 2016, 116, 8912. (b) Obradors, C.; Martinez, R. M.;
Shenvi, R. A. J. Am. Chem. Soc. 2016, 138, 4962. (c) Dao, H. T.; Li,
C.; Michaudel, Q.; Maxwell, B. D.; Baran, P. S. J. Am. Chem. Soc.
2015, 137, 8046. (d) Zheng, J.; Wang, D.; Cui, S. Org. Lett. 2015,
17, 4572. (e) Shen, Y.; Huang, B.; Zheng, J.; Lin, C.; Liu, Y.; Cui, S.
Org. Lett. 2017, 19, 1744. (f) Leggans, E. K.; Barker, T. J.; Duncan,
K. K.; Boger, D. L. Org. Lett. 2012, 14, 1428. (g) Zhu, K. L.; Shaver,
M. P.; Thomas, S. P. Chem. Sci. 2016, 7, 3031. (h) Villa, M.;
Wangelin, A. J. V. Angew. Chem. Int. Ed. 2015, 54, 11906.
(i) Zhang, N.; Quan, Z.; Wang, X. C. Adv. Synth. Catal. 2016, 358,
3179.
(2) (a) Lo, J. C.; Yabe, Y.; Baran, P. S. J. Am. Chem. Soc. 2014, 136,
1304. (b) Lo, J. C.; Gui, J.; Yabe, Y.; Pan, C.-M.; Baran, P. S. Nature
2014, 516, 343.
(3) Shen, Y.; Qi, J.; Mao, Z.; Cui, S. Org. Lett. 2016, 18, 2722.
(4) Lo, J. C.; Kim, D.; Pan, C.-M.; Edwards, J. T.; Yabe, Y.; Gui, J.; Qin,
T.; Gutiérrez, S.; Giacoboni, J.; Smith, M. W.; Holland, P. L.;
Baran, P. S. J. Am. Chem. Soc. 2017, 139, 2484.
+
OH
OH
EtOH, 40 °C, 5 h
O
O
1a
2f
3 equiv
3af not detected
O
O
0.3 equiv Fe(acac)3
3 equiv PhSiH3
EtOH, 40 °C, 5 h
40%
O
O
4
1a
O
O
standard conditions
+
OH
OH
O
O
4
2f
3 equiv
3af not detected
Scheme 4 Control experiments
(5) Chromanones: (a) Andersen, O. M.; Markham, K. R. Flavonoids:
Chemistry, Biochemistry and Applications; Taylor & Francis: Boca
Raton FL, 2006. (b) Ellis, G. P. Chromenes, Chromanones and
OH
OH
A
2f
Chromones; John Wiley
&
Sons: New
York, 1977.
(c) Nussbaumer, P.; Lehr, P.; Billich, A. J. Med. Chem. 2002, 45,
4310. (d) Zimmerman, J. R.; Manpadi, M.; Spatney, R.; Baker, A.
J. Org. Chem. 2011, 76, 8076. (e) Cozzi, P.; Branzoli, U.; Lovisolo,
P. P.; Orsini, G.; Carganico, G.; Pillan, A.; Chiari, A. J. Med. Chem.
1986, 29, 404. (f) Fridén-Saxin, M.; Seifert, T.; Landergren, M. R.;
Suuronen, T.; Lahtela-Kakkonen, M.; Jarho, E. M.; Luthman, K.
J. Med. Chem. 2012, 55, 7104.
LnFem
H
O
LnFem–1
O
PhSiH3
EtOH
1a
LnFem
(6) 2-Alkyl chromanones: (a) Nussbaumer, P.; Winiski, A. P.; Billich,
A. J. Med. Chem. 2003, 46, 5901. (b) Rodríguez-Ramos, F.;
Navarrete, A.; González-Andrade, M.; Alarcón, C.; Aguilera-Cruz,
A.; Reyes-Ramírez, A. Bioorg. Chem. 2013, 50, 17. (c) Liu, H.;
Dong, A.; Gao, C.; Tan, C.; Xie, Z.; Zu, X.; Qu, L.; Jiang, Y. Bioorg.
Med. Chem. 2010, 18, 6322. (d) Beekman, A. M.; Martinez, E. C.;
Barrow, R. A. Org. Biomol. Chem. 2013, 11, 1109. (e) Yang, L. Y.;
Yao, J. H.; Shu, L. D.; Shen, Y. Q.; Gao, X. M.; Hu, Q. F. Asian
J. Chem. 2013, 25, 8355.
O
O
OH
O
B
OH
O
C
EtOH
OH
O
(7) (a) Engbersen, J. F. J.; Koudijs, A.; van der Plas, H. C. J. Heterocy-
clic Chem. 1982, 19, 1281. (b) Saengchantara, S. T.; Wallace, T.
W. Tetrahedron 1990, 46, 6553. (c) Hodgetts, K. J.; Maragkou, K.
I.; Wallace, T. W.; Wootton, R. C. R. Tetrahedron 2001, 57, 6793.
(d) Albrecht, U.; Lalk, M.; Langer, P. Bioorg. Med. Chem. 2005, 13,
1531. (e) Brown, M. K.; Degrado, S. J.; Hoveyda, A. H. Angew.
Chem. Int. Ed. 2005, 44, 5306. (f) Stubbing, L. A.; Li, F. F.; Furkert,
D. P.; Caprio, V. E.; Brimble, M. A. Tetrahedron 2012, 68, 6948.
(8) Zimmerman, J. R.; Manpadi, M.; Spatney, R. Green Chem. 2011,
13, 3103.
OH
OH
O
D
O
3af
Scheme 5 Proposed mechanism
Funding Information
(9) Vila, C.; Hornillos, V.; Fañanás-Mastral, M.; Feringa, B. L. Chem.
Commun. 2013, 49, 5933.
(10) Zhao, J.; Fang, H.; Qian, P.; Han, J.; Pan, Y. Org. Lett. 2014, 16,
5342.
This work is supported by Science and Technology Department of
Sichuan Province under grant number 2015JY0171.
)(
(11) Hardman-Baldwin, A. M.; Visco, M. D.; Wieting, J. M.; Stern, C.;
Kondo, S.-I.; Mattson, A. E. Org. Lett. 2016, 18, 3766.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

F
X.-L. Chen et al.
Letter
Synlett
(12) Bichovski, P.; Haas, T. M.; Keller, M.; Streuff, J. Org. Biomol.
Chem. 2016, 14, 5673.
(13) Experimental Procedure and Characterization Data for Com-
pound 3af
2.77–2.61 (m, 2 H), 1.94 (s, 1 H), 1.80–1.77 (m, 1 H), 1.71–1.23
(m, 1 H), 1.06 (d, J = 4.8 Hz, 6 H) ppm. 13C NMR (75 Hz, CDCl3):
δ = 193.33, 161.80, 135.91, 126.84, 121.18, 120.72, 117.73,
84.23, 59.06, 40.95, 38.05, 36.11, 23.38, 23.12 ppm. HRMS (ESI):
m/z [M + H]+ calcd for C14H19O3+: 235.1328; found: 235.1327.
(14) Experimental Procedure for Compound 3if on Gram Scale
To a solution of substrate 1i (1.36 g, 8 mmol, 1 equiv) and
Fe(acac)3 (0.84 g, 2.4 mmol, 30 mol%) in EtOH (40 mL, 0.2 M)
were added olefin 2f (24 mmol, 3 equiv) and PhSiH3 (2 mL, 24
mmol, 3 equiv). The resulting mixture was heated in an oil bath
preheated to 40 °C with stirring for 5 h. The reaction mixture
was then cooled to room temperature, diluted with brine, and
extracted with EtOAc (3 × 20 mL). The combined organic layers
were washed with brine, dried with Na2SO4, filtered, and con-
centrated under reduced pressure. The resulting crude product
was then purified by column chromatography on silica gel
(petroleum ether/EtOAc = 3:1) to afford the desired product 3if
as a slightly yellow solid (1.51 g, 73% yield).
To a solution of chromone 1a (0.3 mmol, 1 equiv) and Fe(acac)3
(31.8 mg, 0.09 mmol, 30 mol%) in EtOH (1.5 mL, 0.2 M) were
added olefin 2f (0.9 mmol, 3 equiv) and PhSiH3 (74 μL, 0.9
mmol, 3 equiv). The resulting mixture was heated in an oil bath
preheated to 40 °C with stirring for 5 h. The reaction mixture
was then cooled to room temperature, diluted with brine, and
extracted with EtOAc (3 × 5 mL). The combined organic layers
were washed with brine, dried with Na2SO4, filtered, and con-
centrated under reduced pressure. The resulting crude product
was then purified by column chromatography on silica gel
(petroleum ether/EtOAc = 5:1) to afford the desired product 3af
as a colorless oil (58.3 mg, 83% yield). 1H NMR (300 MHz,
CDCl3): δ = 7.83 (dt, J = 7.5, 0.5 Hz, 1 H), 7.46–7.41 (m, 1 H), 7.0–
6.94 (m, 2 H), 4.14 (dd, J = 12.9, 3.6 Hz, 1 H), 3.80–3.75 (m, 2 H),
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F