Grubbs carbene complex-catalyzed cleavage of allyl vic-diols to aldehydes with a co-oxidant: Application to the selective cleavage of huge marine molecules

Article abstract of DOI:10.1016/j.tet.2011.09.002

An oxidative cleavage of allyl vic-diols to aldehydes catalyzed by a Grubbs carbene complex using a co-oxidant has been established for the first time, with good yields. The utility of this selective cleavage reaction was demonstrated through the use of two huge marine molecules, symbiodinolide and N-p-BrBz palytoxin.

Full text of DOI:10.1016/j.tet.2011.09.002

Tetrahedron 67 (2011) 9622e9626
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Grubbs carbene complex-catalyzed cleavage of allyl vic-diols to aldehydes with
a co-oxidant: application to the selective cleavage of huge marine molecules
,
Chunguang Han a, Yoshi Yamano a, Fumitoshi Kakiuchi b, Kazuhiko Nakamura c, Daisuke Uemura c
*
a Department of Chemistry, Graduate School of Science, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8602, Japan
b Department of Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Yokohama 223-8522, Japan
c Department of Chemistry, Faculty of Science, Kanagawa University, Hiratsuka, Kanagawa 259-1293, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 21 July 2011
Received in revised form 1 September 2011
Accepted 2 September 2011
Available online 8 September 2011
An oxidative cleavage of allyl vic-diols to aldehydes catalyzed by a Grubbs carbene complex using a co-
oxidant has been established for the first time, with good yields. The utility of this selective cleavage
reaction was demonstrated through the use of two huge marine molecules, symbiodinolide and N-p-BrBz
palytoxin.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Grubbs carbene complex
Catalytic reaction
Marine huge molecule
Degradation reaction
1. Introduction
We report here the Grubbs II complex-catalyzed specific oxi-
dation of allyl vic-diols with a co-oxidant and the application of this
Transition metalecarbene complexes are well-recognized as
intermediates in homogeneous catalytic olefin metathesis.1 Among
these complexes, molybdenumealkylidene complexes (Schrock
catalyst)2 and rutheniumealkylidene complexes (Grubbs catalyst)3
have created new possibilities in organic synthesis for constructing
CeC double bonds.4 Several complexes are commercially available,
and, in particular, the second-generation Grubbs catalyst (Grubbs II
catalyst) has become an important tool for the synthesis of natural
products because of its high tolerance toward functional groups,
high stability, and high activity toward olefins.5 Grubbs II catalyst is
often used in ring-closing, ring-opening, and cross-metatheses of
olefins.5 Interestingly, however, Grubbs complexes are rarely used
as catalysts for other transformations of olefins.
Very recently, we reported the Grubbs II complex-mediated
specific oxidation of allyl vic-diols to the corresponding alde-
hydes.6 This oxidative vic-diol cleavage protocol is highly useful
because only vic-diols with an allylalcohol moiety are oxidized,
while dialkyl vic-diols are not consumed during the reaction. The
major drawback of this reaction is that a stoichiometric amount of
expensive Grubbs II complex must be used to achieve high
efficiency.
transformation to the degradation of huge marine molecules, such
as ‘super-carbon-chain compounds (SCC)’,7 symbiodinolide, and N-
p-BrBz-substituted palytoxin.
2. Results and discussion
We previously demonstrated that the Grubbs II complex 1
showed high activity for the stoichiometric oxidation of 1,6-
diphenyl-1,5-hexadiene-3,4-diol (2) to cinnamaldehyde (3) (94%
yield) (Eq. 1).6a The activities of other ruthenium complexes such as
RuCl3, RuO2, RuCl2(PPh3)3, and Grubbs I complexes in the reaction
of 2 were examined using a stoichiometric amount of the complex
(Eq. 1). In these cases, the yields decreased to 0e64%. Therefore,
Grubbs II complex was considered to be a suitable catalyst for this
reaction.
OH
ruthenium complex
Ph
H
Ph
(1 equivalent)
DCM, rt
Ph
(1)
O
OH
3
2
As a working hypothesis for oxidative cleavage of the CeC bond
at an allyl vic-moiety in a catalytic manner, we considered the re-
action pathway. The initial step involves ligand-exchange between
Grubbs II complex and the allyl vic-alcohol. In the second step, the
diol is oxidized to the corresponding aldehydes and the Ru complex
* Corresponding
author.
E-mail
address:
uemurad@kanagawa-u.ac.jp
(D. Uemura).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.09.002

C. Han et al. / Tetrahedron 67 (2011) 9622e9626
9623
is reduced to Ru(II) species. Oxidation of Ru(II) species with an
oxidant to regenerates Ru(IV) species.
The stereochemistries at C5, C6, and C7 of the C1ꢀC13 fragment
were assigned on the basis of the Universal NMR Database ap-
proach.10 The chemical shifts of H5 and H7 were observed at
We chose diallyl vic-diol 2 as a test substrate for the screening of
co-oxidants in the Grubbs II complex-catalyzed oxidation. The re-
action of 2 with a co-oxidant was carried out in the presence of
10 mol % Grubbs II catalyst in dichloromethane at room tempera-
ture. The results are shown in Table 1. The reaction in the absence of
a terminal oxidant afforded 3 in 6% yield (entry 1). A combination of
Grubbs II and Chloramine-T or NCS showed low catalytic activity
(entries 2 and 3). The use of O2, H2O2, or TBHP was not effective
(entries 4e6). Between two amine oxides screened (entries 7e8),
NMO functioned as a good co-oxidant and 3 was obtained in 73%
yield (entry 8). The oxidation using NaClO led to 3 in high yield
(90%) (entry 9).
d
3.97 ppm in D2O, which indicated the presence of a plane of
3
symmetry for fragment 7. Two contiguous JH,H constants
(3J5,6¼3J6,7¼4.5 Hz) are identical and fairly small (as a general trend,
3
a syn-diol gives a smaller JHH constant than the corresponding
anti-diol). These results are consistent with the universal NMR
database of 1,2,3-triol 1a (aaa), and therefore the relative stereo-
chemistries at C5, C6 and C7 could be proposed as 5R*, 6R*, and 7S*
(Scheme 1).
In addition, a (Z)-monoallyl anti-diol substructure in N-p-BrBz
palytoxin (9) was selectively cleaved in the presence of 50 mol %
Grubbs II catalyst and NaClO (6 equiv) in MeOH at room tempera-
ture (Fig. 1), and two degradation products, N-p-bromobenzoyl al-
Table 1
dehyde 1011 and
a,
b
-unsaturated aldehyde 11 (CfꢀC100 fragment),
Screening of oxidants for the catalytic cleavage of allyl vic-alcohol 2a
were obtained in Fig. 2. These results indicate that Grubbs II
complex-catalyzed selective cleavage using NaClO might be suit-
able for the conversion of both E- and Z-allyl vic-diols to aldehydes
in natural products, especially large polyol compounds for stereo-
structural analysis, since multiple vic-diol moieties could not be
cleaved during the reaction.
Another example of a diol cleavage reaction was also dem-
onstrated. Pseurotin A is a natural product of a fungal metabolite
with a diallyl diol moiety, and it possesses neuritogenic activity
in PC12 phaechromocytoma cells.12 Pseurotin A was subjected to
the catalytic diol cleavage conditions (Grubbs II catalyst
0.1 equivdNMO 20 equiv in MeOH/CH2Cl2; rt 4 h) and gave the
expected aldehyde 12 in >90% yield without any side products
(Scheme 2).
For the present catalytic cleavage of allyl vic-diols using NaClO,
we propose the reaction pathway shown in Scheme 3. Ru(II) species
C was oxidized by NaClO (or some other co-oxidant) to give the
oxoruthenium Ru(IV) species A. Ligand-exchange occurs between A
and allyl vic-diol B, and the diol is then oxidized to the corre-
sponding aldehydes and water. The Ru complex is reduced to Ru(II)
species C, thereby completing the catalytic cycle.
In summary, we have developed a new efficient method for the
Grubbs II complex-catalyzed oxidative cleavage of E- and Z-allyl vic-
diol using NaClO or some other co-oxidant under very mild reaction
conditions. We demonstrated the utility of this catalytic cleavage
for the first time using two huge marine molecules, symbiodinolide
and N-p-BrBz palytoxin. This reaction is highly useful for stereo-
structural analysis in natural products chemistry, especially in
polyene alcohol compounds, since this cleavage reaction gives only
simple products; i.e., while vic-diols with an allylalcohol moiety are
oxidized, dialkyl vic-diol (e.g., triol or tetraol) in the same molecule
is not.
Entry
Oxidant
Yield of 3b
1
2
3
4
5
6
7
8
9
None
Chloramine-T
NCS
O2
H2O2
TBHP
Pyridine-N-oxide
NMO
6%
10%
25%
29%
17%
4%
8%
73%
90%
NaClO
a
Reaction conditions: Grubbs II complex 1 (10 mol %), 2 (0.02 mmol), oxidant
(2 equiv), DCM (1 mL), rt.
b
Isolated yield based on 2.
Diallyl vic-diol substructures are not essential to achieve high
reactivity, since monoallyl vic-diol 4 was also oxidized under sim-
ilar reaction conditions except for the catalyst loading (20 mol %) to
give the corresponding aldehydes 3 and 5 in respective yields of
84% and 78% (Eq. 2). On the other hand, dialkyl vic-diol was com-
pletely inactive under these reaction conditions, although it had
been reported as a catalyzed oxidative cleavage to aldehydes with
O2 by Ru(PPh3)Cl2.8 These results indicate that at least one allyl vic-
diol substructure is essential for this Grubbs II complex-catalyzed
oxidative cleavage reaction. We envisioned that the present cata-
lytic cleavage of allyl vic-diols using NaClO as a co-oxidant could be
used for the selective degradation of natural products containing
multiple vic-diol moieties.
OH
Ph
H
20 mol % 1
Ph
3
+
(2)
Ph
3. Experimental
NaClO (2 equiv)
DCM, rt
5
O
84%
OH
4
78%
3.1. General information
Two huge marine molecules, symbiodinolide, and N-p-BrBz
palytoxin, contain allyl vic-diol and multiple vic-diol moieties and
were used as substrates to validate the practicability of the Grubbs
II complex-catalyzed oxidation of allyl vic-diols using NaClO. A seco
ester9 of symbiodinolide (6) was first obtained by methanolysis,
and the catalytic cleavage of 6 was then performed in the presence
of commercially available Grubbs II complex 1 (10 mol %) with
NaClO (7 equiv) in MeOH at room temperature for 4 h. The corre-
1H NMR spectra were recorded on a JEOL JNM-ECA800 spec-
trometer. Chemical shifts are expressed in parts per million relative
to residual chloroform (dH 7.26 for 1H), or CD3OD (dH 3.30 for 1H).
Coupling constants are reported in hertz (Hz) and the peak multi-
plicity is listed as follows: s, singlet; d, doublet; t, triplet; q, quartet;
m, multiplet. Peak assignments were made with the aid of the COSY
method. High-resolution mass spectra (HR-ESIMS) were obtained
on a PE Biosystems QSTAR mass spectrometer. Column chroma-
tography was performed with Wako Pure Chemical Silica-gel
(WakogelÒ C-300) and Nacalai Tesque Cosmosil 75C18-OPN. Merck
silica-gel 60 F254 plates were used for thin-layer chromatography
(TLC).
sponding ab
,
gd-unsaturated aldehyde 7 (C1ꢀC13 fragment) and
a
,b
-unsaturated aldehyde 8 (C14ꢀC250 fragment) were obtained in
respective yields of 86% and 76% due to the selective cleavage of (E)-
diallyl vic-diol (Scheme 1).

9624
selective cleavage
C. Han et al. / Tetrahedron 67 (2011) 9622e9626
OH
OH
OH
O
O
OH
HO
HO
OH
OH
OH
OH
O
OH OH OH
OH
O
OMe
OSO3Na
OH
1
HO
O
OH OH
H
OMe
MesN
Cl
NMes
Ph
HO
OH OH
OH OH
OH
Ru
Cl
10 mol %
7 (C1-C13)
PCy3
Grubbs II (1)
HO
HO
OH
OH
86% yield
OH
O
O
NaClO (7 equiv)
MeOH, RT, 4 h
O
OH OH OH
OH
OH
OH
HO
OH
OH
C115H199NNaO48
OH
H
O
H
HO
104
S
OH
O
O
NH OH
1'
OH
OH
O
25'
8 (C14-C25')
OH
HO
OH OH
76% yield
OH
OH
Seco Symbiodinolide (6)
Scheme 1. Selective cleavage of seco-symbiodinolide.
selective cleavage
OH
O
O
OH
OH
OH
O
O
HO
OH
OH
N
H
OH
O
OH
Br
OH
97
HO
HO
OH
OH
OH
OH
O
OH
OH
O
c
O
1
OH
5
OH
OH
OH
OH
OH
a
HO
N
H
N
H
O
H
OH
OH
HO
HO
OH
OH
OH
O
O
O
OH
HO
OH
H
O
50
OH
OH
HO
OH
OH
OH
OH
N-p-BrBz Palytoxin (9)
Fig. 1. Structure of N-p-BrBz palytoxin.
H
OH
NaClO
O
O
O
HO
C H
99 171
N O
H2O, aldehydes
2
41
Ru (II)
C
O
O
O
O
H
N
H
NaCl
OH
Br
OH
HO
OH
OH
10 (87%)
11
RuIV = O
A
MesN
HO
NMes
Fig. 2. Structure of degradation products of N-p-BrBz palytoxin.
Ru
O
Ph
R'
OH
OH
R'
R
O
H
R
B
Scheme 2. Selective cleavage of pseurotin A.
Scheme 3. Proposed reaction pathway for catalytic cleavage of allyl vic-diols using
NaClO.
3.2. Synthesis of 1,6-diphenyl-1,5-hexadiene-3,4-diol (2)
solution of cinnamaldehyde 3 (1.3 g, 9.8 mmol) at ꢀ78 ꢁC. After
being stirred at ꢀ78 ꢁC to ꢀ20 ꢁC, the reaction was quenched with
satd aqueous NaHCO3,10% aqueous NaHSO3, and triethylamine. The
whole mixture was filtered through a Celite pad and extracted with
Propionitrile (20 mmol) was added to TiI4 (11.1 g, 20 mmol) at
ambient temperature under an argon atmosphere. The solution was
stirred for 10 min, and to it was added a propionitrile (20 mL)

C. Han et al. / Tetrahedron 67 (2011) 9622e9626
9625
ethyl acetate (50 mLꢂ3). The combined organic extracts were dried
over anhydrous Na2SO4, and evaporated in vacuo. The residue was
subjected to column chromatography on silica-gel (CH2Cl2/
EtOAc¼2/1 as an eluent) to give 1,6-diphenyl-1,5-hexadiene-3,4-
0.004 mmol) and NaClO (16 mL, 0.04 mmol), and the mixture was
stirred for 4 h at room temperature in the dark. The reaction was
quenched with satd aqueous Na2SO3. The mixture was extracted
with CH2Cl2 (10 mLꢂ3). The combined organic extracts were dried
over anhydrous Na2SO4, and concentrated in vacuo. The residue
was subjected to column chromatography on silica-gel (eluent;
toluene) to give benzenepropenal 3 (2.2 mg, 84%) and benzene-
diol 2 (1.1 g, 83%) as a white solid. 1H NMR (CDCl3):
d 2.45 (br s,
2H), 4.26 (m, 2H), 6.25 (dd, J¼5.5, 15.8 Hz, 2H), 6.71 (d, J¼15.8 Hz),
7.23 (m, 2H), 7.29 (t, J¼7.6 Hz, 4H), 7.36 (J¼7.6 Hz, 4H). HRMS (ESI)
calcd for [MþNa]þ (C18H18O2Na) m/z 289.1204. Found 289.1210.
propanal 5 (2.1 mg, 78%); 1H NMR (CDCl3)
d 2.79 (m, 2H), 2.96 (m,
2H), 7.19 (m, 3H), 7.29 (m, 2H), 9.81 (br s, 1H). HR-ESIMS calcd for
3.3. Synthesis of 1,6-diphenyl-1-hexene-3, 4-diol (4)
[MþH]þ (C9H11O) m/z 135.081. Found 135.086.
1,6-Diphenyl-1,5-hexadiene-3,4-diol 2 (5.3 mg, 0.02 mmol) was
dissolved in MeOH (1.0 mL), and 0.4 mg of Rh/C (wt 5%) was added.
The solution was stirred under a hydrogen atmosphere (balloon) for
1 h at room temperature. The catalyst was removed through a filter
3.7. Methanolysis of symbiodinolide
To a stirred solution of symbiodinolide (4.4 mg, 1.5
mmol) in
MeOH (3.6 mL) was added Et3N (1.1 mL). After the reaction mixture
was stirred for 46 h at room temperature, it was concentrated under
reduced pressure to give the seco ester of symbiodinolide (4.5 mg,
100%) as a colorless solid that was sufficientlypure for the next stage.
HRMS (ESI) calcd for (Mþ2Na)2þ (C69H118N0.5Na1.5O29S0.5) m/z
1468.2481. Found 1468.2497.
(Minisart RC 4, 0.45 mm, Goettingen, Germany), and the filtrate was
evaporated and purified by HPLC [Develosil ODS-HG-5 (Ø
10ꢂ250 mm), 60% aqueous MeCN, flow rate 2 mL/min, RI detection]
to give monoallyl vic-diol 4 (3.2 mg, 60%, tR¼15.93e16.77 min) as
a white solid. 1H NMR (CDCl3):
d
1.71 (dddd, J¼5.2, 9.3, 9.8, 13.8 Hz,
1H), 1.86 (dddd, J¼3.4, 7.2, 10.3, 13.8 Hz, 1H), 2.66 (ddd, J¼7.2, 9.8,
13.6 Hz,1H), 2.84 (ddd, J¼5.2,10.3,13.6 Hz,1H), 3.53 (ddd, J¼3.4, 5.7,
9.3 Hz, 1H), 4.09 (dd, J¼5.7, 6.9 Hz, 1H), 6.26 (dd, J¼6.8, 15.8 Hz, 1H),
6.62 (d, J¼15.8 Hz, 1H), 7.12 (t, J¼7.3 Hz, 1H), 7.17e7.23 (m, 5H), 7.28
(t, J¼7.9 Hz, 2H), 7.38 (J¼7.9 Hz, 2H). HRMS (ESI) calcd for [MþNa]þ
(C18H20O2Na) m/z 291.1357. Found 291.1361.
3.8. Grubbs II complex-catalyzed cleavage of seco
symbiodinolide (6) using NaClO
A solution of seco symbiodinolide (6) (3.4 mg, 1.17
mmol) in
MeOH (0.3 mL) was degassed three times and then placed under an
argon atmosphere. To the above stirred solution was added the
second-generation Grubbs catalyst (29.4 mM in dichloromethane,
3.4. Stoichiometric oxidation of 1,6-diphenyl-1,5-hexadiene-
3,4-diol (2) to cinnamaldehyde (3)
4 mL, 0.12 mmol) and sodium hypochlorite solution (3 mL, 7.9 mmol),
and the mixture was stirred for 3 h at room temperature in the dark.
The reaction mixture was concentrated in vacuo, and the residue
was separated by RP-HPLC [Develosil ODS-HG-5, Ø 10ꢂ250 mm,
Nomura Chemical Co., Aichi, Japan, 20e50% aqueous MeCN, 60 min
A solution of 1,6-diphenyl-1,5-hexadiene-3,4-diol 2 (5.3 mg,
0.02 mmol) in anhydrous MeOH (0.8 mL) was degassed three times
and then placed under an argon atmosphere. To the above stirred
solution was added the ruthenium complex (0.02 mmol) in 0.2 mL
of DCM, and the mixture was stirred for 4 h at room temperature in
the dark. The reaction mixture was concentrated in vacuo, and the
residue was subjected to column chromatography on silica-gel
(eluent; toluene) to give trans-cinnamaldehyde 3: 3.4 mg (64%
yield by RuCl2(PPh3)3, 1.8 mg (34% yield by Grubbs I catalyst), trace
linear gradient, flow rate 2.0 mL/min, RI detection] to give ab
,
gd-
unsaturated aldehyde 7 (0.3 mg, 86%, tR¼9.13e10.07 min) and
a,b
-
unsaturated aldehyde 8 (2.3 mg, 76%, tR¼25.93e29.87 min).
3.8.1. ab,
gd-Unsaturated aldehyde 7 (C1eC13 fragment). 1H NMR
(CD3OD)
d
1.74 (m, 2H), 2.44 (dd, J¼8.7, 15.3 Hz, 1H), 2.47 and 2.52
(RuCl3), NR (RuO2). 1H NMR (CDCL3)
d
6.73 (dd, J¼7.6, 15.8 Hz, 1H),
(m, 2H), 2.56 (dd, J¼4.6,15.3 Hz,1H), 3.66 (m,1H), 3.67 (s, 3H, OMe),
3.81 (m, 1H), 3.89 (m, 1H), 4.23 (m, 1H), 6.09 (dd, J¼7.8, 15.2 Hz, 1H),
6.46 (m, 2H), 7.29 (dd, J¼10.1,15.2 Hz,1H), 9.49 (d, J¼7.8 Hz,1H); HR
ESI-TOF-MS m/z 325.1194 (MþNa)þ, calcd for C14H22O7Na:
325.1263.
7.44 (m, 3H), 7.49 (d, J¼15.8 Hz, 1H), 7.57 (m, 2H), 9.71 (d, J¼7.6 Hz,
1H). HR-ESIMS calcd for [MþH]þ (C9H9O) m/z 133.0656. Found
133.0653.
3.5. Typical procedure for screening of oxidants for the
catalytic cleavage of allyl vic-alcohol (2)
3.8.2.
a
,
b
-Unsaturated aldehyde 8 (C14ꢀC250 fragment). A colorless
solid; 1H NMR (CD3OD)
d
0.90 (t, J¼6.9 Hz, 3H, H250), 0.95 (d,
The solution of diallyl vic-diol
2
(5.3 mg, 0.02 mmol) in
J¼6.4 Hz, 3H, C70eMe), 1.01 (d, J¼6.5 Hz, 3H, C53eMe), 1.06 (d,
J¼6.9 Hz, 3H, C95eMe), 1.16 (m, 2H, H84a), 1.25 (m, 1H, H90a), 1.29
(m, 2H, H240), 1.30 (m, 2H, H230), 1.31 (m, 2H, H220), 1.33 (m, 2H,
H210), 1.42 (m, 2H, H190), 1.45 (m, 2H, H96), 1.45 (s, 3H, C30eMe),
1.37 and 1.45 (m, 2H, H52), 1.50 (m, 2H, H200), 1.51 (m, 2H, H80),
1.52 (m, 2H, H63), 1.53 (m, 2H, H78a, H92a), 1.38 and 1.58 (m, 4H,
H86, H88), 1.59 (m, 4H, H82, H84b, H90b), 1.30 and 1.60 (m, 2H,
H81), 1.62 (m, 1H, H74a), 1.66 (m, 2H, H45), 1.67 (m, 1H, H78b), 1.43
and 1.68 (m, 2H, H60), 1.70 (s, 6H, C38eMe, C90eMe), 1.70 (m, 2H,
H62a, H92b), 1.59 and 1.72 (m, 2H, H50), 1.64 and 1.72 (m, 2H, H70),
1.54 and 1.87 (m, 2H, H85), 1.49 and 1.89 (m, 2H, H31), 1.94 (m, 3H,
H62b, H89),1.49 and 1.95 (m, 2H, H100),1.49 and 1.97 (m, 2H, H160),
2.06 (m, 2H, H74b, H95), 2.17 and 2.21 (m, 2H, H39), 2.23 (m, 4H,
H43, H60), 2.17 and 2.26 (m, 2H, H35), 2.18 and 2.26 (m, 2H, H100),
2.28 and 2.37 (m, 2H, H25), 2.42 (m, 2H, H20), 2.43 (m, 1H, H53),
2.55 (m, 1H, H70), 2.33 and 2.63 (m, 2H, H68), 2.65 (d, J¼6.5 Hz, 1H,
H29), 2.93 (dd, J¼2.4, 6.2 Hz, 1H, H28), 2.98 (dd, J¼2.4, 4.5 Hz, 1H,
H27), 3.04 (t, J¼8.6 Hz, 1H, H72), 3.12 (dd, J¼1.7, 7.2 Hz, 1H, H94),
3.18 (m, 2H, H76, 98), 3.25 (m, 1H, H40), 3.37 (m, 1H, H180), 3.49 (m,
dichloromethane (0.9 mL) was degassed and then placed under an
argon atmosphere. To the above stirred solution was added the
second-generation catalyst (20 mM in dichloromethane, 0.1 mL,
0.002 mmol) and NaClO (16 mL, 0.04 mmol), and the mixture was
stirred for 4 h at room temperature in the dark. The reaction was
quenched with satd aqueous Na2SO3. The mixture was extracted
with CH2Cl2 (10 mLꢂ3). The combined organic extracts were dried
over anhydrous Na2SO4, concentrated in vacuo. The residue was
subjected to column chromatography on silica-gel (eluent; toluene)
to give trans-cinnamaldehyde 3 (4.8 mg, 90%) as a yellow liquid.
3.6. Catalytic cleavage of monoallyl vic-alcohol (4) to
benzenepropenal (3) and benzenepropanal (5)
The solution of monoallyl vic-diol 4 (5.4 mg, 0.02 mmol) in
dichloromethane (0.9 mL) was degassed and then placed under an
argon atmosphere. To the above stirred solution was added the
second-generation catalyst (40 mM in dichloromethane, 0.1 mL,

9626
C. Han et al. / Tetrahedron 67 (2011) 9622e9626
1H, H65), 3.51 (dd, J¼3.5, 10.1 Hz, 1H, H140), 3.56 (d, J¼3.0 Hz, 1H,
H120), 3.59 (d, J¼3.0 Hz, 1H, H102), 3.63 (m, 1H, H57), 3.64 (m, 1H,
H26), 3.68 (m, 1H, H50), 3.28 and 3.68 (m, 2H, H104), 3.69 (m, 2H,
H64, H73), 3.73 (m, 2H, H150, H170), 3.75 (m, 2H, H44, H83), 3.77 (m,
1H, H51), 3.80 (m, 1H, H71), 3.81 (m, 1H, H61), 3.82 (m, 2H, H58,
H110), 3.84 (m, 2H, H79, H97), 3.89 (m, 1H, H75), 3.90 (m, 1H, H130),
3.95 (m, 2H, H77, H91), 4.03 (m, 1H, H30), 4.05 (m, 1H, H93), 4.11 (d,
J¼7.6 Hz, 1H, H66), 4.12 (m, 1H, H101), 4.19 (m, 2H, H40, H99), 4.20
(m,1H, H32), 4.26 (m,1H, H49), 4.27 (m, 2H, H46, H69), 4.36 (m, 2H,
H36, H56), 4.87 (m, 1H, H59), 5.06 (d, J¼9.2 Hz, 1H, H80), 5.11 and
5.19 (br s, 2H, C67eCH2a,b), 5.07 and 5.14 (m, 2H, H24), 5.21 (d,
J¼8.7 Hz, 1H, H37), 5.52 (dd, J¼7.2, 13.6 Hz, 1H, H41), 5.55 (m, 2H,
H33, H54), 5.63 (m, 1H, H34), 5.67 (m, 1H, H48), 5.68 (m, 2H, H42,
H47), 5.74 (dd, J¼6.4, 15.2 Hz, 1H, H55), 6.27 (dd, J¼7.8, 15.6 Hz, 1H,
H15), 6.98 (dd, J¼4.6,15.6 Hz,1H, H16), 9.54 (d, J¼7.8 Hz,1H). HRMS
ca. 20 equiv) in MeOH (0.5 mL) was added a 0.01 M solution of
second-generation Grubbs catalyst (19 L, 0.1 equiv) in CH2Cl2. The
solution was allowed to stand for 4 h at room temperature. The
resultant mixture was directly subjected to preparative TLC (SiO2,
chloroform/methanol 9:1) to give the desired aldehyde 12 (0.6 mg)
as a colorless oil, in ca. 90% yield.
m
3.10.1.
a,b d 1.98 (3H, s),
-Unsaturated aldehyde. 1H NMR (CDCl3)
3.42 (3H, s), 4.00 (1H, br d, J¼14 Hz), 4.65 (1H, d, J¼14 Hz), 7.4e7.6,
8.2 (total 5H, arom.), 9.94 (1H, s); LCeMS 346.1 (MþH).
Acknowledgements
This work was supported in part by a Grant-in-Aid for Creative
Scientific Research (16GS0206) from JSPS, and by the G-COE pro-
gram in chemistry at Nagoya University from the Ministry of Edu-
cation, Science, Sports and Culture, Japan.
(ESI) calcd for (Mþ2Na)2þ (C62H106N0.5Na1.5O25.5S0.5
)
m/z
1316.1720. Found 1316.1758.
3.9. Grubbs II complex-catalyzed cleavage of N-p-BrBz
palytoxin (9) using NaClO
References and notes
1. Van Leeuwen, P. W. N. M. Homogeneous Catalysis; Kluwer Academic: Dordrecht,
2004, Chapter 16.
A solution of N-p-BzBr palytoxin (9) (4.8 mg,1.68 mmol) in MeOH
(0.4 mL) was degassed three times and then placed under an argon
atmosphere. To the above stirred solution was added the second-
2. (a) Schrock, R. R.; Murdzek, J. S.; Bazan, G. C.; Robbins, J.; DiMare, M.; O’Regan,
M. J. Am. Chem. Soc. 1990, 112, 3875; (b) Bazan, G. C.; Khosravi, E.; Schrock, R. R.;
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112, 8378; (c) Bazan, G. C.; Oskam, J. H.; Cho, H. N.; Park, L. Y.; Schrock, R. R. J.
Am. Chem. Soc. 1991, 113, 6899.
generation Grubbs catalyst (82.4 mM in dichloromethane, 10
mL,
0.82 mol) and sodium hypochlorite solution (4 L, 10.4 mol), and
m
m
m
the mixture was stirred for 5 h at room temperature in the dark. The
reaction mixture was concentrated in vacuo, and the residue was
separatedbyRP-HPLC [Develosil ODS-UG-5, Ø 10ꢂ250 mm, Nomura
Chemical Co., Aichi, Japan, 30e70% aqueous MeCN, 80 min linear
gradient, flow rate 2.0 mL/min, RI detection] to give two degradation
products: N-p-bromobenzoyl aldehyde 10 (0.7 mg, 87%,
3. (a) Nguyen, S. T.; Johson, L. K.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc. 1992,
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107, 2179; Angew. Chem., Int. Ed. Engl. 1995, 34, 2039; (d) Wu, Z.; Nguyen, S. T.;
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€
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a,b-unsaturated aldehyde 11.
A. Top. Catal. 1997, 4, 285; (c) Kirkland, T. A.; Grubbs, R. H. J. Org. Chem. 1997, 62,
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d
1.41 (m,
€
8141; (g) Furstner, A. Angew. Chem., Int. Ed. 2000, 39, 3012.
1H), 1.51 (m, 1H), 1.77 (m, 1H), 1.80 (m, 3H), 1.89 (m, 1H), 2.15 (dd,
J¼6.4, 13.5 Hz,), 2.51 (ddd, J¼1.4, 4.6, 16.3 Hz, 1H), 2.57 (ddd, J¼2.8,
8.2, 16.3 Hz, 1H), 3.35 (m, 1H), 3.77 (m, 1H), 3.87 (m, 1H), 4.17 (m,
1H), 4.34 (m, 2H), 4.41 (m, 1H), 4.49 (m, 1H), 4.57 (t, J¼5.9 Hz, 1H),
6.47 (br s, 1H, NH), 7.58 (d, J¼8.7 Hz, 2H, Ph), 7.65 (d, J¼8.7 Hz, 2H,
Ph), 9.76 (br s, 1H); HR ESI-TOF-MS m/z 504.1005 (MþNa)þ, calcd
for C22H28BrNO6Na: 504.0998.
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3.10. Grubbs II complex-catalyzed cleavage of pseurotin A
To a solution of pseurotin A (0.8 mg, 1.9 mmol, Enzo Life Sci-
ences, NY) and N-methylmorpholine N-oxide (50% in MeOH, 10 mL,