Iridium-catalyzed C-H borylation-based synthesis of natural indolequinones

Article abstract of DOI:10.1021/jo300330u

An iridium-catalyzed C-H borylation provides the key step in a short synthesis of two indolequinone natural products. This regioselective C-H functionalization strategy delivers 7-borylindoles that undergo facile oxidation-hydrolysis to 7-hydroxyindoles and subsequent oxidation to the desired indolequinones, thereby demonstrating a powerful application of the iridium-catalyzed C-H borylation reaction. A significant result has arisen from the iridium-catalyzed borylation of N-diethylhydrosilyl-6-methoxyindole; even in the presence of a substituent at C6, the N-hydrosilyl group still directs borylation exclusively into the more sterically hindered C7 position in preference to C2.

Full text of DOI:10.1021/jo300330u

Brief Communication
pubs.acs.org/joc
Iridium-Catalyzed C−H Borylation-Based Synthesis of Natural
Indolequinones
Christy Wang and Jonathan Sperry*
School of Chemical Sciences, University of Auckland, 23 Symonds Street, Auckland, New Zealand
*
S Supporting Information
ABSTRACT: An iridium-catalyzed C−H borylation provides
the key step in a short synthesis of two indolequinone natural
products. This regioselective C−H functionalization strategy
delivers 7-borylindoles that undergo facile oxidation−hydrol-
ysis to 7-hydroxyindoles and subsequent oxidation to the
desired indolequinones, thereby demonstrating a powerful
application of the iridium-catalyzed C−H borylation reaction.
A significant result has arisen from the iridium-catalyzed borylation of N-diethylhydrosilyl-6-methoxyindole; even in the presence
of a substituent at C6, the N-hydrosilyl group still directs borylation exclusively into the more sterically hindered C7 position in
preference to C2.
he widespread interest in compounds bearing the
indolequinone pharmacophore began with the discovery
changes in the substrates, resulting in narrow scope that can
inhibit the efficient production of structurally diverse analogues,
a particularly important requirement in medicinal chemistry
settings. The synthesis of indolequinones by a late-stage indole
functionalization approach has the potential to circumvent
these shortcomings but would require the selective manipu-
lation of the benzo-fused aromatic ring of indole, a far from
straightforward task when considering the greater reactivity of
T
of the archetypal quinone bioreductive anticancer agent
mitomycin C (MMC, 1), a natural product in clinical practice
since the 1970s for the treatment of breast, stomach, esophagus,
1
−3
and bladder tumors.
Another notable example is the MMC
analogue apaziquone (E09, 2), currently in the advanced stage4s
of clinical trials for the treatment of superficial bladder cancer.
Other natural indolequinones with interesting biologica5l
activities include the topoisomerase II inhibitor BE-10988 3
11
the azole ring. Indeed, a review of the literature reveals that
the majority of existing methods that functionalize the benzo-
fused moiety of the indole ring in preparation for
indolequinone synthesis require the azole ring to be substituted
6
and the antimicrobial indolequinones 4 and 5 (Figure 1).
1
0,12−14
in order to avoid unwanted reactions at this site.
In the
context of indolequinone synthesis, existing methods that can
be used to selectively functionalize the benzo-fused moiety of
indole in the presence of an unsubstituted azole ring are not
ideal. The regioselective oxidation (C4) of the indole ring can
be achieved but is highly substrate specific and requires the use
of toxic thallium salts. The resulting 4-hydroxyindoles then
15
undergo facile oxidation to the desired indolequinones. The
direct oxidation of indoles to indolequinones can be effected
with Dess−Martin periodinane but is restricted to indoles
bearing a benzylamide at C5 and the indole nitrogen must be
16
alkylated. Also, the direct electrochemical oxidation of 5-
hydroxytryptamine leads directly to the corresponding
indolequinone. Because of the limited substrate scope of
Figure 1. Biologically active indolequinones.
17
the methods outlined in the above, a novel procedure for the
late-stage functionalization−oxidation of indole that would
constitute a new approach to indolequinones was sought.
Herein, we report our initial efforts toward this goal that has
culminated in the efficient synthesis of two indolequinone
natural products. A striking result obtained from the iridium-
As part of an ongoing project aimed at the synthesis of
natural indolequinones, we desired a procedure that would
7
provide indolequinones directly from the parent indole, thereby
avoiding commonly employed fragment-based approaches to
indolequinones that typically rely on the stepwise construction
of an amino- or hydroxyindole followed by oxidation to the
8
9,10
indolequinone or the annulation of a substituted quinone.
These methods are often lengthy and sensitive to structural
Received: February 15, 2012
Published: March 2, 2012
©
2012 American Chemical Society
2584
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The Journal of Organic Chemistry
Brief Communication
catalyzed C−H borylation of a 6-substituted indole is also
discussed.
Scheme 2. Synthesis of Indolequinone Natural Product 4
A particularly fascinating area of C−H functionalization is the
recently discovered iridium-catalyzed C−H borylation of
1
8
indole, a reaction that was initially only selective for C7
when a substituent at C2 was present to block reactivity at this
1
9
site. In a landmark recent development, Hartwig and co-
workers demonstrated that N-hydrosilylindoles undergo
borylation exclusively at C7 even in the absence of a substituent
20
at C2, vastly increasing the scope of this process. Inspired by
these recent advances, we set out to apply this C−H borylation
methodology as the basis for a novel approach to
indolequinones and chose to target the relatively simple natural
products 4 and 5 to gauge the viability of this proposal
(
Scheme 1). It was envisaged commercially available methox-
Scheme 1. Synthetic Plan
approach to indolequinones based on a late-stage indole
functionalization.
With the synthesis of the natural product 4 successful, we set
out to extend this methodology to the synthesis of the
indolequinone natural product 5 (Scheme 3). Upon subjecting
Scheme 3. Synthesis of Indolequinone Natural Product 5
yindoles 6 and 7 would undergo iridium-catalyzed C−H
borylation to their respective 7-borylindoles 8 and 9 that upon
oxidation−hydrolysis would furnish 7-hydroxyindoles 10 and
11; 7-hydroxyindoles are themselves highly useful and sought
after synthetic intermediates that often require lengthy and/or
2
1,22
poor yielding routes for their preparation.
The oxidation of
7
-hydroxyindoles 10/11 would then provide the natural
indolequinones 4 and 5. At the outset of this project it was
evident that there were no literature examples reporting the
18−20
iridium-catalyzed borylation of a 6-substituted indole;
therefore, obtaining the desired regioisomer (9) from the
borylation of 6-methoxyindole 7 was not guaranteed.
6
-methoxyindole 7 to the same C−H borylation conditions
1
The natural product 4 was the initial target which could be
traced back to commercially available 5-methoxyindole. Thus,
indole 6 was subjected to an uneventful one-pot hydro-
silylation, iridium-catalyzed borylation, and desilylation accord-
described for the preparation of regioisomer 8, TLC and H
NMR analysis of the reaction mixture indicated the formation
of single borylindole regioisomer. We were confident from 2D
24
20
NMR experiments that the regioisomer was indeed the
ing to the reported procedure, affording 5-methoxy-7-
2
0
desired 7-borylindole 9, but this was pleasingly confirmed upon6
its oxidation-hydrolysis to the known 6-methoxyindol-7-ol 11.
Although it is well-established that N-hydrosilylindoles undergo
iridium-catalyzed borylation exclusively at C7 even in the
absence of a substituent at C2, this example demonstrates
that the remarkable regiochemical outcome is still observed
even in the presence of a substituent at C6. The moderate yield
observed in the borylation of 7 to 9 was not due to incomplete
borylation, but attributed to protodeborylation during the
cleavage of the hydrosilyl group, a phenomenon previously
borylindole 8, whereupon the boronate oxidation−hydrolysis
was considered. Examples reporting the oxidation−hydrolysis
23
of borylindoles to hydroxyindoles in the literature are scarce,
but it was found that treatment of 8 with hydrogen peroxide
and sodium hydroxide in THF at 0 °C gratifyingly gave 5-
methoxyindol-7-ol 10 after 10 min in excellent yield. Finally,
salcomine-catalyzed oxidation of 10 gave the indolequinone 4
20
6
,24
which was identical in all aspects to the natural product
Scheme 2). The synthesis of the natural product 4 described
(
herein required three steps from commercially available 5-
methoxyindole, compared to the single literature synthesis that
20
reported. Oxidation of 10 with salcomine then delivered the
indolequinone 5, the spectroscopic data of which was in full
agreement with the natural product (Scheme 3). The
6
required seven steps. More importantly, the successful
24
synthesis of 4 from 5-methoxyindole 6 constitutes a novel
2
585
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The Journal of Organic Chemistry
Brief Communication
synthesis of 5 described herein is significantly shorter than the
existing methods.
the title compound as an orange oil [90 mg, 0.33 mmol, 66%, (91%
6
,10,25
brsm)]: δ (400 MHz, CDCl ) 9.14 (1 H, br s, NH), 7.36 (1 H, d, J
H
3
2
.8, Ar-H), 7.31 (1 H, d, J 2.0, Ar-H), 7.27 (1 H, t, J 2.0, H-2), 6.51 (1
H, dd, J 2.0, 2.8, H-3), 3.90 (3 H, s, Me), 1.42 (12 H, s, 4 × Me); δC
100 MHz, CDCl ) 154.1 (C), 136.8 (C), 127.9 (C), 125.2 (CH),
In conclusion, we have reported the short synthesis of two
indolequinone natural products that was enabled by an iridium-
catalyzed C−H borylation. It has also been discovered that even
in the presence of a substituent at C6, the C−H borylation of
N-diethylhydrosilyl-6-methoxyindole still occurs regioselec-
tively at the more sterically hindered C7 position in preference
to C2. This late-stage functionalization approach to indolequi-
nones should allow for the modular introduction of different
substituents and functional groups onto the indole substrates,
facilitating the production of a diverse series of indolequinone
analogues. This approach also describes a potentially useful
synthesis of 7-hydroxyindoles. The scope and utility of this
methodology with a variety of indoles, related heterocycles and
in natural product synthesis, together with its application in
large scale settings, is currently under investigation.
(
3
1
18.1 (CH), 107.9 (CH), 101.8 (CH), 84.2 (2 × C), 56.5 (Me), 25.3
(4 × Me), 1 × C not observed. Spectroscopic data consistent with
20
literature values.
-Methoxy-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indole
6
(9). From 6-methoxyindole 7: Purification by flash-column chroma-
tography on silica gel eluting with n-hexanes−ethyl acetate (9:1) gave
the title compound as an orange solid [34 mg, 0.12 mmol, 25%, (46%
−
1
brsm)]; mp 91.5−96.6 °C; ν (neat)/cm 3406, 2978, 2929, 1859,
max
1
1
601, 1585, 1537, 1507, 1497, 1459, 1430, 1380, 1338, 1299, 1238,
202, 1168, 1135, 979, 878, 856; δ (400 MHz, CDCl ) 9.39 (1 H, br
H
3
s, NH), 7.68 (1 H, d, J 8.4, Ar-H), 7.16 (1 H, dd, J 5.3, 2.4, H-2), 6.80
1 H, d, J 8.4, Ar-H), 6.46 (1 H, dd, J 5.3, 2.0, H-3), 3.91 (3 H, s, Me),
.41 (12 H, s, 4 × Me); δ (100 MHz, CDCl ) 162.5 (C), 142.4 (C),
(
1
C
3
124.9 (CH), 123.4 (CH), 122.0 (C), 106.2 (CH), 101.6 (CH), 83.2 (2
C), 57.6 (Me), 25.0 (4 × Me), 1 × C not observed; m/z (ESI) 296
×
+
+
EXPERIMENTAL SECTION
[100, (M + Na) ], 226 (4), 134 (5); HRMS [ESI, (M + Na) ] found
■
+
2
96.1440, [C H BNO + Na] requires 296.1431.
15 20 3
General Experimental Details. Commercially available reagents
were used throughout without purification unless otherwise stated.
Anhydrous solvents were used as supplied. Tetrahydrofuran was
distilled from sodium benzophenone ketyl under nitrogen atmosphere.
Dichloromethane was distilled from calcium hydride under a nitrogen
atmosphere. Ether refers to diethyl ether. Reactions were routinely
carried out under a nitrogen or argon atmosphere. Analytical thin-layer
chromatography was carried out on aluminum backed plates coated
with silica gel and visualized under UV light at 254 and/or 360 nm
and/or potassium permanganate or ethanolic vanillin dip. Chromatog-
raphy was carried out on silica gel. Fully characterized compounds
were chromatographically homogeneous. Infrared spectra were
Procedure for Boronate Oxidation-Hydrolysis. A solution of
indole 8 or 9 (30 mg, 0.11 mmol) in THF (3 mL) was cooled to 0 °C.
Hydrogen peroxide (30% in H O, 0.1 mL) and sodium hydroxide (1
2
M, 0.1 mL) were added, and the reaction mixture was stirred at 0 °C
for 10 min. Ether (20 mL) was added, and the organic layer was
removed, washed with water (8 mL) and brine (8 mL), dried
(
Na SO ), filtered, and concentrated in vacuo. Purification by flash-
2 4
column chromatography gave the 7-hydroxyindole product 10 or 11.
-Methoxyindol-7-ol (10). From borylindole 8: Purification by
5
flash-column chromatography on silica gel using n-hexanes−ethyl
acetate (1:1) as eluent gave the title compound (14.4 mg, 0.087 mmol,
−1
−1
80%) as an orange oil: νmax (neat)/cm 3410, 3292, 2965, 1714, 1649,
recorded on an FT-IR spectrometer in the range 4000−600 cm .
NMR spectra were recorded on a 400 MHz ( H frequency)
1
1589, 1530, 1426, 1289, 1240, 1135, 1032, 821, 757; δH (400 MHz,
DMSO-d ) 10.68 (1 H, br s, NH), 9.56 (1 H, s, OH), 7.14 (1 H, t, J
spectrometer. Chemical shifts are quoted in ppm and J values in Hz.
Chemical shift values are referenced against residual proton in the
deuterated solvents. Assignments were made with the aid of DEPT
6
2
.8, H-2), 6.48 (1 H, d, J 2.0, Ar-H), 6.25 (1 H, t, J 2.8, H-3), 6.16 (1
H, d, J 2.0, Ar-H), 3.68 (3 H, s, Me); δ (100 MHz, DMSO-d ) 153.9
C
6
13
(C), 143.8 (C), 129.0 (C), 124.8 (CH), 121.4 (C), 101.3 (CH), 96.3
135, COSY, NOESY, HSQC and HMBC experiments. In the
C
+
(
CH), 92.4 (CH), 55.1 (Me); m/z (ESI) 186 [100, (M + Na) ];
NMR spectra, signals corresponding to CH, CH , or CH are assigned
2
3
+
+
HRMS [ESI, (M + Na) ] found 186.0519, [C H NO + Na] requires
from DEPT-90 and -135 spectra; all others are quaternary C. Mass
spectra were recorded on a time-of-flight mass spectrometer using
electrospray ionization (ESI).
9
9
2
1
86.0525.
6
-Methoxyindol-7-ol (11). From borylindole 9: Purification by
flash-column chromatography on silica gel using n-hexanes−ethyl
acetate (1:1) as eluent gave the title compound (15.7 mg, 0.096 mmol,
Procedure for C−H Borylation. In a Pyrex sealed tube with a
stirring bar and Teflon-lined screwcap were added [Ru(p-cymene)-
Cl ] (3 mg, 0.005 mmol, 1 mol %), methoxyindole 6 or 7 (74 mg, 0.5
9
7
5
6%) as an orange oil; δ (400 MHz, CDCl ) 8.21 (1 H, br s, NH),
H 3
2
2
.13 (2 H, m, Ar-H, H-2), 6.84 (1 H, d, J 8.5, Ar-H), 6.19 (1 H, dd, J
mmol), diethylsilane (0.14 mL, 1 mmol), and degassed toluene (0.5
mL), and the resulting mixture was heated to 90 °C for 15 h under a
blanket of argon. After being cooled to room temperature, the mixture
was transferred to a round bottomed flask, and volatile materials were
removed under reduced pressure to give the N-hydrosilylindole (0.5
mmol). A catalyst solution was prepared by adding [Ir(OMe)COD]2
1
.3, 2.3, H-3), 5.65 (1 H, br s, OH), 3.93 (3 H, s, Me); H NMR data
6
consistent with that reported in the literature but due to incomplete
literature characterization, full spectroscopic data was obtained; ν
max
−1
(neat)/cm 3188, 2921, 2852, 1728, 1610, 1557, 1422, 1384, 1199,
1
052, 894, 789; δ (400 MHz, DMSO-d ) 10.72 (1 H, br s, NH), 8.78
H
6
(1 H, s, OH), 7.13 (1 H, t, J 2.6, H-2), 6.91 (1 H, d, J 8.6, Ar-H), 6.75
(
0
10 mg, 0.015 mmol, 6 mol %) and 4,4′-di-tert-butylbipyridine (8 mg,
.03 mmol, 12 mol %) in THF (0.5 mL) followed by the addition of
(1 H, d, J 8.6, Ar-H), 6.27 (1 H, dd, J 3.2, 2.6, H-3), 3.78 (3 H, s, Me);
δ (100 MHz, DMSO-d ) 141.2 (C), 132.5 (C), 127.2 (C), 124.6 (C),
bis(pinacolato)diboron (190 mg, 0.75 mmol) and pinacolborane (0.01
mL, 0.07 mmol, 14 mol %) with stirring for 1 min. The resulting deep-
red solution was transferred to the round bottomed flask containing
the N-hydrosilylindole (0.5 mmol) in THF (1 mL) and the whole
reaction mixture immediately transferred to a sealed tube and heated
to 85 °C for 15 h under a blanket of argon. Upon cooling to room
temperature, sodium acetate (3 M, 0.25 mL) was added and the
reaction mixture was stirred at room temperature for 2 h. The reaction
mixture was diluted with ether (20 mL) and water (20 mL). The
aqueous layer was separated and washed with ether (2 × 15 mL), and
the combined organic phases were washed with brine (30 mL), dried
C
6
1
24.5 (CH), 110.1 (CH), 108.6 (CH), 101.0 (CH), 57.9 (Me); m/z
+
+
(ESI) 186 [100, (M + Na) ]; HRMS [ESI, (M + Na) ] found
+
1
86.0529, [C H NO + Na] requires 186.0525.
9 9 2
Indolequinone Oxidation. 5-Methoxyindole-4,7-quinone (4).
To a solution of indole 10 (10 mg, 0.061 mmol) in acetonitrile
3 mL) was added salcomine (2.38 mg, 0.007 mmol, 12 mol
(
%), and the reaction mixture was stirred at room temperature
under an atmosphere of oxygen for 4 h. Silica gel (∼30 mg) was
added and the solvent concentrated in vacuo. The dry silica gel
residue which was purified by flash chromatography on silica
gel using n-hexanes−ethyl acetate (1:1) as eluent to give the
title compound (8.1 mg, 0.045 mmol, 75%) as a bright yellow
(
Na SO ), filtered, and concentrated in vacuo. Purification gave the
2 4
borylindole product 8 or 9.
-Methoxy-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indole
8). From 5-methoxyindole 6: Purification by flash-column chroma-
tography on silica gel eluting with n-hexanes−ethyl acetate (3:1) gave
6
5
solid: mp 198−200 °C (lit. mp 198−200 °C); νmax (neat)/
cm 3363, 3230, 2850, 1673, 1589, 1496, 1402, 1247, 1124,
−1
(
1084, 927, 807, 748; δ (400 MHz, DMSO-d ) 12.63 (1 H, br
H
6
2
586
dx.doi.org/10.1021/jo300330u | J. Org. Chem. 2012, 77, 2584−2587

The Journal of Organic Chemistry
Brief Communication
s, NH), 7.15 (1 H, d, J 2.6, H-2), 6.52 (1 H, d, J 2.6, H-3), 5.82
(
́
(10) For complementary fragment based approaches, see: Saa, J. M.;
1 H, s, H-6), 3.78 (3 H, s, Me); δ (100 MHz, DMSO-d )
C
Marti, C.; Raso-García, A. J. Org. Chem. 1992, 57, 589−594 and
references therein.
6
1
77.9 (CO), 176.7 (CO), 160.6 (C), 131.4 (C), 125.6
(
CH), 122.9 (C), 107.3 (CH), 106.1 (CH), 56.6 (Me); m/z
ESI) 200 [100, (M + Na) ], 176 (35), 167 (40), 156 (23);
(11) Bandini, M.; Eichholzer, A. Angew. Chem., Int. Ed. 2009, 48,
9608−9644.
+
(
HRMS [ESI, (M + Na) ] found 200.0323. [C H NO + Na]
+
+
9
requires 200.0318. Spectroscopic data consistent with literature
7
3
(12) Nitration−reduction: Natasuka, S.-I.; Ueda, K.; Asano, O.; Goto,
T. Heterocycles 1987, 26, 65−68.
6
values.
(13) Hydroxyindole oxidation then Thiele−Winter acetoxylation or
reductive alkylation: Allen, G. R. Jr.; Poletto, J. F.; Weiss, M. J. J. Am.
Chem. Soc. 1964, 86, 3877−3878.
6
-Methoxyindole-4,7-quinone (5). To a solution of indole 11 (8
mg, 0.049 mmol) in dimethylformamide (3 mL) at 0 °C was added
salcomine (2 mg, 0.006 mmol, 12 mol %), and the reaction mixture
was stirred at room temperature under an atmosphere of oxygen for 2
h. The reaction mixture was diluted with ethyl acetate (20 mL) and
water (10 mL), the organic phase removed, and the aqueous layer
extracted with ethyl acetate (15 mL). The combined organic phases
were dried (Na SO ), filtered, and concentrated in vacuo. Purification
(14) Dakin oxidation: Alamgir, M.; Mitchell, P. S. R.; Bowyer, P. K.;
Kumar, N.; Black, D. StC. Tetrahedron 2008, 64, 7136−7142.
(15) Carr, G.; Chung, M. K. W.; Mauk, A. G.; Andersen, R. J. J. Med.
Chem. 2008, 51, 2634−2637.
(
16) Nicolaou, K. C.; Sugita, K.; Baran, P. S.; Zhong, Y.-L. J. Am.
Chem. Soc. 2002, 10, 2221−2232.
17) Wrona, M. Z.; Lemordant, D.; Lin, L.; Blank, C. L.; Dryhurst, G.
2
4
by flash chromatography on silica gel eluting with n-hexanes−ethyl
(
acetate (1:1) gave the title compound (4.2 mg, 0.024 mmol, 50%) as a
J. Med. Chem. 1986, 29, 499−505.
6
bright orange solid: mp 186−189 °C (lit. mp 188−190 °C); ν
max
(18) Ishiyama, T.; Takagi, J.; Hartwig, J. F.; Miyaura, N. Angew.
Chem., Int. Ed. 2002, 41, 3056−3058.
−1
(
neat)/cm 3184, 2924, 2854, 1726, 1667, 1634, 1586, 1539, 1494,
1
403, 1331, 1283, 1193, 1093, 922, 887, 797; δ (400 MHz, DMSO-
H
(19) Sulanga, P.; Chotana, G. A.; Holmes, D.; Reichle, R. C.;
Maleczka, R. E. Jr.; Smith, M. R. III J. Am. Chem. Soc. 2006, 128,
15552−15553.
d6) 12.74 (1 H, br s, NH), 7.25 (1 H, d, J 2.4, H-2), 6.47 (1 H, d, J 2.4,
H-3), 5.80 (1 H, s, H-5), 3.76 (3 H, s, Me); δ (100 MHz, DMSO-d )
C
6
1
82.9 (CO), 170.7 (CO), 159.7 (C), 129.1 (C), 127.5 (CH),
(20) Robbins, D. W.; Boebel, T. A.; Hartwig, J. F. J. Am. Chem. Soc.
1
26.0 (C), 107.1 (CH), 106.9 (CH), 56.3 (Me). m/z (ESI) 200
2
010, 132, 4068−4069 The directed C−H borylation reaction was
+
+
[
[
100%, (M + Na) ]; HRMS [ESI, (M + Na) ] found 200.0318,
C H NO + Na] requires 200.0318. Spectroscopic data consistent
only conducted on indoles with substituents at the 3-, 4-, and 5-
+
9
7
3
positions..
6,25
with literature values.
(21) Dalpozzo, R.; Bartoli, G. Curr. Org. Chem. 2005, 9, 163−178.
(22) Charrier, N.; Demont, E.; Dunsdon, R.; Maile, G.; Naylor, A.;
ASSOCIATED CONTENT
O’Brien, A.; Redshaw, S.; Theobald, P.; Vesey, D.; Walter, D. Synlett
005, 3071−3074 and references therein..
23) Hartung, C. G.; Fecher, A.; Chapell, B.; Snieckus, V. Org. Lett.
■
2
(
*
S
Supporting Information
1
H and 13C NMR spectra of all compounds and 2D NMR
2003, 5, 1899−1902.
spectra of 9. This material is available free of charge via the
Internet at http://pubs.acs.org.
(24) See Supporting Information for relevant spectra.
(25) Jackson, Y. A.; Billimoria, A. D.; Sadanandan, E. V.; Cava, M. P.
J. Org. Chem. 1995, 60, 3543−3545.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: j.sperry@auckland.ac.nz.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Royal Society of New Zealand Marsden fund for
financial support.
REFERENCES
■
(
1) Carter, S. K.; Crooke, S. T. Mitomycin C: Current Status and New
Developments; Academic Press: New York, 1979.
(
2) Seow, H.; Penketh, P. G.; Baumann, R. P.; Sartorelli, A. C.
Methods Enzymol. 2004, 382, 221−233.
3) Alcain, F. J.; Villalba, J. M. Expert Opin. Ther. Pat. 2007, 17, 649−
65.
4) Jain, A.; Phillips, R. M.; Scally, A. J.; Lenaz, G.; Beer, M.; Puri, R.
Urology 2009, 73, 1083−1086.
5) Oka, H.; Yoshinari, T.; Murai, T.; Kuwamura, K.; Satoh, F.;
Funaishi, K.; Okura, A.; Suda, H.; Okanishi, M.; Shizuri, Y. J. Antibiot.
991, 44, 486−491.
6) Fukuyama, Y.; Iwatsuki, C.; Kodama, M.; Ochi, M.; Kataoka, K.;
(
6
(
(
1
(
Shibata, K. Tetrahedron 1998, 54, 10007−10016.
(
(
7) Wang, C.; Sperry, J. Org. Lett. 2011, 13, 6444−6447.
8) For a representative example, see: Nobuhiro, J.; Hirayama, M.;
Choshi, T.; Kamoshita, K.; Maruyama, S.; Sukenaga, Y.; Ishizu, T.;
Fujioka, H.; Hibino, S. Heterocycles 2006, 70, 491−499.
(
9) For a representative example, see: Inman, M.; Moody, C. J. J. Org.
Chem. 2010, 75, 6023−6026 and references therein..
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587
dx.doi.org/10.1021/jo300330u | J. Org. Chem. 2012, 77, 2584−2587