Chemo- and stereoselective six-membered oxonium ylide formation–[2,3]-sigmatropic rearrangement of 2-diazo-3-ketoesters with dirhodium(II) catalyst and its application to the synthesis of (+)-tanikolide

Article abstract of DOI:10.1016/j.tet.2019.03.012

Dirhodium(II)-catalyzed oxonium ylide formation–[2,3]-sigmatropic rearrangement of 6-allyloxy-2-diazo-3-ketoesters possessing a C-6 substituent is described. The reaction of 6-alkyl- or 6-aryl-substituted 6-allyloxy-2-diazo-3-ketoesters with a catalytic amount of Rh₂(S-PTTL)₄ proceeded in a chemoselective and stereoselective manner to provide 6-substituted 2-allyl-3-oxotetrahydropyran-2-carboxylates in good yields and with high diastereoselectivities. To demonstrate the utility of this sequential reaction, we conducted the total synthesis of (+)-tanikolide, in which the construction of the δ-lactone skeleton was achieved by employing a 2-iodobenzamide-catalyzed oxidative cleavage of tetrahydropyran-2-methanol.

Full text of DOI:10.1016/j.tet.2019.03.012

Tetrahedron xxx (xxxx) xxx
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Chemo- and stereoselective six-membered oxonium ylide
formatione[2,3]-sigmatropic rearrangement of 2-diazo-3-ketoesters
with dirhodium(II) catalyst and its application to the synthesis of
(
þ)-tanikolide
*
Hikari Jinnouchi, Hisanori Nambu, Kanae Takahashi, Tomoya Fujiwara, Takayuki Yakura
Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama 930-0194, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 13 February 2019
Received in revised form
Dirhodium(II)-catalyzed oxonium ylide formatione[2,3]-sigmatropic rearrangement of 6-allyloxy-2-
diazo-3-ketoesters possessing a C-6 substituent is described. The reaction of 6-alkyl- or 6-aryl-
substituted 6-allyloxy-2-diazo-3-ketoesters with a catalytic amount of Rh (S-PTTL) proceeded in a
2 4
7
March 2019
chemoselective and stereoselective manner to provide 6-substituted 2-allyl-3-oxotetrahydropyran-2-
carboxylates in good yields and with high diastereoselectivities. To demonstrate the utility of this
sequential reaction, we conducted the total synthesis of (þ)-tanikolide, in which the construction of the
Accepted 9 March 2019
Available online xxx
d
-lactone skeleton was achieved by employing a 2-iodobenzamide-catalyzed oxidative cleavage of tet-
Keywords:
rahydropyran-2-methanol.
Oxonium ylide
Rearrangement
Rhodium
©
2019 Elsevier Ltd. All rights reserved.
Chemoselectivity
Stereoselectivity
1
. Introduction
3-ketoesters, only a few examples of the sequential reaction
involving six-membered oxonium ylides have been described
[1a,7]. The Pirrung group disclosed that the reaction of 6-allyloxy-
2-diazo-3-ketoester 2a with dirhodium(II) tetraacetate in
The dirhodium(II)-catalyzed intramolecular oxonium ylide for-
mation from -diazocarbonyl compounds and subsequent [2,3]-
a
sigmatropic rearrangement represents one of the most direct and
powerful methods for the construction of substituted cyclic ethers
dichloromethane
provided
2-allyl-2-methoxycarbonyl-3-
oxotetrahydropyran (3a) by oxonium ylide formatione[2,3]-sig-
matropic rearrangement in 53% yield, with 2-cyclopentene-1-one 4
in 37% yield, which stems from methylene C-H insertion followed
by elimination of allyl alcohol (Scheme 2, A) [1a]. Meanwhile,
McKervey and co-workers reported an enantioselective version of
this sequential reaction [7], in which treatment of 2a with the chiral
[
1]. The effectiveness of this sequential reaction has been demon-
strated through the synthesis of a variety of natural products [2].
We have reported that a dirhodium(II)-catalyzed sequential reac-
tion proceeds with excellent stereoselectivity when applied to 5-
allyloxy-2-diazo-3-ketoesters possessing a C-5 substituent [3] and
is suitable for the synthesis of 2-epi-cinatrin C
1
dimethyl ester [4].
2 4
dirhodium(II) catalyst Rh (S-PTTL) [8] in hexane afforded 3a in
Furthermore, the divergent synthesis of (þ)-tanikolide (1), (4S)-
and (4R)-hydroxytanikolides, and nortanikolide has been recently
achieved by the stereoselective rearrangement of 5-allyloxy-2-
diazo-3-ketoesters, followed by ring expansion (Scheme 1) [5,6].
In contrast to the considerable number of examples reported for the
dirhodium(II)-catalyzed five-membered oxonium ylide formatione
54% yield with 33% ee. In these pioneering works, poor chemo-
selectivity and moderate product yield were observed, and there is
no information regarding the diastereoselectivity in similar re-
actions of 6-allyloxy-2-diazo-3-ketoesters possessing a C-6 sub-
stituent. As a part of our work on the development of oxonium ylide
formatione[2,3]-sigmatropic rearrangement and its application to
the synthesis of biologically active compounds, we report the
chemoselective and stereoselective six-membered oxonium ylide
formatione[2,3]-sigmatropic rearrangement of 6-alkyl- and 6-aryl-
substituted 6-allyloxy-2-diazo-3-ketoesters 2 catalyzed by dirho-
dium(II) catalyst and its application to the total synthesis of (þ)-1
[2,3]-sigmatropic rearrangement sequences of 5-allyloxy-2-diazo-
*
Corresponding author.
E-mail address: yakura@pha.u-toyama.ac.jp (T. Yakura).
https://doi.org/10.1016/j.tet.2019.03.012
040-4020/© 2019 Elsevier Ltd. All rights reserved.
0
Please cite this article as: H. Jinnouchi et al., Chemo- and stereoselective six-membered oxonium ylide formatione[2,3]-sigmatropic
rearrangement of 2-diazo-3-ketoesters with dirhodium(II) catalyst and its application to the synthesis of (þ)-tanikolide, Tetrahedron,
https://doi.org/10.1016/j.tet.2019.03.012

2
H. Jinnouchi et al. / Tetrahedron xxx (xxxx) xxx
Scheme 1. Synthesis of (þ)-tanikolide (1) and its analogues using five-membered
oxonium ylide formatione[2,3]-sigmatropic rearrangement.
Scheme 3. Preparation of 6-allyloxy-2-diazo-3-ketoesters 2.
conducted by treatment with allyl bromide or b-methallyl chloride
and sodium hydride in the presence of tetrabutylammonium iodide
in tetrahydrofuran (THF) to afford allyl ethers 7 in 48%e96% yields.
Upon removal of the tert-butyldimethylsilyl (TBS) protecting group
in 7 with tetrabutylammonium fluoride (TBAF), followed by Swern
oxidation, the resulting aldehydes were converted into
b-ketoesters
8
by treatment with methyl or tert-butyl diazoacetates and SnCl .
2
Finally, diazo transfer from p-acetamidobenzenesulfonyl azide (p-
ABSA) with trimethylamine furnished 6-substituted 2-diazo-3-
ketoesters 2 in 67%e98% yields.
2.2. Rh(II)-catalyzed oxonium ylide formatione[2,3]-sigmatropic
rearrangement
We next investigated the reaction of 6-butyl-substituted 6-
allyloxy-2-diazo-3-ketoester 2b in the presence of a dirhodium(II)
catalyst (Table 1). Treatment of 2b with 1 mol% of dirhodium(II)
tetraacetate in dichloromethane at room temperature for 2 h
afforded a diastereomeric mixture of oxonium ylide formatione
0
[
2,3]-sigmatropic rearrangement products 3b and 3b in 37% and 6%
yields, respectively, without any C-H insertion products (entry 1).
0
The diastereomeric ratio of 3b and 3b was determined to be 6.2:1
from the isolated yields of these isomers. The trans relationship
between the butyl substituent at C-6 and the migrated allyl group
Table 1
Rh(II)-catalyzed oxonium ylide formatione[2,3]-sigmatropic rearrangement of
methyl 6-allyloxy-2-diazo-3-oxodecanoate (2b).
Scheme 2. Rh(II)-catalyzed six-membered oxonium ylide formatione[2,3]-sigma-
tropic rearrangement of 6-allyloxy-2-diazo-3-ketoesters 2.
(Scheme 2, B).
2
. Results and discussion
yield (%)
dr
2.1. Preparation of 6-allyloxy-2-diazo-3-ketoesters 2
0
(3b:3b )a
0
entry
Rh(II) catalyst
solvent
3b
3b
1
2
3
4
5
6
7
Rh
Rh
Rh
Rh
2
2
2
2
(OCOCH
(OCOC
(OCOCPh
(OCOCF
3
)
4
CH
CH
CH
CH
CH Cl2
toluene
2
2
2
2
Cl
Cl
Cl
Cl
2
2
2
2
37
47
18
37
67
67
59
6
6
4
14
4
4
6.2:1
7.8:1
4.5:1
2.6:1
17:1
17:1
10:1
Initially, several 6-allyloxy-2-diazo-3-ketoesters 2 were pre-
7
H
15
)
4
pared from 4-(tert-butyldimethylsilyloxy)butanal (5) [9] as shown
in Scheme 3. The nucleophilic addition of various Grignard re-
agents, such as methyl, ethyl, isopropyl, butyl, allyl, phenyl, 4-
fluorophenyl, 4-methylphenyl, and 4-methoxyphenyl magnesium
halides, to aldehyde 5 provided the corresponding alcohols 6 in
good to high yields. Then, allyllation of the hydroxy group in 6 was
3
)
4
3
)
4
Rh (S-PTTL)4
Rh
Rh
2
2
2
(S-PTTL)
(S-PTTL)
4
2
4
hexane
6
a
Determined based on isolated yields of separable isomers 3b and 3b'.
Please cite this article as: H. Jinnouchi et al., Chemo- and stereoselective six-membered oxonium ylide formatione[2,3]-sigmatropic
rearrangement of 2-diazo-3-ketoesters with dirhodium(II) catalyst and its application to the synthesis of (þ)-tanikolide, Tetrahedron,
https://doi.org/10.1016/j.tet.2019.03.012

H. Jinnouchi et al. / Tetrahedron xxx (xxxx) xxx
3
at C-2 in the major isomer 3b was tentatively assigned due to the
similar stereoselectivity in the five-membered oxonium ylide for-
matione[2,3]-sigmatropic rearrangement of 5-substituted 5-
allyloxy-2-diazo-3-ketoesters [3e6,10]. As mentioned before, the
Rh(II)-catalyzed reaction of 2a gave C-6 methylene C-H insertion
product 4 in considerable yield (Scheme 2, A); no C-H insertion
product was observed in the reaction of 2b, despite having a more
reactive methyne C-H bond [11,12] at C-6. To further enhance the
product yield and diastereoselectivity, we evaluated the abilities of
other dirhodium(II) catalysts. The reaction of 2b with dirhodium(II)
tetraoctanoate improved both the product yield (3b: 47%, 3b': 6%)
and diastereoselectivity (3b:3b' ¼ 7.8:1, entry 2). In contrast, the
use of dirhodium(II) tetrakis(triphenylacetate) possessing a bulky
ligand decreased the yield (3b: 18%, 3b': 4%) and diaster-
eoselectivity (3b:3b' ¼ 4.5:1, entry 3). Conversely, the reaction with
decreased the product yield as well as diastereoselectivity (56%
0
combined yield of two diastereomers 3c and 3c , 3c:3c' ¼ 10:1).
Meanwhile, the reaction of diazoketoester 2d possessing a meth-
allyloxy group instead of an allyloxy group proceeded uneventfully
0
to give a 13:1 mixture of tetrahydropyranones 3d and 3d in 56%
combined yield. We then investigated the effect of the substituent
at C-6. The use of methyl group led to a decrease in diaster-
eoselectivity (3e:3e' ¼ 10:1). In contrast, the reaction of ethyl-
substituted diazoketoester 2f provided high diastereoselectivity
(3f:3f' ¼ 26:1). The presence of an isopropyl substituent at C-6
afforded excellent diastereoselectivity (3g:3g' ¼ 36:1). The reaction
of allyl-substituted diazoketoester 2h afforded a 14:1 mixture of
0
the corresponding tetrahydropyranones 3h and 3h in 61% com-
bined yield. We also found that use of an aromatic group as a C-6
substituent gave perfect diastereoselectivity; the reaction of aryl-
substituted diazoketoesters 2iel afforded the corresponding tet-
rahydropyranones 3iel as single diastereomer in 41%e85% yields.
These results clearly indicate that the diastereoselectivity improves
with the bulkiness of the C-6 substituent.
0
dirhodium(II) tetrakis(trifluoroacetate) provided 3b and 3b in
good yield (3b: 37%, 3b': 14%), albeit with low diastereoselectivity
(
3b:3b' ¼ 2.6:1, entry 4). We then examined the use of chiral
8
catalyst Rh
excellent stereoselectivity even in racemic reactions. Thus, the
treatment of 2b with 1 mol% of Rh (S-PTTL) afforded products in
higher yield (3b: 67%, 3b': 4%) with high diastereoselectivity
2 4
(S-PTTL) because it demonstrates high reactivity and
2
4
2.3. Synthesis of (þ)-tanikolide (1)
(
3b:3b' ¼ 17:1, entry 5) [13]. For the same catalyst, switching the
The successful outcome of the diastereoselective synthesis of
tetrahydropyranones using Rh (S-PTTL) -catalyzed oxonium ylide
2 4
solvent from dichloromethane to toluene gave the same product
yield and diastereoselectivity (entry 6), whereas the use of hexane
as a solvent provided lower product yield (3b: 59%, 3b': 6%) and
diastereoselectivity (3b:3b' ¼ 10:1, entry 7). From these results, it
formatione[2,3]-sigmatropic rearrangement sequence prompted
us to investigate the application of this reaction to the total syn-
thesis of natural product (þ)-tanikolide (1), isolated from the ma-
rine cyanobacterium Lyngbya majuscula from Tanikeli Island,
Madagascar (Scheme 4) [15]. In our previous synthesis of (þ)-1,
dirhodium(II)-catalyzed five-membered oxonium ylide formatione
2 4
can be concluded that Rh (S-PTTL) in dichloromethane consti-
tuted the optimal conditions for the reaction of 2a, affording perfect
chemoselectivity, good product yield, and high diastereoselectivity
in the six-membered oxonium ylide formatione[2,3]-sigmatropic
rearrangement sequence [14].
[
2,3]-sigmatropic rearrangement and subsequent N-heterocyclic
carbene-catalyzed ring expansion were used to construct the
d-
Having identified the effectiveness of the use of Rh
the catalyst, we examined the scope of the reaction with a variety of
-substituted 6-allyloxy-2-diazo-3-ketoesters 2cel in dichloro-
2 4
(S-PTTL) as
lactone skeleton [5,6]. On the other hand, the present method using
six-membered oxonium ylide formatione[2,3]-sigmatropic rear-
6
rangement is more easy and direct to construct the
d-lactone from
methane (Table 2). Switching from methyl ester to tert-butyl ester
the diazoketoester. And the relationship between the alkyl
Table 2
2 4
Rh (S-PTTL) -catalyzed oxonium ylide formatione[2,3]-sigmatropic rearrangement of various 6-allyloxy-2-diazo-3-ketoesters 2.
Please cite this article as: H. Jinnouchi et al., Chemo- and stereoselective six-membered oxonium ylide formatione[2,3]-sigmatropic
rearrangement of 2-diazo-3-ketoesters with dirhodium(II) catalyst and its application to the synthesis of (þ)-tanikolide, Tetrahedron,
https://doi.org/10.1016/j.tet.2019.03.012

4
H. Jinnouchi et al. / Tetrahedron xxx (xxxx) xxx
Scheme 5. Total synthesis of (þ)-tanikolide (1).
Scheme 4. Stereoselective synthesis of tetrahydropyran 3m employing Rh(II)-
catalyzed oxonium ylide formatione[2,3]-sigmatropic rearrangement.
(DMF) afforded dihydropyran 13 in 51% yield. Catalytic hydroge-
substituent at C-6 and the migrated allyl group at C-2 in the major
product 3, which is now temporally assigned to be trans, can be
determined by the achievement of the synthesis. We initially
investigated the stereoselective synthesis of tetrahydropyranone
nation of both cyclic and side alkenes in 13, followed by hydride
reduction of the methyl ester moiety with diisobutylaluminum
hydride (DIBAL-H), furnished primary alcohol 14 in 87% yield. After
protection of the hydroxy group as its benzyl (Bn) ether with benzyl
bromide, deprotection of the TBS ether with TBAF provided alcohol
15 in 87% yield. Then, the oxidative cleavage of tetrahydropyran-6-
3
m from L-glutamic acid. To this end, conversion of L-glutamic acid
into secondary alcohol 9 was conducted according to the literature
procedure [16]. The allyllation of the hydroxy group in 9 was
accomplished by treatment with allyl bromide, silver(I) oxide,
calcium sulfate, and a molecular sieve (MS) 4 Å in the dark,
affording allyl ether 10 in 92% yield based on recovered starting
material (brsm). After removing the acetyl group with potassium
carbonate in methanol, Swern oxidation of the resulting hydroxy
group provided the corresponding aldehyde, which was subse-
methanol 15 to
oped an environmentally benign method for the oxidative cleavage
of tetrahydrofuran-2-methanols to -lactones using 2-
d-lactone 17 was investigated. We recently devel-
g
a
iodobenzamide catalyst [18,19]. Therefore, we selected the 2-
iodobenzamide-catalyzed oxidative cleavage for the conversion
into d-lactone. The reaction of 15 with 5 mol% of [4-iodo-3-(iso-
propylcarbamoyl)phenoxy]acetic acid (16) [19], 4 equivalents of
Oxone, and 1 equivalent of 2,6-di-tert-butyl-4-hydroxytoluene
2
quently treated with methyl diazoacetate and SnCl to afford b-
ketoester 11. Diazo transfer from p-acetamidobenzenesulfonyl
azide (p-ABSA) to 11 provided (6S)-6-allyloxydiazoketoester 2m in
(BHT), which suppressed undesired benzylic oxidation [19], in
ꢁ
CH
3
NO
2
/DMF (10:1) at 50 C provided the corresponding
d-lactone
9
8% yield. Finally, the dirhodium(II)-catalyzed oxonium ylide for-
17 in 66% yield after 22 h. Finally, hydrogenolysis of the benzyl
ether in the presence of Pearlman's catalyst (Pd(OH) /C) in meth-
matione[2,3]-sigmatropic rearrangement of 2m gave 3m with
perfect diastereoselectivity; the reaction of diazoketoester 2m with
2
2
4
25
anol furnished (þ)-1, [
0.65, CHCl )}, in quantitative yield. The spectroscopic data ( H and
C NMR) of the synthetic product were consistent with those re-
a
]
D
3
þ2.9 (c 0.51, CHCl ) {lit. [15] [
a]
D
þ2.3 (c
1
1
mol% of Rh
for 3 h produced the corresponding 3m virtually as a sole diaste-
reomer (dr ¼ >48:1) in 71% yield. Interestingly, the use of Rh (R-
PTTL) as a catalyst slightly prolonged the reaction time (3.5 h) and
2
(S-PTTL)
4
in dichloromethane at room temperature
3
13
ported for natural (þ)-1 [15]. Because the major isomer 3m of the
dirhodium(II)-catalyzed oxonium ylide formatione[2,3]-sigma-
tropic rearrangement of 2m was converted into (þ)-tanikolide (1),
the diastereoselectivity in the present rearrangement of 2 was
confirmed to be as expected.
2
4
improved the product yield (90%). These results suggest that a small
matched/mismatched effect between optically active starting ma-
terial and chiral catalyst might be occurring.
With 3m in hand, we then examined the total synthesis of
tanikolide (1) involving an oxidative cleavage to
d-lactone (Scheme
3. Conclusion
5
). To introduce a long alkyl side chain, cross metathesis between
alkene 3m and 1-decene was carried out. The reaction of 3m with
an excess amount of 1-decene in the presence of Grubbs 2nd
catalyst provided a 9:1 mixture of (E)- and (Z)-alkenes 12 in 86%
yield. Next, deoxygenation of the ketone is mandatory before per-
A chemoseletive and stereoselective six-membered oxonium
ylide formatione[2,3]-sigmatropic rearrangement of 2-diazo-3-
ketoesters using dirhodium(II) catalyst has been developed. The
reaction of 6-alkyl- or 6-aryl-substituted 6-allyloxy-2-diazo-3-
oxocarboxylates with a catalytic amount of Rh (S-PTTL) pro-
forming the oxidative cleavage to the
d-lactone. Following our
2
4
previous procedure for the synthesis of tanikolide from a dihy-
drofuranone intermediate [5,6], we carried out deoxygenation of
the ketone in 12 using WolffꢀKishner-type reduction [17]; after
conversion of ketone 12 into tosylhydrazone with tosylhydrazine in
ceeded in a chemoseletive and stereoselective manner to afford 6-
substituted 2-allyl-3-oxotetrahydropyran-2-carboxylates in good
yields with high diastereoselectivity. In addition, the total synthesis
of (þ)-tanikolide has been achieved by employing the present
Rh(II)-catalyzed oxonium ylide formatione[2,3]-sigmatropic
3
THF, the reduction with NaBH CN in N,N-dimethylformamide
Please cite this article as: H. Jinnouchi et al., Chemo- and stereoselective six-membered oxonium ylide formatione[2,3]-sigmatropic
rearrangement of 2-diazo-3-ketoesters with dirhodium(II) catalyst and its application to the synthesis of (þ)-tanikolide, Tetrahedron,
https://doi.org/10.1016/j.tet.2019.03.012

H. Jinnouchi et al. / Tetrahedron xxx (xxxx) xxx
5
rearrangement and the 2-iodobenzamide-catalyzed oxidative
cleavage of tetrahydropyran-2-methanol to -lactone. Further
4.2.2. tert-Butyl 2-allyl-6-butyl-3-oxotetrahedropyran-2-
carboxylates (3c and 3c )
0
d
application of the present method to the synthesis of a variety of
natural products containing tetrahydropyran is currently in
progress.
Rh(II)-catalyzed oxonium ylide formatione[2,3]-sigmatropic
rearrangement of 2c (65 mg, 0.20 mmol) according to the typical
procedure provided 3c (30 mg, 52%) and 3c' (3 mg, 5%) as colorless
ꢀ1
oils. 3c: IR (neat, cm
1641, 1436, 1227, 1144, 1083, 917, 734; H NMR (500 MHz, CDCl
5.80 (ddt, J ¼ 17.2, 10.3, 7.4 Hz, 1H), 5.14 (d, J ¼ 17.2 Hz, 1H), 5.11 (d,
J ¼ 10.3 Hz, 1H), 3.81e3.75 (m, 1H), 2.73 (dd, J ¼ 14.6, 6.9 Hz, 1H),
.66 (dd, J ¼ 14.6, 6.9 Hz, 1H), 2.68e2.61 (m, 1H), 2.38 (quint,
J ¼ 8.6 Hz, 1H), 2.02e1.96 (m, 2H), 1.77e1.69 (m, 1H), 1.58e1.43 (m,
) n 3080, 2955, 2933, 2872, 2863, 1753, 1728,
1
4
. Experimental section
3
)
d
4.1. General
2
Melting points were determined using a Yanaco micro melting
13
point apparatus and are uncorrected. Optical rotations were
determined using a JASCO P-2100 polarimeter. Infrared (IR) spectra
were recorded on a JASCO FT/IR-460 Plus spectrophotometer and
2H), 1.45 (s, 9 H), 1.38e1.29 (m, 3H), 0.91 (t, J ¼ 7.4 Hz, 3H); C NMR
(125 MHz, CDCl 206.6, 167.8, 131.9, 118.9, 86.7, 82.5, 72.9, 37.8,
3
) d
35.63, 35.60, 28.9, 27.8, 22.6, 14.0; HRMS (FAB) m/z calcd for
ꢀ
1
1
(M þ H)þ 297.2066, found 297.2071.
absorbance bands are reported in wavenumber (cm ). H NMR
spectra were recorded on JEOL JNM-ECX400P (400 MHz) spec-
trometer. Chemical shifts are reported relative to internal standard
17 29 4
C H O
4
.2.3. Methyl 6-butyl-2-methallyl-3-oxotetrahedropyran-2-
(
tetramethylsilane at
d
H
0.00 or CDCl
3
at
d
H
7.26). Data are pre-
0
carboxylates (3d and 3d )
sented as follows: chemical shift (
d
, ppm), multiplicity (s ¼ singlet,
Rh(II)-catalyzed oxonium ylide formatione[2,3]-sigmatropic
rearrangement of 2d (59 mg, 0.20 mmol) according to the typical
procedure provided 3d (28 mg, 51%) and 3d' (2 mg, 5%) as colorless
d ¼ doublet, t ¼ triplet, quint ¼ quintet, m ¼ multiplet, br ¼ broad),
1
3
coupling constant and integration. C NMR spectra were recorded
on JEOL JNM-ECX400P (100 MHz) spectrometer. The following in-
ꢀ1
oils. 3d: IR (neat, cm
1
) n 3077, 2954, 2933, 2862, 1752, 1732, 1647,
13
ternal reference was used (CDCl
3
at
d
77.0). All C NMR spectra
1
376, 1215, 1091, 981, 898, 733; H NMR (500 MHz, CDCl
J ¼ 1.7 Hz, 1H), 4.81 (dd, J ¼ 2.3, 1.1 Hz, 1H), 3.87e3.81 (m, 1H), 3.75
s, 3H), 2.86 (d, J ¼ 14.3 Hz, 1H), 2.68 (d, J ¼ 14.3 Hz, 1H), 2.66 (ddd,
J ¼ 16.9, 6.3, 4.0 Hz, 1H), 2.47 (ddd, J ¼ 16.9, 10.0, 7.4 Hz, 1H),
.06e1.95 (m, 2H),1.77e1.71 (m,1H), 1.76 (s, 3H),1.57e1.50 (m, 1H),
3
) d 4.86 (t,
were determined with complete proton decoupling. High-
resolution mass spectra (HRMS) were determined with JEOL JMS-
GCmate II and JEOL JMS-AX505HAD instruments. Column chro-
matography was performed on Silica Gel 60 PF254 (Nacalai Tesque)
and Kanto silica gel 60 N (63e210 mesh) under pressure. Analytical
thin layer chromatography (TLC) was carried out on Merck Kie-
selgel 60 F254 plates. Visualization was accomplished with UV light
and phosphomolybdic acid stain solution followed by heating.
(
2
1
13
.46e1.39 (m, 1H), 1.37e1.25 (m, 3H), 0.90 (t, J ¼ 6.9 Hz, 3H);
C
NMR (125 MHz, CDCl
3
)
d
206.0, 169.2, 140.3, 115.1, 87.6, 72.3, 52.8,
3
5.5, 29.2, 27.8, 23.68, 23.66, 22.6, 14.1, 13.9; HRMS (FAB) m/z calcd
(M þ H)þ 269.1753, found 269.1754.
25 4
for C15H O
4
.2. Rh(II)-catalyzed oxonium ylide formatione[2,3]-sigmatropic
4
.2.4. Methyl 2-allyl-6-methyl-3-oxotetrahedropyran-2-
rearrangement of 6-allyloxy-2-diazo-3-ketoesters 2
0
carboxylates (3e and 3e )
Rh(II)-catalyzed oxonium ylide formatione[2,3]-sigmatropic
rearrangement of 2e (48 mg, 0.20 mmol) according to the typical
procedure provided 3e (20 mg, 47%) and 3e' (2 mg, 5%) as colorless
4
.2.1. Methyl 2-allyl-6-butyl-3-oxotetrahedropyran-2-carboxylates
0
(3b and 3b ); typical procedure (Table 1, entry 5)
2 2
A solution of diazoketoester 2b (57 mg, 0.20 mmol) in CH Cl
ꢀ
1
oils. 3e: IR (neat, cm
) n 3080, 2979, 2953, 2933, 1752, 1728, 1641,
(
0
N
1 mL) was added dropwise to a solution of Rh
.002 mmol, 1 mol%) in CH Cl (1 mL) at room temperature under
. After stirring at room temperature for 2 h, the reaction mixture
2 4
(S-PTTL) (2.8 mg,
1
1437, 1227, 1147, 1076, 994, 916, 734; H NMR (400 MHz, CDCl )
3
2
2
d
5.78 (ddt, J ¼ 17.6, 10.0, 7.2 Hz, 1H), 5.16 (ddd, J ¼ 17.0, 3.2, 2.0 Hz,
2
1
3
H), 5.13 (ddd, J ¼ 10.0, 2.0, 1.2 Hz, 1H), 4.11e4.03 (m, 1H), 3.76 (s,
H), 2.80 (ddt, J ¼ 14.4, 6.8, 1.2 Hz, 1H), 2.74 (ddt, J ¼ 14.4, 6.8, 1.2 Hz,
was evaporated and the residue was purified by column chroma-
tography (silica gel, 7% EtOAc in hexane) to provide 3b (34 mg, 67%)
and 3b' (2 mg, 4%) as colorless oils. 3b: IR (neat, cm
ꢀ1
1H), 2.65 (ddd, J ¼ 16.9, 5.6, 4.4 Hz, 1H), 2.48 (ddd, J ¼ 16.9, 10.4,
) n 3080, 2955,
13
7
.6 Hz, 1H), 2.07e1.95 (m, 2H), 1.34 (d, J ¼ 6.4 Hz, 3H); C NMR
2
933, 2872, 2863, 1753, 1728, 1641, 1436, 1227, 1144, 1083, 917, 734;
1
(100 MHz, CDCl
3
3
)
d
205.6, 169.1, 131.5, 119.3, 87.0, 68.8, 52.8, 37.5,
H NMR (500 MHz, CDCl
3
)
d
5.78 (ddt, J ¼ 17.2, 10.3, 7.4 Hz, 1H), 5.15
þ
5.6, 30.9, 21.4; HRMS (EI) m/z calcd for C11
16
H O
4
(M) 212.1049,
(
(
2
d, J ¼ 17.2 Hz, 1H), 5.13 (d, J ¼ 10.3 Hz, 1H), 3.86e3.80 (m, 1H), 3.75
found 212.1052.
s, 3H), 2.81 (dd, J ¼ 14.3, 6.9 Hz, 1H), 2.73 (dd, J ¼ 14.3, 6.9 Hz, 1H),
.66 (ddd, J ¼ 17.0, 6.0, 4.6 Hz, 1H), 2.46 (ddd, J ¼ 17.0, 9.7, 7.4 Hz,
H), 2.06e1.96 (m, 2H), 1.75e1.67 (m, 1H), 1.56e1.41 (m, 2H),
1
4.2.5. Methyl 2-allyl-6-ethyl-3-oxotetrahedropyran-2-carboxylates
13
0
1
CDCl
.38e1.26 (m, 3H), 0.91 (t, J ¼ 6.9 Hz, 3H); C NMR (125 MHz,
(3f and 3f )
3
)
d
206.1, 169.0, 131.5, 119.3, 87.1, 72.3, 52.8, 37.3, 35.7, 35.4,
Rh(II)-catalyzed oxonium ylide formatione[2,3]-sigmatropic
rearrangement of 2f (51 mg, 0.20 mmol) according to the typical
procedure provided 3f (26 mg, 57%) and 3f' (2 mg, 2%) as colorless
þ
2
2
2
9.3, 27.8, 22.6, 14.0; HRMS (FAB) m/z calcd for C14
H
23
O
4
(M þ H)
ꢀ
1
55.1596, found 255.1596. 3b': IR (neat, cm
) n 3076, 2950, 2925,
ꢀ
1
853, 1703, 1636, 1614, 1516, 1458, 1436, 1308, 1250, 1178, 1068,
oils. 3f: IR (neat, cm
) n 3080, 2957, 2934, 2879, 1752, 1727, 1642,
1
1
1046, 945, 829, 775; H NMR (500 MHz, CDCl
3
)
d
5.81 (ddt, J ¼ 17.2,
1436, 1227, 1146, 1076, 995, 972, 921; H NMR (500 MHz, CDCl )
3
1
0.3, 6.9 Hz, 1H), 5.09 (ddd, J ¼ 17.2, 3.4, 1.7 Hz, 1H), 5.07 (ddd,
d
5.78 (ddt, J ¼ 17.2, 9.7, 6.9 Hz, 1H), 5.16 (ddd, J ¼ 17.2, 2.9, 1.7 Hz,
J ¼ 10.3, 3.4, 1.1 Hz, 1H), 4.00e3.95 (m, 1H), 3.74 (s, 3H), 2.70 (ddt,
J ¼ 14.0, 7.4, 1.1 Hz, 1H), 2.58 (ddt, J ¼ 14.0, 6.9, 1.1 Hz, 1H), 2.54 (ddd,
J ¼ 15.8, 5.4, 3.4 Hz, 1H), 2.48 (ddd, J ¼ 15.8, 12.0, 5.7 Hz, 1H),
1H), 5.13 (d, J ¼ 9.7 Hz,1H), 3.80e3.78 (m, 1H), 3.76 (s, 3H), 2.81 (dd,
J ¼ 14.3, 6.9 Hz, 1H), 2.73 (dd, J ¼ 14.3, 6.9 Hz, 1H), 2.67 (ddd,
J ¼ 16.6, 6.3, 4.0 Hz, 1H), 2.46 (ddd, J ¼ 16.6, 10.6, 7.4 Hz, 1H),
2.07e1.95 (m, 2H), 1.73 (ddd, J ¼ 20.9, 14.9, 7.4 Hz, 1H), 1.58 (ddd,
2
.04e1.99 (m, 1H), 1.87e1.78 (m, 1H), 1.68e1.58 (m, 2H), 1.52e1.30
13
13
(
1
m, 4H), 0.92 (t, J ¼ 7.4 Hz, 3H); C NMR (125 MHz, CDCl
3
)
d
203.8,
J ¼ 20.9, 7.4, 5.1 Hz, 1H), 0.98 (t, J ¼ 7.4 Hz, 3H); C NMR (125 MHz,
69.6, 131.9, 118.7, 86.7, 73.5, 52.4, 39.5, 37.5, 35.0, 32.1, 27.6, 22.6,
3
CDCl ) d 206.1, 169.0, 131.5, 119.3, 87.1, 73.6, 52.8, 37.3, 35.6, 28.9,
14.0; HRMS (FAB) m/z calcd for C14
23
H O
4
(M þ H)þ 255.1596, found
28.6, 10.2; HRMS (FAB) m/z calcd for C12
found 227.1298.
H
19
O
4
(M þ H)þ 227.1283,
2
55.1603.
Please cite this article as: H. Jinnouchi et al., Chemo- and stereoselective six-membered oxonium ylide formatione[2,3]-sigmatropic
rearrangement of 2-diazo-3-ketoesters with dirhodium(II) catalyst and its application to the synthesis of (þ)-tanikolide, Tetrahedron,
https://doi.org/10.1016/j.tet.2019.03.012

6
H. Jinnouchi et al. / Tetrahedron xxx (xxxx) xxx
4
.2.6. Methyl 2-allyl-6-isopropyl-3-oxotetrahedropyran-2-
4.2.10. rel-(2R,6S)-Methyl 2-allyl-6-(4-tolyl)-3-
oxotetrahedropyran-2-carboxylate (3k)
0
carboxylates (3g and 3g )
Rh(II)-catalyzed oxonium ylide formatione[2,3]-sigmatropic
rearrangement of 2g (54 mg, 0.20 mmol) according to the typical
procedure provided 3g (36 mg, 75%) and 3g' (1 mg, 2%) as colorless
Rh(II)-catalyzed oxonium ylide formatione[2,3]-sigmatropic
rearrangement of 2k (48 mg, 0.15 mmol) according to the typical
procedure provided 3k (30 mg, 69%) as a colorless oil: IR (neat,
ꢀ
1
ꢀ1
oils. 3g: IR (neat, cm
436, 1388, 1368, 1279, 1227, 1142, 1069, 982, 922; H NMR
500 MHz, CDCl
5.78 (ddt, J ¼ 17.2, 10.3, 6.9 Hz, 1H), 5.15 (ddd,
)
n
3080, 2959, 2931, 2875, 1753, 1730, 1642,
cm
) n 3079, 3013, 2953, 2925, 2865, 1752, 1725, 1641, 1517, 1437,
1
1
1
1279, 1227, 1142, 1106, 1071, 995, 979, 914, 816; H NMR (400 MHz,
CDCl
(
3
)
d
3
)
d
7.34 (d, J ¼ 7.6 Hz, 2H), 7.18 (d, J ¼ 7.6 Hz, 2H), 5.88e5.77
J ¼ 17.2, 3.4, 1.7 Hz, 1H), 5.12 (ddd, J ¼ 10.3, 3.4, 1.1 Hz, 1H), 3.75 (s,
(m, 1H), 5.19 (ddd, J ¼ 17.2, 3.2, 1.6 Hz, 1H), 5.15e5.12 (m, 1H), 4.21
(dd, J ¼ 11.6, 2.8 Hz, 1H), 3.79 (s, 0.6H, minor), 3.76 (s, 2.4H, major),
3
1
4
H), 3.52 (ddd, J ¼ 9.2, 6.9, 5.4 Hz, 1H), 2.81 (ddt, J ¼ 14.3, 6.9, 1.1 Hz,
H), 2.72 (ddt, J ¼ 14.3, 6.9, 1.1 Hz, 1H), 2.67 (ddd, J ¼ 16.9, 6.0,
.6 Hz, 1H), 2.44 (ddd, J ¼ 16.9, 9.2, 7.2 Hz, 1H), 2.05e2.00 (m, 2H),
13
2.86 (d, J ¼ 7.6 Hz, 2H); C NMR (100 MHz, CDCl
3
) d 205.3, 186.3,
169.0, 137.8, 131.5, 129.2, 126.0,119.6, 87.4, 74.4, 52.9, 37.9, 36.4, 31.1,
þ
1
3
7
C
.85 (quint, J ¼ 6.9 Hz, 1H), 1.01 (d, J ¼ 6.9 Hz, 3H), 0.93 (d, J ¼ 6.9 Hz,
21.1; HRMS (EI) m/z calcd for C17
20
H O
4
(M) 288.1362, found
13
H); C NMR (125 MHz, CDCl
3
)
d
206.4, 169.0, 131.5, 119.2, 87.2,
288.1394.
7.1, 52.7, 37.3, 35.9, 33.0, 26.5, 18.8, 18.4; HRMS (FAB) m/z calcd for
þ
13 21
H O
4
(M þ H) 241.1440, found 241.1480.
4.2.11. rel-(2R,6S)-Methyl 2-allyl-6-(4-methoxyphenyl)-3-
oxotetrahedropyran-2-carboxylate (3l)
4
.2.7. Methyl 2,6-diallyl-3-oxotetrahedropyran-2-carboxylates (3h
Rh(II)-catalyzed oxonium ylide formatione[2,3]-sigmatropic
rearrangement of 2l (66 mg, 0.20 mmol) according to the typical
procedure provided 3l (25 mg, 41%) as a colorless oil: IR (neat,
0
and 3h )
Rh(II)-catalyzed oxonium ylide formatione[2,3]-sigmatropic
ꢀ1
rearrangement of 2h (53 mg, 0.20 mmol) according to the typical
procedure provided 3h (27 mg, 57%) and 3h' (2 mg, 4%) as colorless
cm
1250, 1178, 1033, 979, 923, 835, 756; H NMR (400 MHz, CDCl
) n 3079, 3006, 2954, 2838, 1751, 1726, 1641, 1613, 1516, 1304,
1
3
)
ꢀ
1
oils. 3h: IR (neat, cm
435, 1228, 1144, 1073, 995, 920; H NMR (500 MHz, CDCl
5.89e5.80 (m, 1H), 5.78 (ddt, J ¼ 17.2, 9.7, 7.4 Hz, 1H), 5.18e5.07
)
n
3079, 2979, 2953, 2927, 1752, 1730, 1642,
d
7.38 (d, J ¼ 8.8 Hz, 2H), 6.90 (d, J ¼ 8.8 Hz, 2H), 5.88e5.78 (m, 1H),
1
1
d
3
)
5.19 (ddd, J ¼ 17.4, 3.2, 1.4 Hz, 1H), 5.14 (ddd, J ¼ 10.0, 1.8, 1.0 Hz, 1H),
4.92 (dd, J ¼ 11.0, 3.0 Hz, 1H), 3.81 (s, 3H), 3.76 (s, 3H), 2.86 (d,
J ¼ 7.6 Hz, 2H), 2.78 (ddd, J ¼ 17.6, 6.0, 3.2 Hz, 1H); 2.63 (ddd,
(
m, 4H), 3.92 (ddt, J ¼ 10.3, 6.3, 4.0 Hz, 1H), 3.76 (s, 3H), 2.80 (ddt,
13
J ¼ 14.3, 7.4, 1.1 Hz, 1H), 2.73 (ddt, J ¼ 14.3, 7.4, 1.1 Hz, 1H), 2.67 (ddd,
J ¼ 16.9, 6.0, 4.6 Hz,1H), 2.51 (dtt, J ¼ 14.2, 6.3, 1.1 Hz,1H), 2.45 (ddd,
J ¼ 16.9, 10.3, 7.4 Hz, 1H), 2.32 (ddt, J ¼ 14.2, 7.4, 6.3 Hz, 1H),
J ¼ 17.4, 11.0, 6.8 Hz, 1H), 2.46e2.35 (m, 1H), 2.27e2.21 (m, 1H);
C
NMR (100 MHz, CDCl
3
) d 205.2, 169.2, 159.4, 133.0, 131.5, 127.5,
119.6, 113.9, 87.1, 74.3, 55.3, 52.9, 37.9, 36.4, 31.0. HRMS (EI) m/z
.10e1.95 (m, 2H); 13C NMR (125 MHz, CDCl
)
d
205.6, 169.0, 134.0,
þ
2
3
20 5
calcd for C17H O (M) 304.1311, found 304.1352.
1
31.4, 119.4, 117.5, 87.1, 72.1, 52.8, 40.1, 37.5, 35.6, 28.5; HRMS (FAB)
m/z calcd for C13
H
19
O
4
(M þ H)þ 239.1283, found 239.1288.
4.3. Synthesis of (þ)-tanikolide (1)
4
2
.2.8. rel-(2R,6S)-Methyl 2-allyl-6-phenyl-3-oxotetrahedropyran-
-carboxylate (3i)
4.3.1. (S)-4-Allyloxy-5-(tert-butyldimethylsilyloxy)pent-1-yl
acetate (10)
Rh(II)-catalyzed oxonium ylide formatione[2,3]-sigmatropic
Allyl bromide (2.7 mL, 31.0 mmol), Ag
2
O (3.59 g, 15.5 mmol), and
rearrangement of 2i (61 mg, 0.20 mmol) according to the typical
procedure provided 3i (47 mg, 85%) as a colorless oil: IR (neat,
CaSO (2.81 g, 20.7 mmol) were added to a solution of (S)-5-(tert-
butyldimethylsilyloxy)-4-hydroxypent-1-yl acetate (9) [16] (2.14 g,
7.75 mmol) and MS4A (2.14 g) in toluene (31 mL) at room temper-
4
ꢀ
1
cm
281, 1227, 1143, 1110, 1065, 995, 980, 924; H NMR (400 MHz,
CDCl 7.48e7.45 (m, 2H), 7.39e7.36 (m, 2H), 7.33e7.29 (m, 1H),
)
n
3066, 3030, 2953, 2928, 1752, 1725, 1641, 1496, 1456, 1437,
1
1
ature under N
15.5 mmol) and CaSO
reaction mixture and the mixture was stirred for 2 days. After
further addition of Ag O (3.59 g, 15.5 mmol) and CaSO (2.81 g,
2
in the dark. After stirring for 2 days, Ag
2
O (3.59 g,
3
)
d
4
(2.81 g, 20.7 mmol) were added again to the
5
1
2
1
2
.86e5.78 (m, 1H), 5.20 (ddd, J ¼ 17.0, 3.2, 1.6 Hz, 1H), 5.16e5.13 (m,
H), 4.97 (dd, J ¼ 11.4, 3.0 Hz, 1H), 3.80 (s, 0.19H, minor), 3.76 (s,
.81H, major), 2.87 (d, J ¼ 7.3 Hz, 2H), 2.79 (ddd, J ¼ 17.2, 6.0, 3.2 Hz,
H), 2.64 (ddd, J ¼ 17.4, 11.2, 6.8 Hz, 1H), 2.45e2.34 (m, 1H),
2
4
20.7 mmol), the mixture was stirring for further 2 days. The reac-
tion mixture was filtered through the pad of Celite. The filtrate was
concentrated in vacuo, and the residue was purified by column
chromatography (silica gel, 10% EtOAc in hexane) to provide allyl
ether 10 (1.29 g, 55%, 92% brsm) as a colorless oil and unreacted
.31e2.26 (m, 1H); 13C NMR (100 MHz, CDCl
) d 205.0, 169.0, 140.9,
3
1
31.4, 128.5, 128.0, 126.0, 119.7, 87.4, 74.5, 52.9, 37.9, 36.3, 31.2;
þ
HRMS (EI) m/z calcd for C16
18 4
H O (M) 274.1205, found 274.1215.
2
0
alcohol 9 (927 mg, 43%) was recovered. 10: [
a
]
D
ꢀ 20.8 (c 1.0,
2955, 2930, 2858, 1742, 1246, 1101, 838,
777; H NMR (500 MHz, CDCl
5.91 (ddt, J ¼ 17.2,10.3, 5.7 Hz,1H),
ꢀ
1
4.2.9. rel-(2R,6S)-Methyl 2-allyl-6-(4-fluorophenyl)-3-
CHCl
3
); IR (neat, cm
) n
1
oxotetrahedropyran-2-carboxylate (3j)
3
) d
Rh(II)-catalyzed oxonium ylide formatione[2,3]-sigmatropic
rearrangement of 2j (64 mg, 0.20 mmol) according to the typical
procedure provided 3j (40 mg, 68%) as a colorless oil: IR (neat,
5.26 (dd, J ¼ 17.2, 1.7 Hz, 1H), 5.15 (d, J ¼ 10.3 Hz, 1H), 4.16 (dd,
J ¼ 12.6, 5.2 Hz, 1H), 4.16 (dd, J ¼ 12.6, 5.2 Hz, 1H), 4.08 (t, J ¼ 6.3 Hz,
2H), 4.02 (dd, J ¼ 12.6, 5.7 Hz, 1H), 3.66 (dd, J ¼ 10.3, 5.7 Hz, 1H),
3.53 (dd, J ¼ 10.3, 5.7 Hz, 1H), 3.40e3.35 (m, 1H), 2.04 (s, 3H),
1.84e1.75 (m, 1H), 1.72e1.56 (m, 2H), 1.52e1.44 (m, 1H), 0.89 (s,
ꢀ
1
cm
436, 1415, 1296, 1281, 1225, 1158, 1074, 996, 981, 924, 837; H NMR
400 MHz, CDCl
7.44 (dd, J ¼ 7.8, 5.4 Hz, 2H), 7.06 (t, J ¼ 8.6 Hz,
H), 5.87e5.76 (m, 1H), 5.19 (dd, J ¼ 17.6, 1.2 Hz, 1H), 5.15 (d,
) n 3079, 3015, 2955, 2930, 2854, 1751, 1726, 1642, 1608, 1512,
1
1
(
2
13
3
)
d
3
9H), 0.06 (s, 6H); C NMR (125 MHz, CDCl ) d 171.2, 135.3, 116.7,
79.2, 71.3, 65.4, 64.6, 28.1, 25.9, 24.6, 21.0, 18.3, ꢀ5.38, ꢀ5.44; HRMS
J ¼ 10.4 Hz, 1H), 4.95 (dd, J ¼ 11.6, 3.1 Hz, 1H), 3.79 (s, 0.5H, minor),
(FAB) m/z calcd for C16
H O
33 4
Si (M þ H)þ 317.2148, found 317.2140.
3
3
.77 (s, 2.5H, major), 2.86 (d, J ¼ 6.8 Hz, 2H), 2.78 (ddd, J ¼ 17.7, 5.7,
.1 Hz, 1H), 2.63 (ddd, J ¼ 17.6, 11.2, 6.4 Hz, 1H), 2.41e2.23 (m, 2H);
4.3.2. (S)-4-Allyloxy-5-(tert-butyldimethylsilyloxy)pentan-1-ol
(18)
1
3
C NMR (100 MHz, CDCl
3
)
d
204.7, 163.7, 162.4 (d, J ¼ 246 Hz),
1
5
2
36.8,131.3,127.8 (d, J ¼ 8.5 Hz),119.7,115.3 (d, J ¼ 22 Hz), 87.3, 74.0,
K
2
CO
3
(756 mg, 5.47 mmol) was added to a solution of acetate 10
F (M þ H)þ
(1.37 g, 4.56 mmol) in MeOH (46 mL) at 0 C under N
ꢁ
. After stirred
2.9, 38.0, 36.2, 31.1; HRMS (FAB) m/z calcd for C16
H
17
O
4
2
92.1111, found 287.1117.
for 5 h, the reaction mixture was evaporated. The residue was
Please cite this article as: H. Jinnouchi et al., Chemo- and stereoselective six-membered oxonium ylide formatione[2,3]-sigmatropic
rearrangement of 2-diazo-3-ketoesters with dirhodium(II) catalyst and its application to the synthesis of (þ)-tanikolide, Tetrahedron,
https://doi.org/10.1016/j.tet.2019.03.012

H. Jinnouchi et al. / Tetrahedron xxx (xxxx) xxx
7
dissolved in water (30 mL) and extracted with EtOAc (3 ꢂ 20 mL).
The combined organic layer was dried over anhydrous Na SO . The
4.3.5. (S)-Methyl 6-allyloxy-7-tert-butyldimethylsilyloxy-2-diazo-
3-oxoheptanoate (2m)
2
4
filtrate was concentrated in vacuo, and the residue was purified by
A solution of p-ABSA (718 mg, 2.99 mmol) in CH
3
CN (7 mL) and
column chromatography (silica gel,15% EtOAc in hexane) to provide
Et
3
N (0.69 mL, 4.98 mmol) was added dropwise to a solution of
2
0
ꢁ
1
8 (1.15 g, 92%) as a colorless oil: [
a
]
D
ꢀ 21.3 (c 1.0, CHCl
3
); IR (neat,
ketoester 11 (858 mg, 2.49 mmol) in CH
N . After stirring at room temperature for 5.5 h, the reaction
2
3
CN (24 mL) at 0 C under
ꢀ
1
1
cm
)
n
3389, 2952, 2929, 2858, 1254, 1095, 837, 776; H NMR
(
(
(
(
500 MHz, CDCl
3
)
d
5.92 (dddd, J ¼ 17.2, 10.1, 6.0, 5.5 Hz, 1H), 5.27
mixture was evaporated. The residue was dissolved in ether
ddd, J ¼ 17.2, 3.2, 1.4 Hz, 1H), 5.16 (ddd, J ¼ 10.1, 3.0, 1.4 Hz, 1H), 4.19
ddt, J ¼ 12.4, 5.5, 1.4 Hz,1H), 4.04 (ddt, J ¼ 12.4, 6.0,1.4 Hz,1H), 3.68
dd, J ¼ 10.5, 5.5 Hz, 1H), 3.65 (dd, J ¼ 11.4, 5.5 Hz, 2H), 3.55 (dd,
(30 mL), and washed with 10% aqueous KOH (2 ꢂ 15 mL) water
2 4
(15 mL) and brine (15 mL), and dried over anhydrous Na SO . The
filtrate was concentrated in vacuo, and the residue was purified by
column chromatography (silica gel,10% EtOAc in hexane) to provide
J ¼ 10.5, 5.5 Hz, 1H), 3.44e3.38 (m, 1H), 1.99 (t, J ¼ 6.0 Hz, 1H),
2
0
1
.73e1.63 (m, 3H), 1.57e1.50 (m, 1H), 0.90 (t, J ¼ 2.7 Hz, 9H), 0.06 (t,
2m (902 mg, 98%) as a yellow oil: [
a]
D
ꢀ 18.6 (c 1.0, CHCl
3
); IR
1
3
ꢀ1
J ¼ 3.2 Hz, 6H); C NMR (125 MHz, CDCl
3
)
d
135.1, 116.9, 79.7, 71.3,
(neat, cm
)
n
2955, 2930, 2858, 2135, 1726, 1659, 1310, 1127, 1087,
5.90 (ddt, J ¼ 17.2, 10.3,
5.7 Hz, 1H), 5.25 (d, J ¼ 17.2 Hz, 1H), 5.14 (d, J ¼ 10.3 Hz, 1H), 4.14
1
6
5.3, 63.0, 28.7, 28.3, 25.9, 18.3, ꢀ5.37, ꢀ5.43; HRMS (FAB) m/z calcd
3
838, 777; H NMR (500 MHz, CDCl ) d
for C14
H
31
O
3
Si (M þ H)þ 275.2043, found 275.2038.
(
3
3
dd, J ¼ 12.6, 5.2 Hz, 1H), 4.01 (dd, J ¼ 12.6, 5.7 Hz, 1H), 3.83 (s, 3H),
.67 (dd, J ¼ 10.3, 5.7 Hz, 1H), 3.55 (dd, J ¼ 10.3, 5.1 Hz, 1H),
.44e3.40 (m, 1H), 3.02e2.89 (m, 2H), 1.96e1.89 (m, 1H), 1.77 (dt,
4
.3.3. (S)-4-Allyloxy-5-(tert-butyldimethylsilyloxy)pentanal (19)
A solution of DMSO (0.31 mL, 4.34 mmol) in CH Cl (3.2 mL) was
2
2
13
J ¼ 14.3, 8.0 Hz, 1H), 0.89 (s, 9H), 0.06 (s, 6H); C NMR (125 MHz,
dropped to a solution of oxalyl chloride (0.24 mL, 2.89 mmol) in
CH
alcohol 18 (397 mg, 1.45 mmol) in CH
ped to the reaction mixture over 15 min. After stirring for
ꢁ
CDCl 192.6, 161.8, 135.3, 116.5, 78.9, 71.2, 65.5, 52.1, 36.2, 26.2,
3
) d
2
Cl
2
(1.5 mL) at ꢀ80 C under N
2
over 15 min. A solution of
Cl (2.5 mL) was then drop-
2
(
5.9, 18.3, ꢀ5.39, ꢀ5.44; HRMS (FAB) m/z calcd for C17
31 2 5
H N O Si
2
2
M þ H)þ 371.2002, found 371.2043.
ꢁ
3
0 min at ꢀ80 C, Et
3
N (1.0 mL, 7.23 mmol) was added to the reac-
tion mixture and the mixture was allowed to warm to room tem-
perature over 60 min. After stirred at room temperature for 30 min,
the reaction mixture was quenched by the addition of saturated
4.3.6. (2R,6S)-Methyl 2-allyl-6-(tert-butyldimethylsilyloxy)-
methyl-3-oxotetrahydropyran-2-carboxylate (3m)
A solution of diazoketoester 2m (74 mg, 0.20 mmol) in CH
(1.0 mL) was added dropwise to a solution of Rh (R-PTTL) (2.8 mg,
0.002 mmol, 1 mol%) in CH Cl (1.0 mL) at room temperature under
2
N . After stirring the reaction mixture for 3.5 h, the reaction
2 2
Cl
aqueous NH
3 ꢂ 15 mL) and combined organic layers were dried over anhy-
drous Na SO . The filtrate was concentrated in vacuo, and the
4
Cl (10 mL). The mixture was extracted with CH
2
Cl
2
2
4
(
2
2
2
4
residue was purified by column chromatography (silica gel, 8%
EtOAc in hexane) to provide 19 (354 mg, 90%), which was unstable
mixture was evaporated and the residue was purified by column
chromatography (silica gel, 10% EtOAc in hexane) to provide 3m
2
0
23
and used to next step immediately, as a colorless oil: [
a
]
D
ꢀ 30.4 (c
2954, 2929, 2858, 1726, 1472, 1256,
095, 838, 777, 759; H NMR (400 MHz, CDCl 9.77 (br s,1H), 5.88
ddt, J ¼ 16.9, 10.5, 5.5 Hz, 1H), 5.24 (dd, J ¼ 16.9, 1.4 Hz, 1H), 5.15 (d,
(61 mg, 90%, dr ¼ >48:1) as a colorless oil: [
a
]
D
þ43.4 (c 1.0, CHCl
3
);
ꢀ1
ꢀ1
1
1
.0, CHCl
3
); IR (neat, cm
)
n
IR (neat, cm
) n 2954, 2929, 2885, 2857, 1754, 1731, 1642, 1472,
1
1
3
)
d
1463, 1436, 1361, 1252, 1224, 1137, 1103, 995, 920, 839, 779; H NMR
(500 MHz, CDCl
(
3
)
d
5.78 (ddt, J ¼ 17.2, 9.7, 6.9 Hz, 1H), 5.16 (ddd,
J ¼ 10.5 Hz, 1H), 4.13 (dd, J ¼ 12.4, 5.5 Hz, 1H), 3.97 (dd, J ¼ 12.4,
J ¼ 17.2, 3.2, 1.1 Hz, 1H), 5.13 (ddt, J ¼ 9.7, 3.2, 1.1 Hz, 1H), 3.95 (dddd,
J ¼ 10.6, 6.3, 4.3, 3.4 Hz, 1H), 3.84 (dd, J ¼ 10.3, 5.1 Hz, 1H), 3.753 (s,
0.06H), 3.746 (s, 2.94H), 3.64 (dd, J ¼ 10.3, 6.3 Hz, 1H), 2.80 (ddt,
J ¼ 14.3, 6.9, 1.1 Hz,1H), 2.73 (ddt, J ¼ 14.3, 6.9, 1.1 Hz, 1H), 2.70 (ddd,
J ¼ 17.2, 6.3, 4.0 Hz, 1H), 2.46 (ddd, J ¼ 17.2, 11.2, 6.9 Hz, 1H),
2.19e2.13 (m, 2H), 2.02e1.93 (m, 1H), 0.90 (s, 1H), 0.074 (s, 3H),
5
1
4
.5 Hz, 1H), 3.68 (dd, J ¼ 10.3, 5.5 Hz, 1H), 3.53 (dd, J ¼ 10.3, 5.5 Hz,
H), 3.41e3.36 (m, 1H), 2.53 (t, J ¼ 7.3 Hz, 2H), 1.93 (ddt, J ¼ 14.5, 7.1,
.1 Hz, 1H), 1.78 (dt, J ¼ 14.5, 7.3 Hz, 1H), 0.90 (s, 9H), 0.06 (s, 6H);
1
3
C NMR (100 MHz, CDCl
3
) d 202.5, 135.0, 116.9, 78.7, 71.3, 65.1, 40.0,
2
5.9, 24.4, 18.2, ꢀ5.3, ꢀ5.4.
13
0
3
.071 (s, 3H); C NMR (125 MHz, CDCl ) d 205.5, 169.0, 131.3, 119.4,
8
6.7, 72.8, 65.7, 52.8, 37.7, 35.4, 25.8, 25.7, 18.3, ꢀ5.3, ꢀ5.4; HRMS
4
.3.4. (S)-Methyl 6-allyloxy-7-tert-butyldimethylsilyloxy-3-
(FAB) m/z calcd for C17
H
31
O
5
Si (M þ H)þ 343.1941, found 343.1912.
oxoheptanoate (11)
A solution of the methyl diazoacetate (194 mg, 1.94 mmol) in
CH
CH
2
Cl
Cl
2
(3 mL) and a solution of aldehyde 19 (353 mg, 1.30 mmol) in
(4 mL) were added to a suspension of SnCl (49 mg,
Cl (9 mL) over 20 min at room temperature
. After stirring for 6.5 h, the reaction mixture was evapo-
4.3.7. (2R,5S)-Methyl-5-(tert-butyldimethylsilyloxy)methyl-3-oxo-
2-(2-undecen-1-yl)tetrahydropyran-2-carboxylate (12)
Grubbs 2nd catalyst (2.5 mg, 0.003 mmol, 1 mol%) was added to
the solution of 3m (100 mg, 0.29 mmol) and 1-decene (0.28 mL,
2
2
2
0
.26 mmol) in CH
2
2
under N
2
rated and the residue was purified by column chromatography
3 2
1.46 mmol) in CHCl (2.9 mL) at room temperature under N . After
(
silica gel, 10% EtOAc in hexane) to provide 11 (384 mg, 86%) as a
refluxing for 3 h, Grubbs 2nd catalyst (2.5 mg, 0.006 mmol, 1 mol%)
and 1-decene (0.28 mL, 1.46 mmol) was added again to the reaction
mixture and the mixture was refluxed for 3 h. After further addition
of Grubbs 2nd catalyst (2.5 mg, 0.006 mmol, 1 mol%), the reaction
mixture was refluxed for 2.5 h. The solvent was removed in vacuo,
and the residue was purified by column chromatography (silica gel,
7% EtOAc in hexane) to provide 12 (114 mg, 86%) as a pale yellow
24
ꢀ1
); IR (neat, cm ) n
pale yellow oil: [
2
a
]
D
ꢀ 24.2 (c 1.0, CHCl
3
2954,
1
930, 2858, 1751, 1719, 1255, 1123, 1085, 838, 777; H NMR
(
400 MHz, CDCl
3
)
d
12.0 (s, 0.07H), 5.87 (ddd, J ¼ 17.4, 10.1, 5.5 Hz,
1
4
3
3
2
H), 5.24 (d, J ¼ 17.4 Hz, 1H), 5.15 (d, J ¼ 10.1 Hz, 1H), 5.01 (s, 0.07H),
.13 (dd, J ¼ 12.4, 5.5 Hz, 1H), 3.97 (dd, J ¼ 12.4, 5.5 Hz, 1H), 3.74 (s,
H), 3.65 (dd, J ¼ 10.5, 5.5 Hz, 1H), 3.53 (dd, J ¼ 10.5, 5.5 Hz, 1H),
.35 (s, 1.86H), 3.41e3.35 (m, 1H), 2.65 (t, J ¼ 7.3 Hz, 1.86H),
.38e2.25 (m, 0.14H), 1.90 (ddt, J ¼ 14.4, 7.3, 4.1 Hz, 1H), 1.71 (dt,
2
3
ꢀ1
) n
oil: [
1755, 1733, 1462, 1436, 1254, 1219, 1101, 973, 839, 778; H NMR
(500 MHz, CDCl
a]
D
þ41.5 (c 1.0, CHCl
3
); IR (neat, cm
2954, 2927, 2856,
1
13
J ¼ 14.4, 7.3 Hz, 1H), 0.89 (s, 9H), 0.06 (s, 6H); C NMR (100 MHz,
3
)
d
5.54 (dt, J ¼ 14.9, 6.9 Hz, 1H), 5.37 (dt, J ¼ 14.9,
CDCl
2
3
)
d
202.6, 167.7, 135.1, 116.8, 78.4, 71.2, 65.3, 52.3, 49.0.38.9,
6.9 Hz, 1H), 3.98e3.91 (m, 1H), 3.85 (dd, J ¼ 10.3, 5.2 Hz, 1H), 3.74
(br s, 3 H), 3.64 (dt, J ¼ 9.7, 6.9 Hz, 1H), 2.82 (dd, J ¼ 14.9, 7.5 Hz,
0.25H), 2.76e2.64 (m, 2.75H), 2.45 (ddt, J ¼ 17.5, 10.3, 6.9 Hz, 1H),
5.9, 25.5, 18.2, ꢀ5.41, ꢀ5.45; HRMS (FAB) m/z calcd for C17
33 4
H O
þ
(
M þ H) 345.2097, found 345.2086.
Please cite this article as: H. Jinnouchi et al., Chemo- and stereoselective six-membered oxonium ylide formatione[2,3]-sigmatropic
rearrangement of 2-diazo-3-ketoesters with dirhodium(II) catalyst and its application to the synthesis of (þ)-tanikolide, Tetrahedron,
https://doi.org/10.1016/j.tet.2019.03.012

8
H. Jinnouchi et al. / Tetrahedron xxx (xxxx) xxx
2
2
.17 (ddt, J ¼ 13.7, 6.3, 4.0 Hz, 1H), 2.05 (dd, J ¼ 14.0, 6.9 Hz, 0.5H),
.01e1.93 (m, 2.5H), 1.35e1.26 (m, 12H), 0.91 (br s, 6.75H), 0.90 (br
(204 mg, 0.45 mmol) in MeOH (2.2 mL) at room temperature. The
reaction mixture was placed in an autoclave and was vigorously
stirred under 10 atm of hydrogen for 2 h. The mixture was filtered
through a pad of Celite. The filtrate was concentrated in vacuo and
the residue was purified by column chromatography (silica gel, 3%
EtOAc in hexane) to provide 21 (192 mg, 96%) as a colorless oil:
13
s, 2.25H), 0.88 (t, J ¼ 6.9 Hz, 3H), 0.08 (br s, 6H); C NMR (125 MHz,
CDCl 205.83, 205.75, 169.2, 169.0, 135.8, 134.1, 122.3, 121.4, 87.1,
6.7, 72.9, 72.6, 65.74, 65.70, 52.8, 52.7, 36.6, 35.5, 32.6, 31.9, 31.8,
1.5, 29.50, 29.48, 29.42, 29.35, 29.26, 29.11, 29.07, 27.5, 25.9, 25.8,
3
) d
8
3
2
0
ꢀ1
n
2
C
5.7, 22.6, 18.28, 18.26, 14.1, ꢀ5.3, ꢀ5.4; HRMS (FAB) m/z calcd for
[
a
]
D
þ16.5 (c 1.0, CHCl
1734, 1463, 1361, 1253, 1196, 1151, 1129, 1109, 1080, 839, 779;
NMR (500 MHz, CDCl
3
); IR (neat, cm
)
2952, 2926, 2855, 1761,
þ
1
H
25 47
O
5
Si (M þ H) 455.3193, found 455.3195.
H
3
)
d
3.74 (dd, J ¼ 9.6, 5.0 Hz, 1H), 3.72 (s, 3H),
4.3.8. (2R,5S)-Methyl-5-(tert-butyldimethylsilyloxy)methyl-3-(4-
3.57 (ddt, J ¼ 8.2, 5.0, 1.8 Hz, 1H), 3.50 (dd, J ¼ 9.6, 6.4 Hz, 1H), 2.13
(ddd, J ¼ 14.1, 11.9, 4.1 Hz, 1H), 1.79e1.67 (m, 6H), 1.18e1.02 (m, 2H),
1.25 (br s, 17H), 0.89 (s, 9H), 0.88 (dd, J ¼ 8.2, 6.9 Hz, 3H), 0.071 (s,
toluenesulfonyl)hydrazinylidene-2-(2-undecen-1-yl)
tetrahydropyran-2-carboxylate (20)
p-Toluenesulfonyl hydrazide (278 mg, 1.49 mmol) was added to
a solution of ketone 12 (451 mg, 0.99 mmol) in THF (4 mL) at room
13
3
3H), 0.065 (s, 3H); C NMR (125 MHz, CDCl ) d 174.9, 78.9, 71.3,
67.0, 52.0, 32.1, 31.9, 31.3, 29.8, 29.63, 29.61, 29.59, 29.52, 29.3, 27.6,
temperature under N
tosylhydrazine (184 mg, 0.99 mmol) was added. After stirring for
h, solvent was removed in vacuo and the residue was purified by
column chromatography (silica gel, 20% EtOAc in hexane) to pro-
2
. After stirring at room temperature for 21 h,
25.9, 23.3, 22.7, 18.9, 18.4,14.1, ꢀ5.2, ꢀ5.4; HRMS (FAB) m/z calcd for
C
25
H
51
O
4
Si (M þ H)þ 443.3557, found 443.3583.
8
4.3.11. (2R,5S)-5-(tert-Butyldimethylsilyloxy)methyl-2-
undecanyltetrahydropyran-2-methanol (14)
2
3
vide 20 (567 mg, 92%) as a colorless oil: [
a
]
D
þ5.4 (c 1.0, CHCl
3
); IR
ꢀ
1
(
neat, cm
)
n
3213, 2953, 2926, 2855, 1748, 1599, 1462, 1436, 1407,
DIBAL-H (1.0 M in hexane, 1.1 mL 1.05 mmol) was added drop-
1
1343, 1254, 1215, 1169, 1094, 972, 919, 839, 814, 778, 713, 551; H
wise to a solution of methyl ester 21 (185 mg, 0.42 mmol) in CH
2
Cl
2
ꢁ
ꢁ
NMR (500 MHz, CDCl
3
)
d
7.82 (d, J ¼ 8.0 Hz, 2H), 7.50 (s, 1H), 7.31 (d,
(4.2 mL) at ꢀ40 C under N
2
. After stirring at 0 C for 10 min, the
J ¼ 8.0 Hz, 2H), 5.40 (dt, J ¼ 14.9, 6.9 Hz, 1H), 5.25 (dt, J ¼ 14.9,
reaction mixture was quenched by the addition of MeOH (2 mL)
7
2
.4 Hz, 1H), 3.76 (dd, J ¼ 9.6, 5.2 Hz, 1H), 3.69e3.63 (m, 1H), 3.61 (s,
and saturated aqueous NH
room temperature. The mixture was dried over anhydrous Na
4
Cl (1 mL) and then allowed to warm to
SO
.55H), 3.60 (s, 0.45H), 3.51 (dt, J ¼ 17.2, 7.4 Hz, 1H), 2.78 (dd,
2
4
J ¼ 14.9, 7.4 Hz, 0.15H), 2.66 (dd, J ¼ 14.0, 6.9 Hz, 0.85H), 2.59 (dd,
J ¼ 14.9, 7.4 Hz, 0.15H), 2.55 (dd, J ¼ 14.0, 6.9 Hz, 0.85H), 2.49 (ddd,
J ¼ 17.0, 5.7, 2.3 Hz, 1H), 2.43 (s, 3H), 2.18 (ddd, J ¼ 17.0, 11.7, 6.9 Hz,
and filtered through a pad of Celite. The filtrate was concentrated in
vacuo and the residue was purified by column chromatography
(silica gel, 5% EtOAc in hexane) to provide 14 (167 mg, 97%) as a
2
4
ꢀ1
) n
1
H), 2.01e1.94 (m, 1.3H), 1.91e1.84 (m, 1.7H), 1.62e1.51 (m, 2.15H),
colorless oil: [
2855, 1463, 1361, 1254, 1131, 1108, 1082, 838, 777; H NMR
(500 MHz, CDCl
a
]
D
þ6.0 (c 1.0, CHCl
3
); IR (neat, cm
3470, 2926,
1
1
6
.35e1.18 (m, 12.85H), 0.88 (t, J ¼ 6.9 Hz, 3H), 0.87 (s, 9H), 0.04 (s,
13
H); C NMR (125 MHz, CDCl
3
)
d
171.3, 154.7, 144.2, 135.1, 134.93,
3
)
d
3.61 (ddd, J ¼ 10.3, 5.2, 2.3 Hz, 1H), 3.58 (d,
134.91, 129.52, 129.45, 128.2, 128.1, 123.29, 123.27, 82.1, 73.3, 73.2,
J ¼ 12.6 Hz, 1H), 3.56 (dd, J ¼ 12.6, 10.3 Hz, 1H), 3.46 (ddd, J ¼ 11.5,
6.3, 2.3 Hz, 1H), 3.25 (dd, J ¼ 10.3, 6.3 Hz, 1H), 2.10 (br s, 1H),
1.73e1.59 (m, 5H), 1.44 (ddd, J ¼ 13.7, 11.5, 4.6 Hz, 1H), 1.25 (br s,
6
2
5.9, 65.8, 52.4, 52.3, 38.2, 32.6, 31.9, 29.6, 29.51, 29.46, 29.41, 29.29,
9.25, 29.19, 29.16, 25.94, 25.87, 25.81, 25.7, 24.1, 22.6, 22.3, 21.6,
1
C
8.3, 18.2, 14.10, 14.06, ꢀ5.4, ꢀ5.5; HRMS (FAB) m/z calcd for
18H), 1.21e1.05 (m, 2H), 0.89 (t, J ¼ 2.9 Hz, 9H), 0.88 (t, J ¼ 7.4 Hz,
þ
13
H
32 55
N
2
O
6
SSi (M þ H) 623.3550, found 623.3551.
3H), 0.05 (t, J ¼ 2.9 Hz, 6H); C NMR (125 MHz, CDCl
3
) d 75.6, 71.1,
6
8.5, 67.3, 31.9, 30.8, 30.4, 29.7, 29.64, 29.61, 29.34, 29.32, 28.4, 27.8,
4
.3.9. (2R,5S)-Methyl-5-(tert-butyldimethylsilyloxy)methyl-3,6-
25.9, 23.1, 22.7, 18.7, 18.3, 14.1, ꢀ5.2, ꢀ5.3; HRMS (FAB) m/z calcd for
dihydro-2-(2-undecen-1-yl)pyran-2-carboxylate (13)
24 51
C H O
3
Si (M þ H)þ 415.3608, found 415.3600.
Sodium cyanoborohydride (31 mg, 0.50 mmol) was added to a
solution of tosylhydrazone 20 (31 mg, 0.05 mmol) in DMF (2.5 mL)
at room temperature. After refluxing for 15 min, the reaction
4.3.12. (2R,5S)-2-(Benzyloxy)methyl-5-(tert-butyldimethylsilyloxy)
methyl-2-undecanyltetrahydropyran (22)
mixture was diluted with Et
2
O (20 mL) and washed with water
SO . The
Potassium bis(trimethylsilyl)amide (KHMDS, 0.5 M in toluene,
1.55 mL, 0.78 mmol) was added dropwise to the solution of alcohol
(
20 mL) and brine (20 mL), and dried over anhydrous Na
2
4
ꢁ
filtrate was concentrated in vacuo, and the residue was purified by
column chromatography (silica gel, 3% EtOAc in hexane) to provide
14 (161 mg, 0.39 mmol) in THF (3.9 mL) at ꢀ20 C under N
2
. After
ꢁ
stirring for 30 min at ꢀ20 C, benzyl bromide (0.092 mL,
2
5
1
cm
3 (12 mg, 55%) as a colorless oil: [
a
]
D
þ23.5 (c 1.0, CHCl
3
); IR (neat,
0.78 mmol) was added to the reaction mixture and the mixture was
ꢀ
1
ꢁ
ꢁ
)
n
2953, 2927, 2856, 1764, 1735, 1462, 1436, 1254, 1197, 1135,
allowed to warm to 0 C. After stirred at 0 C for 100 min, the re-
action mixture was quenched by the addition of saturated aqueous
1
3
1121, 1093, 971, 838, 778, 709; H NMR (500 MHz, CDCl ) d 5.94
(
6
3
ddd, J ¼ 10.0, 6.3, 2.3 Hz, 1H), 5.89e5.83 (m, 2H), 5.47 (dt, J ¼ 14.9,
Na
2
CO
3
(10 mL). The mixture was extracted with EtOAc (3 ꢂ 20 mL)
.9 Hz, 1H), 5.39 (ddd, J ¼ 14.9, 8.0, 6.3 Hz, 1H), 3.91e3.79 (m, 2H),
.71 (s, 0.54H), 3.70 (s, 2.46H), 3.59 (dt, J ¼ 8.9, 2.8 Hz, 1H), 2.67 (dd,
and combined organic layers were dried over anhydrous Na
The filtrate was concentrated in vacuo, and the residue was purified
by column chromatography (silica gel, 2% EtOAc in hexane) to
2
SO
4
.
J ¼ 14.3, 8.9 Hz, 0.18H), 2.58 (ddd, J ¼ 14.3, 6.3, 1.1 Hz, 1H), 2.49 (dd,
2
4
J ¼ 14.3, 8.0 Hz, 0.82H), 2.12e2.06 (m, 1H), 2.04e1.94 (m, 3H), 1.25
provide benzyl ether 22 (176 mg, 90%) as a colorless oil: [
a]
D
þ3.6
2926, 2854, 1459, 1361, 1253, 1117,
1086, 837, 776, 734, 697; H NMR (500 MHz, CDCl 7.37e7.31 (m,
ꢀ
1
(
0
br s, 12H), 0.90 (s, 7.38H), 0.89 (s, 1.62H), 0.88 (t, J ¼ 7.5 Hz, 3H),
(c 1.0, CHCl
3
); IR (neat, cm
) n
1
3
1
.08 (s, 5.92H), 0.07 (s, 1.08H); C NMR (125 MHz, CDCl
3
)
d
172.5,
3
) d
1
72.4, 134.8, 133.3, 128.53, 128.52, 128.48, 125.9, 123.3, 122.5, 80.3,
9.8, 69.9, 69.8, 66.12, 66.09, 52.3, 52.2, 40.2, 34.9, 32.6, 31.9, 31.8,
9.6, 29.49, 29.47, 29.35, 29.31, 29.28, 29.18, 27.16, 27.4, 27.2, 25.90,
4H), 7.29e7.24 (m, 1H), 4.56 (d, J ¼ 12.6 Hz, 1H), 4.52 (d, J ¼ 12.6 Hz,
1H), 3.60 (dd, J ¼ 9.7, 5.7 Hz,1H), 3.57e3.52 (m,1H), 3.40 (dd, J ¼ 9.7,
5.7 Hz, 1H), 3.37 (d, J ¼ 9.2 Hz, 1H), 3.20 (d, J ¼ 9.2 Hz, 1H), 1.83 (dt,
J ¼ 12.8, 2.9 Hz, 1H), 1.68e1.54 (m, 4H), 1.49e1.40 (m, 2H), 1.25 (br s,
17H), 1.17e1.02 (m, 2H), 0.883 (t, J ¼ 6.9 Hz, 3H), 0.882 (t, J ¼ 2.9 Hz,
7
2
2
C
5.88, 22.7, 18.3, 14.1, ꢀ5.3, ꢀ5.4; HRMS (FAB) m/z calcd for
þ
H
25 47
O
4
Si (M þ H) 439.3244, found 439.3218.
13
9
H), 0.04 (t, J ¼ 2.9 Hz, 6H); C NMR (125 MHz, CDCl
3
) d 138.8,
4.3.10. (2R,5S)-Methyl-5-(tert-butyldimethylsilyloxy)methyl-2-
128.4, 128.2, 127.8, 127.6, 127.4, 76.2, 75.4, 73.4, 70.5, 67.4, 31.9, 31.7,
30.3, 29.71, 29.69, 29.66, 29.64, 29.5, 29.4, 28.3, 25.9, 22.7, 22.6,18.7,
undecanyltetrahydropyran-2-carboxylate (21)
Pd/C (20 mg, 10 wt% of 13) was added to the solution of 13
18.4, 14.1, ꢀ5.2, ꢀ5.3; HRMS (FAB) m/z calcd for C31
57 3
H O Si
Please cite this article as: H. Jinnouchi et al., Chemo- and stereoselective six-membered oxonium ylide formatione[2,3]-sigmatropic
rearrangement of 2-diazo-3-ketoesters with dirhodium(II) catalyst and its application to the synthesis of (þ)-tanikolide, Tetrahedron,
https://doi.org/10.1016/j.tet.2019.03.012

H. Jinnouchi et al. / Tetrahedron xxx (xxxx) xxx
9
(
M þ H)þ 505.4077, found 505.4068.
Acknowledgments
This research was supported, in part, by a Grant-in-Aid for Sci-
entific Research (C) (Grant No. JP16K08158) from the Japan Society
for the Promotion of Science (JSPS) and JSPS Core-to-Core Program,
B. Asia-Africa Science Platforms.
4
2
.3.13. (2S,5R)-5-(Benzyloxy)methyl-5-undecanyltetrahydropyran-
-methanol (15)
TBAF (1.0 M in THF, 0.34 mL, 0.34 mmol) was added to a solution
ꢁ
of silyl ether 14 (161 mg, 0.32 mmol) in THF (3.2 mL) at 0 C under
N
2
and then the resulting mixture was stirred at room temperature.
After stirring for 3 h, the reaction mixture was diluted with EtOAc
20 mL) and washed with water (15 mL) and brine (15 mL), and
dried over anhydrous Na SO . The filtrate was concentrated in
vacuo, and the residue was purified by column chromatography
Appendix A. Supplementary data
(
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2019.03.012.
2
4
(
silica gel, 18% EtOAc in hexane) to provide alcohol 15 (121 mg, 97%)
24
ꢀ1
as a colorless oil: [
3
a
]
D
þ16.7 (c 1.0, CHCl
3
); IR (neat, cm ) n
3450,
References
1
030, 2925, 2854, 1496, 1455, 1361, 1205, 1104, 1046, 735, 698; H
[
1] (a) M.C. Pirrung, J.A. Werner, J. Am. Chem. Soc. 108 (1986) 6060e6062;
NMR (500 MHz, CDCl 7.36e7.31 (m, 4H), 7.28e7.27 (m, 1H), 4.56
3
) d
(
(
b) E.J. Roskamp, C.R. Johnson, J. Am. Chem. Soc. 108 (1986) 6062e6063;
c) G.K. Murphy, F.G. West, Org. Lett. 8 (2006) 4359e4361;
(
2
1
1
(
(
7
2
C
d, J ¼ 12.0 Hz, 1H), 4.53 (d, J ¼ 12.0 Hz, 1H), 3.63 (ddt, J ¼ 12.0, 6.9,
.9 Hz, 1H), 3.53 (dd, J ¼ 10.9, 2.9 Hz, 1H), 3.43 (dd, J ¼ 10.9, 6.9 Hz,
H), 3.37 (d, J ¼ 9.7 Hz, 1H), 3.23 (d, J ¼ 9.7 Hz, 1H), 2.20 (br s, 1H),
For reviews, see: (d) A. Padwa, M.D. Weingarten, Chem. Rev. 96 (1996)
2
23e269;
(
(
e) F.P. Marms a€ ter, F.G. West, Chem. Eur J. 8 (2002) 4346e4353;
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13
m, 3H), 1.32e1.12 (m, 19H), 0.88 (t, J ¼ 6.9 Hz, 3H); C NMR
125 MHz, CDCl 138.6, 128.5, 127.9, 127.7, 127.25, 127.19, 75.7,
3.4, 70.2, 66.5, 31.9, 31.1, 30.3, 29.72, 29.67, 29.63, 29.61, 29.56,
(g) Z. Sheng, Z. Zhang, C. Chu, Y. Zhang, J. Wang, Tetrahedron 73 (2017)
011e4022.
4
3
) d
[2] For recent examples, see: (a) K.L. Jackson, J.A. Henderson, H. Motoyoshi,
A.J. Phillips, Angew. Chem. Int. Ed. 48 (2009) 2346e2350;
(b) N. Shimada, S. Nakamura, M. Anada, M. Shiro, S. Hashimoto, Chem. Lett. 38
9.55, 29.4, 29.3, 26.9, 22.7, 18.5, 14.2; HRMS (FAB) m/z calcd for
þ
(
(
2009) 488e489;
H
25 43
O
3
(M þ H) 391.3123, found 391.3211.
c) J.S. Clark, R. Berger, S.T. Hayes, L.H. Thomas, A.J. Morrison, L. Gobbi, Angew.
Chem. Int. Ed. 49 (2010) 9867e9870;
4
.3.14. (R)-5-(Benzyloxy)methyl-5-undecanyltetrahydropyran-1-
(d) C. Stewart, R. McDonald, F.G. West, Org. Lett. 13 (2011) 720e723;
(
(
(
e) J.S. Clark, F. Labre, L.H. Thomas, Org. Biomol. Chem. 9 (2011) 4823e4830;
f) D.M. Hodgson, S. Man, Chem. Eur J. 17 (2011) 9731e9737;
g) J.S. Clark, D. Vignard, A. Parkin, Org. Lett. 13 (2011) 3980e3983;
one (17)
2
-Iodobenzamide catalyst 16 (1.5 mg, 0.004 mmol, 5 mol%), BHT
(
19 mg, 0.08 mmol) and Oxone® (208 mg, 0.34 mmol) were added
(h) J.S. Clark, R. Berger, S.T. Hayes, H.M. Senn, L.J. Farrugia, L.H. Thomas,
A.J. Morrison, L. Gobbi, J. Org. Chem. 78 (2013) 673e696;
to a solution of tetrahydrofuran-2-methanol 15 (33 mg, 0.08 mmol)
in MeNO /DMF (10:1, 0.37 mL) at room temperature. After stirring
for 22 h, the mixture was diluted with Et O (20 mL) and washed by
water (10 mL), saturated aqueous NaHCO (10 mL), and brine
10 mL), and dried over anhydrous Na SO . The filtrate was
(
(
i) J.S. Clark, G. Yang, A.P. Osnowski, Org. Lett. 15 (2013) 1460e1463;
j) J.S. Clark, G. Yang, A.P. Osnowski, Org. Lett. 15 (2013) 1464e1467;
2
2
(k) D.M. Hodgson, E. Moreno-Clavijo, S.E. Day, S. Man, Org. Biomol. Chem. 11
(
(
(
2013) 5362e5369;
l) B. Skrobo, J. Deska, Org. Lett. 15 (2013) 5998e6001;
m) J.S. Clark, F. Romiti, Angew. Chem. Int. Ed. 52 (2013) 10072e10075;
3
(
2
4
concentrated in vacuo, and the residue was purified by column
chromatography (silica gel, 10% EtOAc in hexane) to provide lactone
(n) J.S. Clark, L. Delion, L.J. Farrugia, Org. Lett. 16 (2014) 4300e4303;
o) D.M. Hodgson, S. Man, K.J. Powell, Z. Perko, M. Zeng, E. Moreno-Clavijo,
A.L. Thompson, M.D. Moore, J. Org. Chem. 79 (2014) 9728e9734.
3] T. Yakura, K. Matsui, K. Matsuzaka, M. Yamashita, Heterocycles 79 (2009)
353e358.
(
2
4
1
cm
7
7 (21 mg, 66%) as a colorless oil: [
a]
D
ꢀ 0.16 (c 1.0, CHCl
3
); IR (neat,
[
[
[
ꢀ
1
) n 3031, 2925, 2853, 1736, 1496, 1455, 1329, 1247, 1200, 1115,
1
4] T. Yakura, A. Ozono, K. Matsui, M. Yamashita, T. Fujiwara, Synlett 24 (2013)
37, 698; H NMR (500 MHz, CDCl
J ¼ 12.0 Hz,1H), 4.52 (d, J ¼ 12.0 Hz,1H), 3.47 (d, J ¼ 9.7 Hz, 1H), 3.45
d, J ¼ 9.7 Hz, 1H), 2.48 (dt, J ¼ 17.8, 6.3 Hz, 1H), 2.42 (dt, J ¼ 17.8,
3
) d 7.36e7.28 (m, 5H), 4.55 (d,
65e68.
5] H. Nambu, H. Jinnouchi, T. Fujiwara, T. Yakura, Synlett 27 (2016) 1106e1109.
(
6
1
[6] H. Jinnouchi, H. Nambu, T. Fujiwara, T. Yakura, Tetrahedron 74 (2018)
1059e1070.
[7] N. Pierson, C. Fern aꢀ ndez-García, M.A. McKervey, Tetrahedron Lett. 38 (1997)
.9 Hz, 1H), 1.99 (ddd, J ¼ 13.7, 8.0, 4.0 Hz, 1H), 1.93e1.85 (m, 1H),
13
.82e1.60 (m, 4H), 1.37e1.24 (m, 18H), 0.88 (t, J ¼ 6.9 Hz, 3H);
C
4705e4708.
3
NMR (125 MHz, CDCl ) d 171.6, 137.9, 128.4, 127.8, 127.6, 85.0, 74.2,
[
8] (a) S. Kitagaki, Y. Yanamoto, H. Tsutsui, M. Anada, M. Nakajima, S. Hashimoto,
Tetrahedron Lett. 42 (2001) 6361e6364;
7
2
3.6, 38.1, 31.9, 30.0, 29.9, 29.65, 29.61, 29.57, 29.50, 29.4, 27.9, 22.9,
(M þ H)þ
(b) H. Tsutsui, M. Matsuura, K. Makino, S. Nakamura, M. Nakajima, S. Kitagaki,
S. Hashimoto, Isr. J. Chem. 41 (2001) 283e295;
2.7, 16.8, 14.1; HRMS (FAB) m/z calcd for C24
39 3
H O
375.2899, found 375.2872.
(c) H. Tsutsui, T. Abe, S. Nakamura, M. Anada, S. Hashimoto, Chem. Pharm.
Bull. 53 (2005) 1366e1368.
[
9] (a) A.H.F. Lee, A.S.C. Chan, T. Li, Tetrahedron 59 (2003) 833e839;
4
.3.15. (þ)-Tanikolide (1)
Pd(OH) /C (4.2 mg, 20 wt% of 17) was added to the solution of 17
21 mg, 0.06 mmol) in EtOAc (1.1 mL) at room temperature. The
reaction mixture was vigorously stirred under H for 4.5 h. The
(b) C. Taillier, B. Gille, V. Bellosta, J. Cossy, J. Org. Chem. 70 (2005) 2097e2108.
2
[10] The stereochemistry of major isomer 3b was finally confirmed by the results
of the synthesis of (þ)-tanikolide (1) using the Rh
2 4
(S-PTTL) -catalyzed reac-
(
tion of 6-allyloxy-2-diazo-3-ketoester 2m.
2
[
11] D.F. Taber, R.E. Ruckle, J. Am. Chem. Soc. 108 (1986) 7686e7693.
mixture was filtered through a pad of Celite. The filtrate was
concentrated in vacuo and the residue was purified by column
chromatography (silica gel, 50% EtOAc in hexane) to provide
[12] For a recent review, see: T. Yakura, H. Nambu Tetrahedron Lett. 59 (2018)
188e202.
[13] The enantioselectivity of major isomer 3b was determined to be 9% by HPLC
analysis (column: Daicel Chiralpak IA, solvent: 9:1 hexane/ethanol, flow rate:
ꢁ
(
þ)-tanikolide (1) (16 mg, quant.) as a white solid: mp 43e44 C;
1
.0 mL/min, detection: UV 254 Nm) of the corresponding tosylhydrazone.
[14] The reaction of 2a, a substrate without C6-substituent, with 1 mol% of Rh
PTTL) in CH Cl for 2 h provided oxinium ylide formatione[2,3]-sigmatropic
rearrangement product 3a in 58% yield with no evidence of the formation of
CeH insertion product. This result suggests that Rh (S-PTTL) has a beneficial
2
4
25
[
a
]
D
þ2.9 (c 0.51, CHCl
3
) {lit [15]. [
a]
D
þ2.3 (c 0.65, CHCl
3
)}; IR (KBr,
2
(S-
ꢀ
1
4
2
2
cm
1
) n 3383, 2953, 2924, 2852, 1702, 1468, 1333, 1261, 1200, 1081,
1
049; H NMR (400 MHz, CDCl
3
) d
3.66 (d, J ¼ 11.4 Hz, 1H), 3.55 (d,
2
4
J ¼ 11.4 Hz, 1H), 2.48 (dd, J ¼ 9.4, 6.9 Hz, 2H), 2.26 (br s, 1H),
effect on the chemoselectivity of ylide formation in preference to CeH
insertion.
13
1
(
2
.95e1.59 (m, 6H), 1.26 (br s, 18H), 0.88 (t, J ¼ 6.4 Hz, 3H); C NMR
100 MHz, CDCl 171.7, 86.5, 67.5, 36.6, 31.9, 30.0, 29.8, 29.58,
9.56, 29.52, 29.4, 29.3, 26.6, 23.4, 22.7, 16.6, 14.1.
[
[
15] I.P. Singh, K.E. Milligan, W.H. Gerwick, J. Nat. Prod. 62 (1999) 1333e1335.
16] T.K. Chakraborty, R. Samanta, P.K. Kumar, Tetrahedron 65 (2009) 6925e6931.
3
) d
[17] (a) L. Caglioti, M. Magi, Tetrahedron 19 (1963) 1127e1131;
Please cite this article as: H. Jinnouchi et al., Chemo- and stereoselective six-membered oxonium ylide formatione[2,3]-sigmatropic
rearrangement of 2-diazo-3-ketoesters with dirhodium(II) catalyst and its application to the synthesis of (þ)-tanikolide, Tetrahedron,
https://doi.org/10.1016/j.tet.2019.03.012

10
H. Jinnouchi et al. / Tetrahedron xxx (xxxx) xxx
(
3
b) R.O. Hutchins, C.A. Milewski, B.E. Maryanoff, J. Am. Chem. Soc. 95 (1973)
662e3668.
18] T. Yakura, Y. Horiuchi, Y. Nishimura, A. Yamada, H. Nambu, T. Fujiwara, Adv.
Synth. Catal. 358 (2016) 869e873.
[19] T. Yakura, T. Fujiwara, H. Nishi, Y. Nishimura, H. Nambu, Synlett 29 (2018)
[
2316e2320.
Please cite this article as: H. Jinnouchi et al., Chemo- and stereoselective six-membered oxonium ylide formatione[2,3]-sigmatropic
rearrangement of 2-diazo-3-ketoesters with dirhodium(II) catalyst and its application to the synthesis of (þ)-tanikolide, Tetrahedron,
https://doi.org/10.1016/j.tet.2019.03.012