Stereospecificity in Intramolecular Photoredox Reactions of Naphthoquinones: Enantioselective Total Synthesis of (?)-Spiroxin C

Article abstract of DOI:10.1002/anie.201705562

Intramolecular photoredox reactions of naphthoquinone derivatives were found to proceed in a stereospecific manner. This method was used as a basis for the enantioselective total synthesis of (?)-spiroxin C.

Full text of DOI:10.1002/anie.201705562

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Accepted Article
Title: Stereospecificity in Intramolecular Photoredox Reactions of
Naphthoquinones: Enantioselective Total Synthesis of (-)-
Spiroxin C
Authors: Yoshio Ando, Atsuko Hanaki, Ryota Sasaki, Ken Ohmori, and
Keisuke Suzuki
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201705562
Angew. Chem. 10.1002/ange.201705562
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10.1002/anie.201705562
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Stereospecificity in Intramolecular Photoredox Reactions of
Naphthoquinones: Enantioselective Total Synthesis of (–)-
Spiroxin C
Yoshio Ando, Atsuko Hanaki, Ryota Sasaki, Ken Ohmori, and Keisuke Suzuki*
In memory of Takao Ikariya
Abstract: Intramolecular photoredox reactions of naphthoquinone
Scheme 1. Photoredox reaction and a stereochemical question.
derivatives were shown to proceed in a stereospecific manner, by
which the first enantioselective total synthesis of (–)-spiroxin C has
been achieved.
Is the reaction stereospecific? – which could be addressed by
using substrates A with a stereogenic center at the benzylic
Previously
naphthoquinone derivatives (Scheme 1).[1] Upon ambient light
irradiation, naphthoquinones undergo an intramolecular
we
reported
a
photoredox
reaction
of
position (asterisked). We investigated this question in the
context of the total synthesis of spiroxin C (1), one of the
members of a class of marine antibiotics (Figure 1).[3] It could be
regarded as a naphthoquinone dimer, and the twenty carbon-
atom framework with dense oxygen functionalities constitutes a
complex hexacyclic structure with six stereogenic centers,
posing intriguing challenges for chemical synthesis. Although
such unusual structural features as well as potential bioactivity
attracted attention of the synthetic community,[4,5] Imanishi’s
work on rac-1 is the only example of the completed synthesis.[4]
Critical to our synthetic planning was the stereochemical course
of the photoredox reaction of naphthoquinone III, which would
hopefully proceed in a stereospecific manner. If viable, spiro-
ether IV would be available in a stereo-defined form, bearing the
C-4’ quaternary center in 1.
I
photoredox reaction to give oxacycle II, where the benzylic
oxidation level is increased and the quinone is reduced. The
mechanism was assumed to follow Norrish-type II intramolecular
1,5-hydrogen shift to form diradical C and subsequent electron
transfer to zwitterion D that undergoes oxycyclization to form
product E.[1] Aside from some reports on the biosynthetic
implications,[2] such a photoredox process of quinones has been
overlooked and never been exploited in organic synthesis.
However, we recognized a great potential of the process,
particularly if the following stereochemical question were
positively answered.
O
O
OH
hν
OH
O
reduced
oxidized
RO
O
RO
OH
9
photoredox
reaction
1
4
R
R'
R
R'
O
O
H
hν
6
O
O
O
I
II
stereochemistry?
*
4'
*
H
O
OR
O
OR
4'
1'
6'
*
O
O
O
O
O
O
O
Norrish
type II
9'
hν
III
IV
(1,5-shift)
(–)-spiroxin C (1)
*
*
H
O
O
H
H
Figure 1. (–)-Spiroxin C and the stereochemical question.
A
B
C
O–
OH
O
electron
transfer
In this communication, we wish to describe an affirmative
answer to this scenario, achieving the first enantioselective total
synthesis of (–)-spiroxin C (1).
cyclization
*
O
H
As initial model compounds, we prepared a diastereomeric pair
of naphthoquinones 2 and 4 (cis and trans,[6] racemate),[7] which
were subjected to the photoredox reaction (Scheme 2). We were
pleased to find that, upon exposure to fluorescent light (CH3CN,
RT, 8 h), the cis-isomer 2 was converted to spiroether 3 in
excellent stereoisomeric purity (3:5 = 98:2).[8] Under the same
conditions, the trans-isomer 4 was converted to the isomeric
E
D
[*]
Dr. Y. Ando, A. Hanaki, R. Sasaki, Prof. Dr. K. Ohmori, Prof. Dr. K.
Suzuki
Department of Chemistry, Tokyo Institute of Technology
2-12-1 O-okayama, Meguro, Tokyo 152-8551 (Japan)
E-mail: ksuzuki@chem.titech.ac.jp
spiroether
5 (3:5 =
3:97).[8] Thus, these photoreactions
proceeded in almost complete stereospecificity. The structures
of 3 and 5 were assigned by NOE correlations,[7] proving that the
photochemical reaction occurred in a retentive manner: the
Supporting information for this article is given via a link at the end of
the document.
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10.1002/anie.201705562
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benzylic C–H bonds in 2 and 4 were replaced by a C–O bond
with retention of the configuration, respectively.
In the case of systems with less steric hindrance, the C–C bond
rotation would become easier, and corrosion of the
sterechemical integrity may begin. Thus, we prepared seemingly
more challenging model substrates, a set of naphthoquinones 6
and 8 possessing a 1,3-disubstituted cyclohexane ring with cis
and trans substituents[6] (Scheme 4). Pleasingly, the photoredox
reactions of 6 and 8 (fluorescent light, CH3CN, RT, 8 h) again
proceeded smoothly, giving spiroethers 7 and 9 with virtually
MeO
OH
O
MeO
O
O
hν
CH3CN
RT
H
complete retention of the stereochemistry (d.r.
= 99:1),
86%
TBSO
TBSO
respectively.[8] The stereochemical assignments of 7 and 9 were
based on the NOE correlations, respectively. Note that the
cyclohexyl ring in 9 was flipped as shown.
2
3
(cis)
(3:5 = 98:2)
MeO
OH
MeO
O
O
MeO
O
key NOE correlations
MeO
OH
MeO
OH
O
hν
hv
H
O
CH3CN
RT
CH3CN
RT
O
O
H
H
TBSO
TBSO
81%
88%
H
H
OAc
OAc
4
5
H
6
(cis)
7
H
(trans)
(3:5 = 3:97)
OAc
(7:9 = 99:1)
MeO OH
7
MeO
O
O
Scheme 2. Stereospecific photoredox reactions-1.
MeO
OH
O
hv
CH3CN
RT
H
H
Scheme
3 shows a rationale for these pleasing results.
O
H
H
Regardless of the preferred ground state conformation, the initial
hydrogen abstraction in the excited state must occur within a
conformation similar to F, where the benzylic hydrogen is
allocated near the excited quinone carbonyl. The retentive
nature of the process is explained by assuming rapid following
events, i.e., (1) the electron transfer from biradical G to generate
zwitterion H, and (2) the cyclization of H to give oxacycle I. In
other words, although the central chirality is lost after the
hydrogen abstraction, the chiral information is preserved as an
axial chirality[9] in the intermediary radical G and the cation H,
thanks to scaffold a reminiscent of biaryl compounds.[10]
OAc
94%
OAc
OAc
8
(trans)
9
(7:9 = 1:99)
9
Scheme 4. Stereospecific photoredox reactions-2.
With these promising results in hand, we proceeded to plan the
total synthesis of 1. Our retrosynthetic analysis is shown in
Scheme 5. Two oxirane rings in 1 could be derived from bis-
enone 10 by two-fold epoxidation, for which we could expect
O–
MeO
MeO
O
good stereoselectivities, learning from the
O
MeO
MeO
OH
synthesis.[4] As the precursor for bis-
electron
transfer
enone 10, spiroether 11 was envisaged,
hν
cyclization
O
O
+
HO
H
O
assuming that one of the enones
(highlighted in red) would be constructed
by an oxidative spiro-acetal formation,
while the other (highlighted in blue) was
retrosynthetically reduced to a saturated
alcohol. The key was use of the C-1’
stereogenic center as the basis for the
absolute stereocontrol as will be
discussed later.
H
(1,5-H)
fast
fast
F
H
I
G
retention
slow
slow
slow
slow
MeO
O–
MeO
MeO
OH
O
Assuming the retentive nature of the key
photoredox reaction, oxacycle 11 could be
traced back to naphthoquinone 12 with the
(R)-stereogenic center at C-4’, which
could be induced by the hydrogenation of
+
O
HO
HO
J
K
L
inversion
alkene 13. The hope was a high diastereofacial discrimination
during the hydrogenation by the influence of the stereogenic
center at C-1’. Final dissection suggested a set of starting
materials, bromonaphthalene 14[1] and enantio-enriched
tetralone 15. The C-1’ stereogenic center in 15 could be
Scheme 3. Rationale for the stereospecificity.
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Scheme 6. Synthesis of tetralone (R)-15. a) BnBr, K2CO3, DMF, RT, 2.5 h; b)
RuCl(p-cymene)[(R,R)-Ts-DPEN] (1 mol%), formic acid, triethylamine, RT, 42
h, 89%, >99% ee (2 steps); c) acetic anhydride, pyridine, 4-DMAP, CH2Cl2, 2.5
h; d) Ce(NH4)2(NO3)6, CH3CN, H2O, 0 °C, 1.5 h; e) TPAP, 4-methylmorpholine
N-oxide, molecular sieves 4A, CH2Cl2, RT, 3 h; f) LiOH·H2O, THF, H2O, 50 °C,
10 h; g) TBSCl, imidazole, DMF, 18 h, 65% (5 steps). Bn = benzyl, (R,R)-Ts-
DPEN = (1R,2R)-N-p-toluenesulfonyl-1,2-diphenylethylenediamine, 4-DMAP =
N,N-dimethyl-4-aminopyridine, TPAP = tetrapropylammonium perruthenate,
TBS = tert-butyldimethylsilyl.
established by the enantioselective reduction of the
corresponding carbonyl compound.
Three synthetic challenges en route to
1
were, (1)
enantioselective synthesis of naphthoquinone 12 as the
substrate for the key photoreaction, (2) viability and
stereospecificity of the photoreaction to such functionalized
substrate 12, and (3) construction of the highly oxygenated
polycyclic structure.
Two building blocks 14[1] and (R)-15 were combined (Scheme 7).
A solution of tetralone (R)-15 and LaCl3·2LiCl[15] in a mixed
solvent (THF, Et2O, v/v = 2/1) was added to a solution of the
aryllithium derived from 14 (sBuLi, THF, Et2O, 0 °C, 15 min). The
crude adduct 21 was treated with silica gel[16] in dichloromethane
(RT, 19 h), where dehydration occurred to give styrene 13 in
85% yield in two steps. It should be noted that styrene 13 was
labile under acidic conditions (e.g. a trace acid in CDCl3), easily
aromatized to give the corresponding bis-naphthalene. Catalytic
hydrogenation of 13 (H2, 10% Pd/C, THF, MeOH, 12 h)
saturated the C=C bond and also cleaved the benzyl protection
to give a quantitative yield of phenol 22 as an inseparable
mixture of diastereomers (ratio 14:1, 1H NMR assay).[7] The
relative stereochemistry of the major isomer was determined as
cis by the NOE correlation between the 1’- and 4’-hydrogens.[8]
MeO
OH
MeO
O
OH
O
O
O
O
O
OH
O
O
O
4'
1'
HO
O
O
10
(–)-spiroxin C (1)
11
stereospecific
photoredox
reaction
MeO OMe
MeO
OMe
MeO
O
Br OMe
14
OMe
OBn
+
H O
OH
4'
1'
O
OBn
1'
TBSO
HO
1'
13
12
MeO
OMe
TBSO
a
MeO
OMe
15
OMe
OBn
Br
Scheme 5. Retrosynthesis.
14
b
OHOMe
OBn
O
TBSO
Scheme 6 shows the preparation of chiral, non-racemic tetralone
15 via Noyori–Ikariya asymmetric
hydrogenation.[11]
21
Commercially available tetralone 16 was benzylated (BnBr,
K2CO3, DMF, RT, 2.5 h) to give ketone 17, which was subjected
to the hydrogenation in the presence of chiral Ru catalyst,
RuCl(p-cymene)[(R,R)-Ts-DPEN], (formic acid, triethylamine, RT,
42 h),[11] giving (R)-alcohol 18[12] in 89% yield with virtually
perfect enantioselectivity (>99% ee).[7,13] Acetylation of alcohol
(R)-18 followed by the benzylic oxidation[14] [(1) cerium(IV)
ammonium nitrate (CAN), CH3CN, H2O, 0 °C, 1.5 h; (2) TPAP,
TBSO
(R)-15
key NOE correlation
MeO
OMe
MeO
OMe
MeO
OMe
NOE
c
H
H OMe
OH
OMe
OBn
OMe
OH
4'
4'
1'
H
TBSO
TBSO
TBSO
NMO, MS4A, CH2Cl2, RT,
3
h], and
a
conventional
protection/deprotection sequence gave tetralone (R)-15 in 65%
yield over 5 steps from (R)-18.
22
13
22
Scheme 7. Synthesis of 22. a) sBuLi, THF, Et2O, 0 °C, 15 min, then (R)-15,
LaCl3·2LiCl, THF, Et2O, 0 °C, 15 min; b) SiO2, CH2Cl2, RT, 19 h 85% (2
steps); c) H2, 10% Pd/C, THF, MeOH, RT, 12 h, quant. (d.r. = 14:1).
OH
OBn
OBn
a
b
c
O
O
O
HO
(R)-18
Naphthalene 22 was oxidized with CAN, and the acidic reaction
medium led to cleavage of the TBS group, affording
naphthoquinone 12, ready for the key photoredox reaction
(Scheme 8). We were pleased to find that irradiation of
naphthoquinone 12 with a xenon lamp (>380 nm, 300 W,
CH3CN, RT, 1 h) nicely gave the corresponding photoredox
product.[17] At this stage, the crude material was purified by
medium-pressure liquid chromatography to give the desired
spiroether 11 in 65% yield over two steps and a small amount of
16
17
OBn
OBn
O
OBn
d, e
f, g
Ru Cl
TsN NH2
AcO
AcO
TBSO
Ph
Ph
Ru catalyst
(R)-19
(R)-20
(R)-15
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10.1002/anie.201705562
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COMMUNICATION
the C-4’ epimer 11’ (not shown) in 5% yield,[7] which arose from
the minor isomer of 22.[18] Thus, the photoredox reaction proved
applicable without problems to such a highly functionalized
naphthoquinone 12, bearing a free alkanol and a phenol. The
reactivity to undergo the Ito–Saegusa oxidation method,[24]
giving enone 29 in 63% yield, ready for the second epoxidation.
We were pleased to find that treatment of 29 with tBuOOH (TBD,
CH2Cl2, 0 °C, 10 min) gave bis-epoxide 30 as a single product,
relative stereochemistry of 11 was determined as in the following. whose stereochemistry was determined by single crystal X-ray
The oxidative spirocyclization of 11 was realized by using
PhI(OCOCF3)2, giving spiroacetal 23 in 86% yield. Among the
derivatizations for structural assignment, the TBS ether 24
derived from 23 (TBSCl, imidazole, DMF, RT, 2.5 h, 54%)[7] gave
diffraction analysis.[26] Thus, both of the two nucleophilic
epoxidations (25→28 and 29→30) proceeded with the desired
stereoselectivities, which could be rationalized by the convex–
concave analysis.
a
key evidence for the relative stereochemistry by NOE
correlation,[19] establishing that the key photoredox reaction on
MeO
O
MeO
O
MeO
O
a)
12→11 proceeded in a retentive manner.
Dess–Martin
periodinane
see text
MeO
OMe
MeO
O
OH
MeO
CH2Cl2
RT, 1.5 h
O
O
O
O
O
O
4'
quant.
O
HO
O
a
b
H
OMe
OH
H
O
OH
O
OH
23
25
10
4'
b)
MeO
O
TBSO
MeO
O
HO
HO
22
12
11
in acetone-d6
MeO
O
MeO
O
1 day
O
OH
O
O
4'
NOE
TMSO
TMSO
c
H
H
O
O
O
O
26
27
O
Si
HO
Scheme 9. Bis-enone formation from ketone 25.
23
24
MeO
O
MeO
O
Scheme 8. Photoredox reaction and oxidative cyclization. a) Ce(NH4)2(NO3)6,
H2O, CH3CN, 0 °C, 1.5 h; b) xenon lamp (300 W), CH3CN, RT, 1 h, 65% for 11,
5% for 11’ (2 steps); c) PhI(OCOCF3)2, EtOAc, 0 °C, 5 min, 86%.
Nu
O
MeO
O
O
O
a
O
O
O
O
O
O
With key spirocycle 23 in hand, the next task was the conversion
into bis-enone 10, the planned intermediate for a single step
installation of the two epoxides (Scheme 9a). Along these lines,
alcohol 23 was quantitatively converted to ketone 25 by Dess–
Martin oxidation.[20] However, attempts at the dehydrogenation of
25 into bis-enone 10 were all fruitless –either by IBX,[21]
Ph2Se2O3,[22] or the Mukaiyama oxidation.[23] The Ito–Saegusa
protocol[24] via the corresponding enol silyl ether gave only trace
amounts of bis-enone 10. The origin of the issue seemed the
high lability of the spiro acetal moiety, where facile elimination of
the C-4’ oxygen gave the corresponding naphthoquinone
derivatives. Such a tendency was already presaged by acid
lability of the foregoing spiro compounds 11 and 23, and the
chemical instability was particularly serious on 25 and its derived
enol silyl ether 26, which spontaneously aromatized to
naphthoquinone 27 even under neutral conditions (Scheme 9b).
Thus, we judged that bis-enone 10 is not a viable intermediate.
To circumvent this issue, we decided to transform the quinone
acetal 25 into epoxy ketone 28, in hope for improved chemical
stability (Scheme 10). Indeed, nucleophilic epoxidation of 25
(tBuOOH, TBD, CH2Cl2, RT, 3.5 h)[25] gave epoxy ketone 28 as a
single diastereomer, whose stereochemistry was assigned at a
later stage. Importantly, in contrast to ketone 25, epoxy ketone
28 showed an improved chemical stability, and furthermore good
O
Nu
25
28
MeO
O
O
Nu
O
O
O
O
b, c
d
MeO
O
O
O
O
Nu
29
MeO
9
O
OH O
O
O
e, f
O
O
O
O
O
O
O
O
(–)-spiroxin C (1)
30
X-ray structure of 30
Scheme 10. Endgame. a) tBuOOH, TBD, CH2Cl2, RT, 3.5 h, 96%; b) TMSOTf,
NEt3, CH2Cl2, RT, 30 min; c) Pd(OAc)2, CaCO3, CH3CN, 15 °C, 26 h, 63% (2
steps); d) tBuOOH, TBD, CH2Cl2, 0 °C, 10 min, 95%; e) BBr3, CH2Cl2, –78 °C,
20 min; f) K2CO3, MeOH, RT, 30 min, 55% (2 steps). TBD
triazabicyclo[4.4.0]dec-5-ene, TMSOTf
sulfonate.
=
1,5,7-
=
trimethylsilyl trifluoromethane-
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10.1002/anie.201705562
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COMMUNICATION
[9]
E. L. Eliel, S. H. Wilen, L. N. Mander, STEREOCHEMISTRY OF
ORGANIC COMPOUNDS; John Wiley & Sons, New York, 1994, pp
1119–1190.
For the final cleavage of the C-9 methyl ether, we had a prior
concern that the strong Lewis acidic conditions may deteriorate
the labile oxirane and acetal moieties. However, Heathcock’s
report nicely cleared this hurdle.[27,28] Brief exposure of
bisepoxide 30 to BBr3 (CH2Cl2, –78 °C, 20 min) effected
demethylation and also the oxirane-ring openings to form the
corresponding bromohydrins.[7] By treatment of the crude
products with K2CO3 in MeOH, the oxirane rings were
reconstructed, giving (–)-spiroxin C (1) in 55% yield over two
[10] For memory of chirality, see (a) T. Kawabata, K. Yahiro, K. Fuji, J. Am.
Chem. Soc. 1991, 113, 9694–9696. (b) K. Fuji, T. Kawabata, Chem.
Eur. J. 1998, 4, 373–376. (c) H. Zhao, D. C. Hsu, P. R. Carlier,
Synthesis 2005, 1–16. (d) V. Alezra, T. Kawabata, Synthesis 2016, 48,
2997–3016. For early examples in photochemistry, see (e) S. Sauer, A.
Schumacher, F. Barbosa, B. Giese, Tetrahedron Lett. 1998, 39, 3685–
3688. (f) B. Giese, P. Wettstein, C. Stähelin, F. Barbosa, M. Neuburger,
M. Zehnder, P. Wessig, Angew. Chem. Int. Ed. 1999, 38, 2586–2587;
Angew. Chem. 1999, 111, 2722–2724.
steps. The synthetic material
1 exhibited physical data
indistinguishable from the reported data in all respects (1H-, 13C
NMR, IR, UV, HRMS).[7]
[11] (a) A. Fujii, S. Hashiguchi, N. Uematsu, T. Ikariya, R. Noyori, J. Am.
Chem. Soc. 1996, 118, 2521–2522. (b) M. Watanabe, K. Murata, T.
Ikariya, J. Org. Chem. 2002, 67, 1712–1715.
Concerning the stereochemical integrity, assessment on the
samples of 30 and 1 by HPLC on chiral stationary phase proved
the enantiomeric purity (>99% ee).[29] The sign and magnitude of
the optical rotation of the synthetic material 1 matched those
[12] The absolute stereochemistry of (R)-18 was determined by modified
Mosher method: I. Ohtani, T. Kusumi, Y. Kashman, H. Kakisawa, J. Am.
Chem. Soc. 1991, 113, 4092–4096. For the detail, see: Supporting
Information.
22
reported for the natural product {synthetic [a]D –692 (c 0.650,
25
MeOH), lit. [a]D –706 (c 0.256, MeOH)}.[3a] The absolute
[13] The crude material of 17 could be used without problem for this
asymmetric reduction.
structures of the spiroxins relied on the exciton-coupled CD
study on a congener, (–)-spiroxin A,[3b] and the present study
has provided an independent validation.
[14] (a) K. Oyama, T. Kondo, J. Org. Chem. 2004, 69, 5240–5246. (b) M. N.
Kanvinde, S. A. Kulkarni, M. V. Paradkar, Synth. Commun. 1990, 20,
3259–3264.
In summary, the first enantioselective total synthesis of (–)-
spiroxin C (1) has been accomplished, featuring a stereospecific
photoredox reaction for construction of the key spiroether
structure. The synthetic route should be widely applicable to
other natural/unnatural congeners with potential biological
activities. Further work along these lines is in progress.
[15] A. Krasovskiy, F. Kopp, P. Knochel, Angew. Chem. Int. Ed. 2006, 45,
497–500; Angew. Chem. 2006, 118, 511–515.
[16] Silica gel 60N (spherical neutral, particle size 40–50 µm) from Kanto
Chemical was used.
[17] The preparative-scale reaction of naphthoquinone 12 was slow with
ambient light.
[18] Part of the C4’ epimer 11’ may also arise from the minor photoredox
reaction pathway of the major isomer 22 (invertive), which, however,
should be minimal, judging from the results of model study.
[19] Since the stereochemical assignment of 11 itself was difficult, the silyl
ether 24 was prepared for the NOE experiment.
Acknowledgments
[20] D. B. Dess, J. C. Martin, J. Org. Chem. 1983, 48, 4155–4156.
[21] (a) K. C. Nicolaou, T. Montagnon, P. S. Baran, Angew. Chem. Int. Ed.
2002, 41, 993–996; Angew. Chem. 2002, 114, 1035–1038. (b) E.
Quesada, M. Stockley, J. P. Ragot, M. E. Prime, A. C. Whitwood, R. J.
K. Taylor, Org. Biomol. Chem. 2004, 2, 2483–2495.
This research was supported by JSPS KAKENHI Grant
Numbers JP16H06351 and JP26810018. We are grateful to Prof.
Hidehiro Uekusa, Mr. Haruki Sugiyama, and Ms. Sachiyo Kubo
(Tokyo Institute of Technology) for X-ray diffraction analyses.
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Keywords: naphthoquinone • photoreaction • redox reaction •
spiroxin C •stereospecificity
[1]
[2]
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[4]
[5]
[28] Other reagents, such as MgI2·OEt2, CeCl3·7H2O and NaI, or AlCl3, were
also tested in a model study. Notably, the iodide-containing reagents
were ineffective, because the resulting a-iodoketone underwent further
reductive removal of the a-iodine, giving the corresponding “non-iodo”
b-hydroxy ketone, losing the opportunity to recover the desired epoxy
ketone structure.
[6]
[7]
[8]
The term cis/trans refers to the mutual relation of the oxy substituent
and the naphthoquinone moiety within the six-membered ring.
For the experimental procedures and the structure identification, see
Supporting Information.
[29] In our exploratory study, we prepared also the racemic samples of 30
and 1, which were used for these HPLC analyses. For HPLC analysis
on chiral stationary phase: DAICEL column (0.46 cm f 25 cm, flow rate
1.0 mL/min, l = 254 nm, 25 °C): 30; CHIRALPAK® IF, hexane/EtOAc =
The ratio of diastereomers was determined by HPLC analysis of the
crude materials, respectively. For detail, see Supporting Information.
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75/25, tR = 12.8 min for the synthetic material, 14.8 min for the
enantiomer. 1; CHIRALPAK® IB, hexane/EtOAc = 85/15, tR = 19.2 min
for the (+)-spiroxin C, 21.9 min for the (–)-spiroxin C.
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10.1002/anie.201705562
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Entry for the Table of Contents (Please choose one layout)
Layout 2:
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Y. Ando, A. Hanaki, R. Sasaki, K.
MeO
OH
MeO
O
OH
O
Ohmori, K. Suzuki*
O
oxidized
reduced
O
Page No. – Page No.
O
OH
H
O
OH
O
O
photoredox
reaction
Stereospecificity in Intramolecular
Photoredox Reactions of
HO
HO
O
retention
(–)-spiroxin C
Naphthoquinones: Total Synthesis of
(–)-Spiroxin C
The stereospecific conversion of naphthoquinone derivatives into the corresponding
spiroethers via intramolecular photoredox reaction has been developed. Based on
this method, the enantioselective total synthesis of (–)-spiroxin C, a highly
oxygenated dimeric naphthoquinone, has been achieved.
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