A Borane-Catalyzed Metal-Free Hydrosilylation of Chromones and Flavones

Article abstract of DOI:10.1055/s-0036-1588474

A Piers-type hydrosilylation of chromones and flavones has been successfully realized for the first time using 0.1 mol % of borane catalyst generated in situ by hydroboration of pentafluorostyrene with HB(C ₆ F ₅) ₂ to afford a variety of chromanones and flavanones in 60-99% yields. An attempt for the asymmetric transformation with chiral diyne and HB(C ₆ F ₅) ₂ gave chromanones and flavanones in high yields with up to 32% ee.

Full text of DOI:10.1055/s-0036-1588474

SYNLETT
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© Georg Thieme Verlag Stuttgart · New York
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X. Ren et al.
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A Borane-Catalyzed Metal-Free Hydrosilylation of Chromones and
Flavones
Xiaoyu Rena,b
Caifang Hana,b,c
+
HB(C6F5)2
C6F5
(0.1 mol%)
Xiangqing Fenga,b
O
O
O
Haifeng Du*a,b
0
0
0
0
0-
0
0
3
0-
1
2
2
3-
7
3
5
H
PhMe2SiH
O
R
a Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory
of Molecular Recognition and Function, CAS Research/Education Center
for Excellence in Molecular Sciences, Institute of Chemistry, Chinese
Academy of Sciences, Beijing 100190, P. R. of China
R
up to 99% yield
32% ee
+
chiral diyne
HB(C6F5)2
(0.5 mol%)
haifengdu@iccas.ac.cn
b University of Chinese Academy of Sciences, Beijing 100049, P. R. of China
c College of Chemistry and Material Sciences, Hebei Normal University,
Shijiazhuang, Hebei 050024, P. R. of China
Published as part of the Cluster Silicon in Synthesis and Catalysis
Received: 28.04.2017
Accepted after revision: 29.05.2017
Published online: 06.07.2017
drogenation in the past decade.9,10 Despite these advances,
very limited examples for the Piers-type hydrosilylation of
α,β-unsaturated compounds have been reported. For exam-
ple, in 2012, Paradies and co-workers described a hydroge-
nation of silyl enol ether intermediates which was generat-
ed by B(C6F5)3-catalyzed hydrosilylation of enones.11 In
2016, Chang and co-workers reported a B(C6F5)3-catalyzed
hydrosilylation of α,β-unsaturated esters and amides.12 As
our ongoing interest in metal-free hydrogenation and hy-
drosilylation,13,14 we wish to devote our efforts to the hy-
drosilylaition of chromones and flavones for the synthesis
of chromanones and flavanones using an in situ generated
borane catalyst. Herein, we report our preliminary results
on this subject.
DOI: 10.1055/s-0036-1588474; Art ID: st-2017-b0302-c
Abstract A Piers-type hydrosilylation of chromones and flavones has
been successfully realized for the first time using 0.1 mol % of borane
catalyst generated in situ by hydroboration of pentafluorostyrene with
HB(C6F5)2 to afford a variety of chromanones and flavanones in 60–99%
yields. An attempt for the asymmetric transformation with chiral diyne
and HB(C6F5)2 gave chromanones and flavanones in high yields with up
to 32% ee.
Key words hydrosilylation, chromones, flavones, chromanones, flava-
nones, borane catalyst, alkene, chiral diyne
Chromanones and flavanones are an important class of
moieties contained in a wide range of biologically and me-
dicinally active compounds.1 Several methods have been
well-established for their synthesis, such as intermolecular
oxa-Michael additions and 1,4-additions with organome-
tallic reagents.2–4 In contrast, as a straightforward access to
chromanones and flavanones, direct reductions of chro-
mones and flavones, as well as the asymmetric transforma-
tions have been relatively less developed. Only a few exam-
ples on the hydrogenation of chromones and flavones have
been reported using transition-metal catalysts.5 In particu-
lar, to the best of our knowledge, as one of the most useful
reduction methodologies, the hydrosilylation has been
rarely employed for the synthesis of chromanones and fla-
vanones.
Initially, the metal-free hydrosilylation of chromone1a
was carried out with PhMe2SiH (1.2 equiv) using 1 mol% bo-
rane 2 in toluene at room temperature for six hours. As
shown in Scheme 1, B(C6F5)3 (2a)15 gave chromanone 3a in
28% conversion, and HB(C6F5)2 (2b)16 exhibited a much low-
er activity. To our pleasure, the in situ generated borane 2c
by hydroboration of pentafluorostyrene with HB(C6F5)2 was
highly effective for the hydrosilylation of chromone 1a to
furnish chromanone 3a in a quantitative conversion after
removal of the silyl group by trifluoroacetic acid.
1. borane 2 (1.0 mol%)
O
O
PhMe2SiH (1.2 equiv)
toluene, r.t., 6 h
2. CF3CO2H, r.t., 10 min
O
Me
O
Me
Since Piers and co-workers discovered an interesting Si–
H activation instead of substrate activation in the B(C6F5)3-
catalyzed hydrosilylation of carbonyl compounds in 1996,
Piers-type hydrosilylation has attracted intensive interest
in both synthetic and mechanistic aspects.6–8 Notably, some
important progress has been made for the asymmetric hy-
3a
1a
B(C6F5)3
2a
HB(C6F5)2
2b
+
HB(C6F5)2
C6F5
2c
28% conv.
9% conv.
>99% conv.
Scheme 1 Initial study on Piers-type hydrosilylation of chromones
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D

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X. Ren et al.
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2c (0.1 mol%)
1.
1. HB(C6F5)2 (0.1 mol%)
alkene (0.1 mol%)
O
O
PhMe2SiH (1.2 equiv)
toluene, 80 °C, 15 h
1a
3a
PhMe2SiH (1.2 equiv)
toluene, 80 °C, 15 h
2. CF3CO2H, r.t., 10 min
2. CF3CO2H, r.t., 10 min
>99% conv.
O
R
O
R
3a–l
1a–l
O
O
O
O
O
C6F5
Ph
alkene:
Me
O
Et
O
nPr
O
iPr
F3C
CF3
OMe
3a
3b
3c
3d
98%
99%
95%
78%
Scheme 2 Evaluation of alkenes for hydrosilylation of chromones
O
O
O
O
Me
It is important to note that the amount of catalyst 2c
can be reduced to 0.1 mol% when the reaction temperature
was raised to 80 °C and the reaction time was prolonged to
15 hours (Scheme 2) without loss of reactivity, to the best
of our knowledge, which belongs to one of the lowest cata-
lyst loadings for the Piers-type hydrosilylation. Moreover,
besides pentafluorostyrene, a variety of commercial avail-
able alkenes derived borane catalysts were found to be
highly efficient for the hydrosilylation reaction to lead a
quantitative conversion (Scheme 2). Under the optimal con-
ditions, a variety of chromones and flavones 1a–l were next
subjected to this hydrosilylation.17 As shown in Scheme 3,
chromones 1a–g were highly reactive substrates to afford
the desired chromanones 3a–g in 78–99% yields. In con-
trast, flavones 1h–l were slightly less reactive to give flava-
nones 3h–l in relatively lower yields.
O
3e
tBu
O
3f
Bn
O
3g
Me
O
3h
Ph
93%
82%
98%
80%
O
O
O
O
O
Me
F
O
3i
60%
3j
3k
75%
F
OMe
75%
O
O
3l
Me
84%
With these results in hand, the possibility for the asym-
metric hydrosilylation was tested by using 1 mol% of chiral
borane catalysts generated in situ by hydroboration of chi-
ral diene 4 or diyne 5 with HB(C6F5)2. As shown in Scheme
4, the reaction of chromone 1a proceeded smoothly to give
chromanone 3a in quantitative conversions but with disap-
pointing ee. Chiral diyne 5 seems to be a little better than
chiral diene 4 to give a slightly higher ee. Moreover, when a
frustrated Lewis pair of chiral diyne 5 derived borane and
tricyclohexylphosphine was utilized as catalyst, chroma-
none 3a was obtained in 92% conversion with 18% ee. A va-
riety of chromones and flavones were then examined for
the asymmetric hydrosilylation by using 1 mol % of chiral
diyne 5 derived borane. As shown in Figure 1, all these reac-
tions went well to produce the desired chromanones and
flavanones in 91–99% yields with 11–32% ee. Although the
enantioselectivity is not satisfactory, the current work rep-
resents the first example for the asymmetric hydrosilyla-
tion of chromones and flavones.
Scheme 3 Metal-free hydrosilylation of chromones and flavones
1. HB(C6F5)2 (1 mol%)
chiral diene 4 or diyne 5
(0.5 mol%)
O
O
O
O
PhMe2SiH (1.2 equiv)
Me
Me
toluene, r.t., 1 h
1a
2. CF3CO2H, r.t., 10 min
3a
tBu
>99% conv.
tBu
tBu
tBu
tBu
tBu
tBu
21% ee
tBu
4
5
In summary, a metal-free hydrosilylation of chromones
and flavones was successfully realized for the first time
with the use of in situ generated borane catalyst by hydrob-
oration of pentafluorostyrene with HB(C6F5)2. A variety of
chromanones and flavanones were obtained in 60–99%
yields. It is noteworthy that only 0.1 mol % catalyst loading
15% ee
Scheme 4 Chiral borane derived from chiral diene or diyne for asym-
metric hydrosilyaltion of chromones
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D

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(4) For selected reports, see: (a) Chen, J.; Chen, J.; Lang, F.; Zhang,
X.; Cun, L.; Zhu, J.; Deng, J.; Liao, J. J. Am. Chem. Soc. 2010, 132,
4552. (b) Korenaga, T.; Hayashi, K.; Akaki, Y.; Maenishi, R.;
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2015, 10, 540.
(5) (a) Valla, C.; Baeza, A.; Menges, F.; Pfaltz, A. Synlett 2008, 3167.
(b) Zhao, D.-B.; Beiring, B.; Glorius, F. Angew. Chem. Int. Ed.
2013, 52, 8454.
O
O
O
O
O
O
tBu
O
nPr
Et
O
Me
3a
3b
91% (17% ee)
3c
99% (11% ee)
3e
98% (21% ee)
Me
95% (32% ee)
O
O
O
O
O
O
Ph
3-FC6H4
Me
(6) Parks, D. J.; Piers, W. E. J. Am. Chem. Soc. 1996, 118, 9440.
(7) Oesteich, M.; Hermeke, J.; Mohr, J. Chem. Soc. Rev. 2015, 44,
2202.
3g
99% (17% ee)
3h
3j
99% (11% ee)
O
93% (17% ee)
(8) For selected reports, see: (a) Blackwell, J. M.; Foster, K. L.; Beck,
V. H.; Piers, W. E. J. Org. Chem. 1999, 64, 4887. (b) Blackwell, J.
M.; Sonmor, E. R.; Scoccitti, T.; Piers, W. E. Org. Lett. 2000, 2,
3921. (c) Berkefeld, A.; Piers, W. E.; Parvez, M. J. Am. Chem. Soc.
2010, 132, 10660. (d) Simonneau, A.; Oestreich, M. Angew.
Chem. Int. Ed. 2013, 52, 11905. (e) Pérez, M.; Hounjet, L. J.;
Caputo, C. B.; Dobrovetsky, R.; Stephan, D. W. J. Am. Chem. Soc.
2013, 135, 18308. (f) Adduci, L. L.; McLaughlin, M. P.; Bender, T.
A.; Becker, J. J.; Gagné, M. R. Angew. Chem. Int. Ed. 2014, 53,
1646. (g) Houghton, A. Y.; Hurmalainen, J.; Mansikamäki, A.;
Piers, W. E.; Tuononen, H. M. Nat. Chem. 2014, 6, 983.
(h) Gandhamsetty, N.; Joung, S.; Park, S.-W.; Park, S.; Chang, S.
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J.; Jeong, J.; Park, S.-W.; Park, S.; Chang, S. Angew. Chem. Int. Ed.
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Int. Ed. 2015, 54, 8250. (l) Simonneau, A.; Oestreich, M. Nat.
Chem. 2015, 7, 816.
O
3-OMeC6H4
3k
94% (17% ee)
Figure 1 Asymmetric hydrosilylation of chromones and flavones
can ensure a high reactivity. Significantly, an attempt for
the asymmetric hydrosilylation of chromones and flavones
using chiral diyne derived catalyst gave chromanones and
flavanones in high yields with up to 32% ee. Further efforts
on searching for more effective chiral catalysts for this
transformation are under way in our laboratory.
(9) Feng, X.; Du, H. Tetrahedron Lett. 2014, 55, 6959.
Funding Information
(10) (a) Rendler, S.; Oestreich, M. Angew. Chem. Int. Ed. 2008, 47,
5997. (b) Hog, D. T.; Oestreich, M. Eur. J. Org. Chem. 2009, 5047.
(c) Mewald, M.; Oestreich, M. Chem. Eur. J. 2012, 18, 14079.
(d) Hermeke, J.; Mewald, M.; Oestreich, M. J. Am. Chem. Soc.
2013, 135, 17537. (e) Chen, D.; Leich, V.; Pan, F.; Klankermayer,
J. Chem. Eur. J. 2012, 18, 5184. (f) Süsse, L.; Hermeke, J.;
Oestreich, M. J. Am. Chem. Soc. 2016, 138, 6940.
We are grateful for the generous financial support by the National
Natural Science Foundation of China (21222207, 21572231,
21521002).
N
oaitn
a
l
Natuarl
Secince
F
o
u
n
d
oaitn
of
C
h
n
i
a
2(
1
2
2
2
2
0
7)
2(
1
5
7
2
2
3
1)
2(
1
5
2
1
0
0
2)
Supporting Information
(11) Greb, L.; Oña-Burgos, P.; Kubas, A.; Falk, F. C.; Breher, F.; Fink, K.;
Paradies, J. Dalton Trans. 2012, 41, 9056.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1588474.
(12) Kim, Y.; Chang, S. Angew. Chem. Int. Ed. 2016, 55, 218.
(13) (a) Liu, Y.; Du, H. J. Am. Chem. Soc. 2013, 135, 6810. (b) Wei, S.;
Du, H. J. Am. Chem. Soc. 2014, 136, 12261. (c) Ren, X.; Li, G.; Wei,
S.; Du, H. Org. Lett. 2015, 17, 990. (d) Zhang, Z.; Du, H. Org. Lett.
2015, 17, 2816. (e) Zhang, Z.; Du, H. Org. Lett. 2015, 17, 6266.
(14) (a) Zhu, X.; Du, H. Org. Biomol. Chem. 2015, 13, 1013. (b) Ren, X.;
Du, H. J. Am. Chem. Soc. 2016, 138, 810.
S
u
p
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ortiInfogrmoaitn
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References and Notes
(1) (a) Chemistry of Heterocyclic Compounds: Chromens, Chroma-
nones, and Chromones;
3
V1o.
l
Ellis, G.-P., Ed.; John Wiley and Sons:
(15) Massey, A. G.; Park, A. J. J. Organometallic Chem. 1964, 2, 245.
(16) (a) Parks, D. J.; von H. Spence, R. E.; Piers, W. E. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 809. (b) Parks, D. J.; Piers, W. E.; Yap, G. P.
A. Organometallics 1998, 17, 5492.
New York, 1977. (b) Flavonoids: Chemistry, Biochemistry and
Applications; Andersen, Ø. M., Ed.; CRC, Taylor and Francis: Boca
Raton, 1986. (c) Flavonoids: Biosynthesis, Biological Effects and
Dietary Sources; Keller, R. B., Ed.; Nova Science: Hauppauge,
2009.
(17) General Procedure for Hydrosilylations
To a tube, HB(C6F5)2 (0.0035 g, 0.01 mmol), 2,3,4,5,6-pentafluo-
rostyrene (0.0019 g, 0.01 mmol), and dry toluene (0.10 mL)
were added in a nitrogen atmosphere glovebox. The resulting
mixture was stirred for 5 min at r.t. to afford a catalyst solution
(0.10 M). To a sealing tube (15 mL), catalyst solution (0.0004
mmol, 4 μL, 0.1 M), PhMe2SiH (0.0649 g, 0.48 mmol), chromone
or flavone 1(0.0644 g, 0.4 mmol), and dry toluene (0.8 mL) were
added. The reaction mixture was stirred at 80 °C for 15 h, and
(2) (a) Kulkarni, P. R. Org. Chem.: Indian J. 2014, 10, 417. (b) Meng,
L.; Wang, J. Synlett 2016, 27, 656.
(3) For selected reports, see: (a) Biddle, M. M.; Lin, M.; Scheidt, K. A.
J. Am. Chem. Soc. 2007, 129, 3830. (b) Wang, L.-J.; Liu, X.-H.;
Dong, Z.-H.; Fu, X.; Feng, X.-M. Angew. Chem. Int. Ed. 2008, 47,
8670. (c) Wang, H.-F.; Cui, H.-F.; Chai, Z.; Li, P.; Zheng, C.-W.;
Yang, Y.-Q.; Zhao, G. Chem. Eur. J. 2009, 15, 13299.
(d) Hintermann, L.; Dittmer, C. Eur. J. Org. Chem. 2012, 5573.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D

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then was cooled to r.t. followed by addition of TFA (0.0547 g,
0.48 mmol). The resulting mixture stirred at r.t. for 10 min and
was concentrated and purified by column chromatography on
silica gel to afford the corresponding products 3.
2-(2-Fluorophenyl)chroman-4-one (3i)
Light yellow oil, 0.0582 g, 60% yield. 1H NMR (400 MHz, CDCl3):
δ = 7.95 (d, J = 7.6 Hz, 1 H), 7.64 (dd, J = 7.6, 7.6 Hz, 1 H), 7.52
(dd, J = 8.6, 8.0 Hz, 1 H), 7.40–7.32 (m, 1 H), 7.27–7.20 (m, 1 H),
7.14–7.04 (m, 3 H), 5.79 (dd, J = 13.2, 2.8 Hz, 1 H), 3.06 (dd, J =
16.8, 13.2 Hz, 1 H), 2.93 (dd, J = 16.8, 3.2 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 191.6, 161.6, 159.7 (d, JC–F = 246.0 Hz),
136.3, 130.3 (d, JC–F = 9.0 Hz), 127.6 (d, JC–F = 4.0 Hz), 127.2, 126.3
(d, JC–F = 13.0 Hz), 124.7 (d, JC–F = 3.0 Hz), 121.9, 121.0, 118.2,
115.8 (d, JC–F = 21.0 Hz), 73.9 (d, JC–F = 3.0 Hz), 43.8 ppm.19F NMR
(470 MHz, CDCl3): δ = –121.8 ppm.
2-Isopropylchroman-4-one (3d)
Colorless oil, 0.0593 g, 78% yield. 1H NMR (400 MHz, CDCl3): δ =
7.87 (d, J = 7.6 Hz, 1 H), 7.46 (dd, J = 8.0, 7.6 Hz, 1 H), 6.99 (m, 2
H), 4.21–4.16 (m, 1 H), 2.75–2.62 (m, 2 H), 2.12–2.18 (m, 1 H),
1.08 (d, J = 6.8 Hz, 3 H), 1.05 (t, J = 6.8 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 193.1, 162.0, 136.0, 127.0, 121.1, 121.0,
118.0, 82.6, 40.1, 32.2, 17.92, 17.90 ppm.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D