Synthesis of 8-amino-(dihydrofuran-fused perhydrophenanthrene) via copper-mediated amination reaction

Article abstract of DOI:10.3987/COM-13-S(S)38

Introduction of nitrogen substituents on a highly functionalized dihydrofuran-fused perhydrophenanthrene (DF) core was examined. Acetamide functionality could be introduced on the DF by copper-mediated Buchwald-type coupling. On the other hand, installation of free amino group on a DF was established via an aryl azide under the copper-mediated condition reported by Helquist and co-workers.

Full text of DOI:10.3987/COM-13-S(S)38

HETEROCYCLES, Vol. 88, No. 1, 2014
755
HETEROCYCLES, Vol. 88, No. 1, 2014, pp. 755 - 763. © 2014 The Japan Institute of Heterocyclic Chemistry
Received, 19th June, 2013, Accepted, 25th July, 2013, Published online, 29th July, 2013
DOI: 10.3987/COM-13-S(S)38
SYNTHESIS OF 8-AMINO-(DIHYDROFURAN-FUSED
PERHYDROPHENANTHRENE) VIA COPPER-MEDIATED
AMINATION REACTION
a
a
b
a,
Kenji Sugimoto, Kosuke Tamura, Noaki Toyooka, and Yuji Matsuya *
a
Graduate School of Medicine and Pharmaceutical Sciences for Research,
b
University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan, Graduate School
of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama
9
30-8555, Japan. E-mail: matsuya@pha.u-toyama.ac.jp
This paper is dedicated to Professor Victor Snieckus on the occasion of his 77th
birthday.
Abstract – Introduction of nitrogen substituents on a highly functionalized
dihydrofuran-fused perhydrophenanthrene (DF) core was examined. Acetamide
functionality could be introduced on the DF by copper-mediated Buchwald-type
coupling. On the other hand, installation of free amino group on a DF was
established via an aryl azide under the copper-mediated condition reported by
Helquist and co-workers.
Naturally occurring biologically active pentacyclic polyketides such as halenaquinone, halenaquinol, and
1
xestoquinone were known to possess furan-fused highly oxygenated structure. Their structural and
2
biological feature attracted synthetic organic chemists and we also developed an effective preparation of
3
similar tetracyclic dihydrofurans (DFs) using originally elaborated o-quinodimethane chemistry. The
biological evaluations on our DFs revealed that they show several fascinating biological activities. Firstly,
4
dihydrofuran 1 was proved to exhibit anti-virus activity against HVJ. This dihydrofuran 1 also showed
5
dose-dependent enhancement of a heat-induced apoptosis in human lymphoma U937 cells. Further
structure-activity-relationship studies afforded potent anti-influenza agents, trifluoromethyl ether 2 and
6
3
,5-difluorobenzyl ether 3. Additionally, 4 has been expected as novel anti-Alzheimer’s disease agent for
7
its axonal and dendritic extension activities in A!-damaged neurons. Recently, extensive SAR studies on
4
suggested the efficiency of the introduction of hetero atom on the C8 position and finally proved that
8
EtO- (5) or PhS- (6) substituent markedly enhance the dendritic extension effect. However, we could

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HETEROCYCLES, Vol. 88, No. 1, 2014
never have estimated the dendritic extension activities of nitrogen-introduced analogues for its difficulty
8
in installing nitrogen functionalities on the common precursor in our previous report. Thus, the
importance of the hetero atoms on the C8 position of DFs prompted us to develop a reaction which enable
the late-stage introduction of amino group on DFs. We describe herein the synthesis of 8-amino-DFs 7,
which could be a pivotal intermediate for further SAR studies, via copper-mediated amination reaction.
Figure 1. Natural and designed, biologically active fused furans
Prior to the synthetic studies, we examined a Cu-mediated introduction of N-methylacetamide on a simple
9
,10
model substrate, o-iodophenols under the conditions reported by Buchwald and co-workers (Table 1).
The coupling reaction of o-(TBSO)-iodobenzene (8a) with N-methylacetamide (2 eq) was conducted in
the presence of CuI (1 eq), DMEDA (2 eq) and K PO (2 eq), at 100 °C in DMSO to give a complex
3
4
mixture including o-iodophenol (8b) as a detectable product (entry 1). Dehalogenation reaction
dominantly proceeded with o-iodophenol (8b) as a substrate (entry 2). On the other hand,
o-(p-methoxybenzyloxy)-iodobenzene (8c) afforded corresponding acylanilide 9c in 7% yield (entry 3).
The addition of (±)-trans-1,2-cyclohexanediamine as a ligand slightly improve the yield of 9c to 20%
(entry 4).

HETEROCYCLES, Vol. 88, No. 1, 2014
757
Table 1. Cu-mediated amidation of DF with N-methylacetamide
With these results, we examined an installation of N-acetyl-N-methyl amino group on our
8
dihydrofuran-fused perhydrophenanthrene 10 as depicted in Scheme 1. Phenolic hydroxyl group was
uneventfully protected as DMB ether 11, which could be cleaved under a milder condition than that for
PMB ether. Cu-mediated coupling between 11 and N-methylacetamide took place to afford the
corresponding anilide 12 in 18% yield accompanied with inevitable decomposition of the substrate
including dehalogenation reaction.
Scheme 1. Introduction of N-Ac-N-Me amino group on DF
Aiming at the synthesis and biological evaluation of broad nitrogen-substituted DFs, next we examined a
preparation of the pivotal free aniline derivative. As indicated in Table 2, Cu-mediated amination reaction
1
1
with NaN , which was reported by Helquist and co-workers, was employed on o-iodophenols. Although,
3
similar to the amidation reaction, unprotected phenolic hydroxyl group would prevent the desired

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HETEROCYCLES, Vol. 88, No. 1, 2014
amination reaction (entry 1), o-(p-methoxybenzyloxy)-iodobenzene worked well to provide the aniline
3c in 40% yield (entry 2). Finally, it was found that 8c was effectively transformed into the desired 13c
with 52% in the presence of the excess amount of NaN (entry 4).
1
3
Table 2. Cu-mediated amination reaction with NaN3
Under the optimal condition, DF 11 could be converted into desired aniline 14, pivotal aniline congener
for further derivatization, in good yield (66%) as denoted in Scheme 2.
Scheme 2. Cu-mediated amination of DF
Finally, cleavage of the DMB group on the anilide 12 was performed as Scheme 3. Under quite mild
condition such as DDQ in basic media, DF 15 was successfully obtained in 58% remaining the acid labile,
acetal and dihydrofuran functional groups untouched.

HETEROCYCLES, Vol. 88, No. 1, 2014
759
Scheme 3. Successful oxidative cleavage of DMB ether
In summary, we investigated the late-stage introduction of amino group into biologically potent DF core
and could fortunately establish the key aniline derivatives in good yield based on Cu-mediated amination
strategy. Further derivatization from the common aniline 14 and biological evaluation of the
nitrogen-substituents on DFs are now in progress in our laboratory.
EXPERIMENTAL
Materials were obtained from commercial suppliers and used without further purification. Column
chromatography was performed on Cica Silica Gel 60 N (spherical, neutral, 40–50 µm or 63–210 µm).
Reaction and chromatographical fractions were monitored by employing precorted silica gel 60 F plates
2
54
(Merck). All melting points were determined on Yanaco micro melting point apparatus and uncorrected.
1
NMR spectra were recorded on JEOL ECX 400 spectrometer with CHCl (7.26 ppm for H) or CDCl
3
3
1
3
(
77.0 ppm for C) as an internal standard. Chemical shifts are expressed in " (ppm) values, and coupling
constants are expressed in hertz (Hz). The following abbreviations are used: s = singlet, d = doublet, t =
triplet, q = quartet, m = multiplet, br s = broad singlet, dd = double-doublet, dt = double-triplet, td =
triple-doublet, tt = triple-triplet, ddd = double-double-doublet, dddd = double-double-double-doublet. IR
spectra were measured on JASCO FT/IR-660. MS spectra were recorded on JEOL D-200, JEOL
JMS-GCmateII or JEOL AX 505 spectrometer.
General Procedure for Cu-mediated Amidation Reaction of Aryl Iodide (Table 1).
Under an Ar atmosphere, to a solution of the aryl iodide 8c (100 µmol) in dioxane (0.2 M) were added
N-methylacetamide (2 eq), CuI (1 eq), ligand (2 eq), and K PO (2 eq) at rt, and the mixture was stirred at
3
4
1
00 °C until the starting material was completely consumed (monitored by TLC). The reaction mixture
was then cooled to rt, diluted with saturated aqueous NH Cl and AcOEt, and stirred for 40 min at rt. After
4
filtration through Celite, the aqueous phase was extracted with AcOEt. The combined organic layers were
dried over MgSO , filtered, and concentrated in vacuo. The resulting oil was purified by column
4
chromatography on silica gel (AcOEt/hexane, 3:1, v/v) to afford the amide 9c.
8
-Iodo-9-(3,4-dimethoxy-benzyloxy)-3-[1.3]dioxolan-2,3,5a,10c-tetrahydro-1H,6H-5-oxaacephenan-
thrylene-10b-carbonitrile (11): Under an Ar atmosphere, to a solution of 3,4-dimethoxy-benzyl alcohol

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HETEROCYCLES, Vol. 88, No. 1, 2014
(
272 mg, 1.62 mmol) in CH Cl (8.1 mL) was added dropwise PBr (305 µL, 3.24 mmol) at 0 °C, and the
2
2
3
mixture was stirred for 8 h. The reaction was quenched with H O, and the aqueous phase was extracted
2
with CHCl . The combined organic layers were washed with brine, dried over MgSO , filtered, and
3
4
concentrated in vacuo. The resulting bromide was used without purification. Under an Ar atmosphere, to
8
a solution of the phenol 10 (341 mg, 780 µmol) and the above bromide in DMF (3.9 mL) was added
K CO (216 mg, 1.62 µmol) at 0 °C, and the mixture was stirred for 8 h at rt. The reaction was quenched
2
3
with H O, and the aqueous phase was extracted with Et O. The combined organic layers were washed
2
2
with brine, dried over MgSO , filtered, and concentrated in vacuo. The resulting oil was purified by
4
column chromatography on silica gel (AcOEt/CH Cl , 1:100, v/v) to afford the benzyl ether 11 (416 mg,
2
2
1
7
08 µmol, 91%) as a colorless solid (mp 192–193 °C); H-NMR (400 MHz, CDCl ) ": 1.66 (1H, ddd, J =
3
3
.7, 13.7, 14.2 Hz), 1.77 (1H, ddd, J = 3.7, 3.7, 13.7 Hz), 2.52 (1H, ddd, J = 3.7, 14.2, 14.7 Hz), 2.74 (1H,
td, J = 3.7, 14.7 Hz), 3.07 (1H, dd, J = 2.3, 15.8 Hz), 3.18 (1H, dd, J = 3.2, 15.8 Hz), 3.84–4.01 (11H, m),
5
1
7
7
1
5
.02 (1H, d, J = 11.4 Hz), 5.10 (1H, d, J = 11.4 Hz), 5.26 (1H, ddd, J = 2.3, 3.2, 10.5 Hz), 6.01 (1H, d, J =
.8 Hz), 6.77 (1H, s), 6.86 (1H, d, J = 8.0 Hz), 6.96 (1H, dd, J = 1.8, 8.0 Hz), 7.07 (1H, d, J = 1.8 Hz),
1
3
.72 (1H, s); C-NMR (100 MHz, CDCl ) ": 29.2, 29.7, 31.3, 32.6, 35.8, 50.9, 55.9, 55.9, 63.7, 65.3,
3
1.6, 79.6, 87.6, 104.4, 110.1, 110.5, 111.1, 119.5, 121.4, 128.6, 129.8, 132.3, 140.9, 143.3, 148.9, 149.2,
–
1
+
56.8; IR (KBr): 2240 cm ; MS (EI): m/z 587 (M ); HRMS (EI): calcd for C H INO : 587.0805, found:
2
7
26
6
87.0800.
N-[10b-Cyano-9-(3,4-dimethoxy-benzyloxy)-3-[1.3]dioxolan-2,3,5a,10c-tetrahydro-1H,6H-5-oxaace-
phenanthrylene-8-yl]-N-methyl-acetamide (12): Under an Ar atmosphere, to a solution of the iodide 11
(
32.3 mg, 55.0 µmol) in dioxane (275 µL) were added N-methylacetamide (8.40 µL, 110 µmol), CuI
10.5 mg, 55.0 µmol), (±)-trans-1,2-cyclohexanediamine (13.2 µL, 110 µmol), and K PO (29.3 mg, 110
(
3
4
µmol) at rt, and the mixture was stirred for 4 h at 100 °C. Then to the reaction mixture were further added
N-methylacetamide (8.40 µL, 110 µmol), CuI (10.5 mg, 55.0 µmol), (±)-trans-1,2-cyclohexanediamine
(
13.2 µL, 110 µmol), and K PO (29.3 mg, 110 µmol), and the mixture was stirred for 15 h at 100 °C. The
3 4
reaction mixture was then cooled to rt, diluted with saturated aqueous NH Cl and AcOEt, and stirred for
4
4
0 min at rt. After filtration through Celite, the aqueous phase was extracted with AcOEt. The combined
organic layers were dried over MgSO , filtered, and concentrated in vacuo. The resulting oil was purified
4
by column chromatography on silica gel (AcOEt/hexane, 3:1, v/v) to afford the amide 12 (5.3 mg, 9.95
1
µmol, 18%) as a colorless oil; H-NMR (400 MHz, CDCl ) ": 1.62–1.93 (5H, m), 2.53–2.62 (1H, m),
3
2
3
.78 (1H, dd, J = 2.7, 14.7 Hz), 3.09 (1H, d, J = 16.0 Hz), 3.17 (3H, s), 3.21 (1H, dd, J = 3.2, 16.0 Hz),
.83–4.05 (11H, m), 4.99 (1H, d, J = 11.4 Hz), 5.05 (1H, d, J = 11.4 Hz), 5.30 (1H, ddd, J = 3.2, 5.5, 10.1
1
3
Hz), 6.03 (1H, d, J = 1.8 Hz), 6.84–6.88 (3H, m), 6.95 (1H, s), 7.10 (1H, s); C-NMR (100 MHz, CDCl )
3
": 21.9, 25.9, 29.6, 31.9, 32.9, 35.7, 36.1, 51.0, 53.8, 55.9, 63.8, 65.3, 70.7, 79.5, 104.4, 110.1, 110.2,

HETEROCYCLES, Vol. 88, No. 1, 2014
761
111.2, 111.8, 119.4, 125.1, 128.6, 130.6, 131.7, 133.6, 143.4, 149.3, 153.3, 171.1; IR (neat): 1660, 2223
–
1
+
cm ; MS (EI): m/z 532 (M ); HRMS (EI): calcd for C H N O : 532.2210, found: 532.2210.
3
0
32
2
7
General Procedure for Cu-mediated Amination Reaction of Aryl Iodide (Table 2).
Under an Ar atmosphere, to a solution of the iodide 8c (100 µmol) in DMSO (0.3 M) were added NaN3
(2~10 eq), CuI (1 eq), and DMEDA (1.3 eq) at rt, and the mixture was stirred for 1 h at 100 °C. The
reaction mixture was then cooled to rt, diluted with saturated aqueous NH Cl and AcOEt, and stirred for 1
4
h at rt. The mixture was filtered through Celite, and the aqueous phase was extracted with AcOEt. The
combined organic layers were washed with brine, dried over MgSO , filtered, and concentrated in vacuo.
4
The resulting oil was purified by column chromatography on silica gel (AcOEt/hexane, 1:1, v/v) to afford
the amine 13c.
8
-Amino-9-(3,4-dimethoxy-benzyloxy)-3-[1.3]dioxolan-2,3,5a,10c-tetrahydro-1H,6H-5-oxaacephe-
nanthrylene-10b-carbonitrile (14): Under an Ar atmosphere, to a solution of the iodide 11 (25.7 mg,
3.8 µmol) in DMSO (146 µL) were added NaN (28.5 mg, 438 µmol), CuI (8.3 mg, 43.8 µmol), and
4
3
DMEDA (6.12 µL, 56.9 µmol) at rt, and the mixture was stirred for 1 h at 100 °C. The reaction mixture
was then cooled to rt, diluted with saturated aqueous NH Cl and AcOEt, and stirred for 1 h at rt. The
4
mixture was filtered through Celite, and the aqueous phase was extracted with AcOEt. The combined
organic layers were washed with brine, dried over MgSO , filtered, and concentrated in vacuo. The
4
resulting oil was purified by column chromatography on silica gel (AcOEt/hexane, 1:1, v/v) to afford the
1
amine 14 (13.7 mg, 28.8 µmol, 66%) as a colorless oil; H-NMR (400 MHz, CDCl ) ": 1.75–1.84 (2H, m),
3
2
.44–2.52 (1H, m), 2.74 (1H, ddd, J = 3.2, 3.2, 14.7 Hz), 2.98 (1H, dd, J = 2.3, 16.0 Hz), 3.15 (1H, dd, J
3.7, 16.0 Hz), 3.84–4.01 (11H, m), 4.93 (1H, d, J = 10.7 Hz), 4.99 (1H, d, J = 10.7 Hz), 5.25 (1H, ddd,
J = 2.3, 3.7, 10.5 Hz), 6.03 (1H, d, J = 1.8 Hz), 6.63 (1H, s), 6.75 (1H, s), 6.87 (1H, d, J = 8.2 Hz),
=
1
3
6
6
1
4
.95–6.96 (2H, m); C-NMR (100 MHz, CDCl ) ": 29.2, 29.8, 31.3, 33.1, 35.3, 51.0, 55.9, 55.9, 63.6,
3
5.3, 71.2, 79.9, 104.7, 110.4, 110.9, 111.1, 116.7, 119.6, 120.4, 122.5, 128.4, 129.3, 137.0, 143.2, 145.5,
–
1
+
49.0, 149.1; IR (neat): 2226, 3374 cm ; MS (EI): m/z 476 (M ); HRMS (EI): calcd for C H N O :
2
7
28
2
6
76.1947, found:476.1970.
N-[10b-Cyano-9-hydroxy-3-[1.3]dioxolan-2,3,5a,10c-tetrahydro-1H,6H-5-oxaacephenanthrylene-8-
yl]-N-methyl-acetamide (15): To a solution of benzyl ether 12 (7.9 mg, 14.8 µmol) in CH Cl /sat.
2
2
NaHCO aq. (150 µL, 9:1, v/v) was added DDQ (13.4 mg, 59.2 µmol), and the mixture was stirred for 5 h
3
at rt. The reaction mixture was diluted with saturated aqueous NaHCO , and the aqueous phase was
3
extracted with CH Cl . The combined organic layers were dried over MgSO , filtered, and concentrated in
2
2
4
vacuo. The resulting oil was purified by column chromatography on silica gel (MeOH/CH Cl , 1:50, v/v)
2
2
1
to afford the phenol 15 (3.3 mg, 8.63 µmol, 58%) as a colorless oil; H-NMR (400 MHz, CDCl ) ":
3
1
.82–2.04 (5H, m), 2.56 (1H, ddd, J = 4.1, 14.7, 14.7 Hz), 2.84 (1H, d, J = 14.7 Hz), 3.07 (1H, d, J = 16.0

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HETEROCYCLES, Vol. 88, No. 1, 2014
Hz), 3.20–3.25 (4H, m), 3.88–4.04 (5H, m), 5.30 (1H, ddd, J = 2.7, 5.5, 10.5 Hz), 6.06 (1H, d, J = 1.4 Hz),
1
3
7
6
2
.01 (1H, s), 7.04 (1H, s); C-NMR (100 MHz, CDCl ) ": 22.3, 29.7, 31.3, 32.8, 35.6, 36.2, 40.5, 50.9,
3
3.8, 65.4, 79.5, 104.6, 110.4, 115.9, 127.7, 129.4, 130.3, 132.7, 143.2, 151.6, 172.5; IR (neat): 1636,
–
1
+
231, 3223 cm ; MS (EI): m/z 382 (M ); HRMS (EI): calcd for C H N O : 382.1529, found: 382.1508.
2
1
22
2
5
ACKNOWLEDGEMENT
This study was supported by Health and Welfare Department of Toyama Prefectural Government
Toyama, Japan).
(
REFERENCES AND NOTES
1.
For halenaquinones, see (a) D. M. Roll, P. J. Scheuer, G. K. Matsumoto, and J. Clardy, J. Am. Chem.
Soc., 1983, 105, 6177; (b) M. Kobayashi, N. Shimizu, Y. Kyogoku, and I. Kitagawa, Chem. Pharm.
Bull., 1985, 33, 1305; (c) R. H. Lee, D. L. Slate, R. Moretti, K. A. Alvi, and P. Crews, Biochem.
Biophys. Res. Commun., 1992, 184, 765; (d) K. A. Alvi, M. C. Diaz, P. Crews, D. L. Slate, and R.
Lee, J. Org. Chem., 1992, 57, 6604; For halenaquinols, see (e) M. Kobayashi, N. Shimizu, I.
Kitagawa, Y. Kyogoku, N. Harada, and H. Uda, Tetrahedron Lett., 1985, 26, 3833; (f) N. Harada, H.
Uda, M. Kobayashi, N. Shimizu, and I. Kitagawa, J. Am. Chem. Soc., 1989, 111, 5668; (g) S.
Ikegami, N. Kajiyama, Y. Ozaki, Y. Myotoishi, S. Miyashiro, S. Takayama, M. Kobayashi, and I.
Kitagawa, FEBS Lett., 1992, 302, 284; For xestquinones, see (h) H. Nakamura, J. Kobayashi, M.
Kobayashi, Y. Ohizumi, and Y. Hirata, Chem. Lett., 1985, 713; (i) M. Kobayashi, H. Nakamura, J.
Kobayashi, and Y. Ohizumi, J. Pharmacol. Exp. Ther., 1991, 257, 82; (j) M. Kobayashi, A.
Muroyama, H. Nakamura, J. Kobayashi, and Y. Ohizumi, J. Pharmacol. Exp. Ther., 1991, 257, 90;
(k) H. Sakamoto, K. Furukawa, K. Matsunaga, H. Nakamura, and Y. Ohizumi, Biochemistry, 1995,
3
4, 12570.
2
.
For total syntheses of related natural products, see (a) N. Harada, T. Sugioka, Y. Ando, H. Uda, and T.
Kuriki, J. Am. Chem. Soc., 1988, 110, 8483; (b) N. Harada, T. Sugioka, H. Uda, and T. Kuriki, J. Org.
Chem., 1994, 59, 6606; (c) A. Kojima, T. Takemoto, M. Sodeoka, and M. Shibasaki, J. Org. Chem.,
1
996, 61, 4876; (d) S. P. Maddaford, N. G. Anderson, W. A. Cistofoli, and B. A. Keay, J. Am. Chem.
Soc., 1996, 118, 10766; (e) H. S. Sutherland, K. C. Higgs, N. Taylor, and R. Rodrigo, Tetrahedron,
001, 57, 309.
2
3
4
.
.
(a) N. Toyooka, M. Nagaoka, and H. Nemoto, Synlett, 2001, 1123; (b) N. Toyooka, M. Nagaoka, E.
Sasaki, H. Qin, H. Kakuda, and H. Nemoto, Tetrahedron, 2002, 58, 6097; (c) Y. Matsuya, H. Qin, M.
Nagaoka, and H. Nemoto, Heterocycles, 2004, 62, 207.
Y. Matsuya, K. Sasaki, M. Nagaoka, H. Kakuda, N. Toyooka, N. Imanishi, H. Ochiai, and H.

HETEROCYCLES, Vol. 88, No. 1, 2014
763
Nemoto, J. Org. Chem., 2004, 69, 7989.
D.-Y. Yu, Y. Matsuya, Q.-L. Zhao, K. Ahmad, Z.-L. Wei, H. Nemoto, and T. Kondo, Apoptosis, 2007,
2, 1523.
5
.
.
1
6
(a) Y. Matsuya, K. Sasaki, H. Ochiai, and H. Nemoto, Bioorg. Med. Chem., 2007, 15, 424; (b) Y.
Matsuya, N. Suzuki, S. Kobayashi, T. Miyahara, H. Ochiai, and H. Nemoto, Bioorg. Med. Chem.,
2
010, 18, 1477.
7
8
9
.
.
.
K. Sugimoto, K. Tamura, N. Ohta, C. Tohda, N. Toyooka, H. Nemoto, and Y. Matsuya, Bioorg. Med.
Chem. Lett., 2012, 22, 449.
K. Sugimoto, K. Tamura, C. Tohda, N. Toyooka, H. Nemoto, and Y. Matsuya, Bioorg. Med. Chem.,
2
013, 21, 4459.
Several palladium-catalyzed reactions were examined, however, no corresponding products were
observed and starting materials were recovered.
1
1
0. A. Klapars, X. Huang, and S. L. Buchwald, J. Am. Chem. Soc., 2002, 124, 7421.
1. J. T. Markiewicz, O. Wiest, and P. Helquist, J. Org. Chem., 2010, 75, 4887.