Remote stereocontrol of intramolecular rhodium carbene addition driven by a small and flexible chiral 2,4-pentanediol tether

Article abstract of DOI:10.1016/j.tet.2012.03.009

Intramolecular rhodium carbenoid additions were studied using 2,4-pentanidiol as a chiral tether between a diazo group, a precursor of the carbene, and an aromatic group to be reacted with the carbene. The reaction was designed to perform the addition at

Full text of DOI:10.1016/j.tet.2012.03.009

Tetrahedron 68 (2012) 3744e3749
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journal homepage: www.elsevier.com/locate/tet
Remote stereocontrol of intramolecular rhodium carbene addition driven
by a small and flexible chiral 2,4-pentanediol tether
*
Chun Young Im, Takashi Sugimura
Graduate School of Material Science, University of Hyogo, 3-2-1 Kohto, Kamigori, Ako-gun, Hyogo 678-1297, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Intramolecular rhodium carbenoid additions were studied using 2,4-pentanidiol as a chiral tether be-
tween a diazo group, a precursor of the carbene, and an aromatic group to be reacted with the carbene.
The reaction was designed to perform the addition at a remote position, conserving the original high
stereoselectivity appeared at additions near the tether, in addition to high regioselectivity and sufficient
reaction efficiency. Substitution on the near reaction sites, the carbene carbon and aromatic group, in the
reactant was effective to relegate the reaction site to a remote position. In the present study, two remote
Received 5 February 2012
Received in revised form 2 March 2012
Accepted 3 March 2012
Available online 16 March 2012
Keywords:
€
reactions, one dealing with CeH insertion and the other classified in Buchner reaction, were found to
Rhodium carbene
Intramolecular addition
Chiral tether
give sole products in high yields.
Ó 2012 Elsevier Ltd. All rights reserved.
Remote stereocontrol
1. Introduction
The stereocontrollability of the (20R,40S)-PD tether has been
extended to the reaction with o-methyl substrate 3a, where the
Intramolecular reaction has a notable advantage to realize de-
sired reaction-selectivities.1 Chiral tethered reaction is one of the
examples, and intramolecular reactions with a chiral flexible 2,4-
pentanediol (PD) tethering a reagent to a prochiral reactant ex-
hibit strict stereocontrollability and wide applicability.2,3 Repre-
methyl should be positioned avoiding the repulsion with 40-H, and
therefore, the original reaction site of 1,2-position guided by the
tether chirality is covered by the o-methyl substituent (in Scheme 2,
C).8 In fact, an unexpected remote addition at 4,5-position is arisen
to give 4a, stereoselectively but in a low yield (29%).7 In this re-
action, when the carbene has a more electrophilic Rh2(OCOCF3)4
unit instead of Rh2(OAc)4, the reaction at the tether-guided but
sterically congested 1,2-position becomes predominant to give 5a
as a sole product (75% yield). It should be noted that the reaction at
the sterically less hindered 1,6-position of 3a is always prohibited
by the tether chirality. The geometrical arrangement C with the
(20R,40S)-PD tether has been confirmed with o-hydroxy substrate
6a. The generated carbene from 6a places close to the intrinsically
reactive acidic OH group and thus the OH insertion to give 7a is only
a detectable intramolecular reaction irrespective of the catalyst
used.9,10 In a diastereomeric process, 6b gives a remote adduct 8b in
5% yield in addition to OH insertion product 7b (17%). With a more
reactive Rh2(OCOCF3)4 carbene, 8b (42%) and 9b (40%) are pro-
duced as major products overcoming the intrinsically high re-
activity to give 7b (9%). The selectivities with 6b could be
rationalized with the arrangement D, analogous to B.
€
sentative examples are those demonstrated for Buchner reaction,
which is synthetically useful to prepare an optically active cyclo-
heptatriene skeleton (tropilidene) in one step from a phenyl moi-
ety.4,5 A rhodium carbene generated from 1a having (20R,40S)-PD
tether with Rh2(OAc)4 predominantly adds to the internal phenyl
ring at a contiguous 1,2-position to give stereochemically pure 2a in
a quantitative yield (>99% diastereomeric excess¼de, Scheme 1).6
€
Notable property of the PD-tethered Buchner reaction is that use
of a diastereomeric (20S,40S)-tether (1b) also shows moderately
high reverse-stereoselectivity to give 92% de of 2b in a high yield
(95%).7 Since effective molarity for the reaction with 1a is twice
larger than that with 1b, two methyl-groups on the PD tether are
considered to be matched in 1a and unmatched in 1b in their
stereochemical controls. Alternatively, the stereoselectivity could
be understood by geometrical arrangement; the 40-Me group fixes
the conformation of the phenyl ring, and 20-Me group regulates
geometry of the carbene to differentiate stereotopos of the phenyl
ring (in Scheme 1, A vs B).
These reported results suggest that the PD tether has surplus
stereocontrol power to perform highly stereoselective carbene
additions near the chiral tether, and extension will be possible to
the reaction at a remote position (away from the tether).11 Here, in
addition to the high stereoselectivity, high product yields need
regioselectivity and efficiency for the intramolecular reaction. In
* Corresponding author. Tel.: þ81 791 58 0168; fax: þ81 791 58 0115; e-mail
address: sugimura@sci.u-hyogo.ac.jp (T. Sugimura).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.03.009

C.Y. Im, T. Sugimura / Tetrahedron 68 (2012) 3744e3749
3745
4'S 2'R
N2
N2
O
O
O
O
O
Rh2(OAc)4
Rh2(OAc)4
S
1O O
O
O
O
O
O
O
O
O
2
(>99% yield)
(95% yield)
Rh2(OAc)4
O
1a
2a (99%de)
A
4'S 2'S
(AcO)4Rh2
O
O
O
R
O O
O
O
O
B
2b (92%de)
1b
Scheme 1.
5
4
O
O
N2
O
O
O
4'
O O
Rh2L4
O O
O
+
or
O
O
O
O
O
R
O
O
7a
Rh2L4
R
5a (>98%de)
4a (>98%de)
C
3a. R = CH3
6a. R = OH
29%
1%
L = OAc
100%
0%
75%
= OCOCF3
O
(AcO)4Rh2
O
O
O
N2
OH HO
Rh2L4
O
O O
+
7b
+
O
O
O
O
OH
6b
OH
8b (>98%de)
D
9b (>98%de)
L = OAc
17%
9%
5%
0%
= OCOCF3
42%
40%
Scheme 2.
€
this report, we would like to present Buchner and CeH insertion
reactions focusing on the extension of the addition positions, from
near to far, to obtain new stereochemically pure compounds and to
demonstrate usefulness of the PD-tether in asymmetric synthesis.12
To accomplish such the reactions, the near reaction sites were
sterically blocked by substitution on the carbene carbon and/or
aromatic carbon.
fortunate improvement from the reaction of 1b to 2b (92% de) is
explainable as follows. If conformation of the phenyl moiety is fixed
by the 40-Me sufficiently, the stereoisomer of 2b in the reaction of
1b should be formed by incomplete regulation of the carbene unit
by the 20-Me group on the tether. Basing on this hypothesis, for-
mation of epi-10b ((S)-10b) should be suppressed by the steric
fence at the reaction site with the 2-methyl substituent. Phenyl-
substituted 11b showed similar product distribution, and again,
formation of 1,6-adduct 14b was quantitative with Rh2(OCOCPh3)4
(Scheme 3, bottom). Stereochemistries of 10b and 14b, and those of
4b and 13b, were assigned to be the same by NOE signals on their
1H NMR spectra.
2. Results and discussion
2.1. Substitution on phenyl at o-position
The study was started with 3b, a diastereomer of 3a, to disclose
more about the stereocontrollability of (20R,40S)-PD tether
(Scheme 3). As expected from the geometrical arrangement D
(Scheme 2) and the experimental results with 6b, the reaction with
3b mainly underwent at the less hindered 1,6-position. However,
the yield of 10b was low (48%, NMR yield with a reference) and
remote adduct 4b was also produced (2%).13 The 2-methyl sub-
stitution slightly reduced the efficiency of the addition observed
with 1b. The low yield due to less efficiency was improved by the
use of Rh2(OCOCF3)4 to result in 91% yield of 10b. The incomplete
regioselectivity forming 4b in 7% was further improved by using
Rh2(OCOCPh3)4; sterically bulky but effective catalyst for intra-
molecular reactions,14 to result in quantitative formation of 10b.
Irrespective of the catalyst used, no diastereomer of 10b was
detected at all (<1%) to result in a high product de (>98%). This
As expected from the carbene geometry C, the reaction of 11a
at the near 1,2-position was completely blocked and the 1,2-
adduct was not produced with any catalyst. From less electro-
philic carbenes generated with Rh2(OAc)4 or Rh2(OCOCPh3)4,
a small amount of the remote 4,5-adduct 13a was obtained.15
Notable difference was observed with Rh2(OCOCF3)4 catalyst;
a generated more electrophilic carbene attacked a less electron
rich but spatially close phenyl substituent to give 12a in a high
yield (>80%). The produced 12a was a mixture of isomers, which
have four 1,2-disubstituted phenyl protons (
five olefinic protons of cycloheptatrienes instead of those for the
o-phenyl group ( 7.5, 2H; 7.4, 2H; 7.0, 1H). Thus, the addition
d 7.3, 3H; 7.0, 1H), and
d
should occur only at the phenyl substituent, and this remote
€
Buchner addition was refined by addressing luck of the selectiv-
ities remained (vide infra).16

3746
C.Y. Im, T. Sugimura / Tetrahedron 68 (2012) 3744e3749
N2
N2
O
O
O
O
O
Rh L
O O
O O
15a
OMe
OMe
2
4
+
O
COOMe
Rh2L4
O
O
O
O
O O
E
3b
10b
4b
2%
7%
0%
L = OAc
= OCOCF3
= OCOCPh3 >99%
48%
91%
COOMe
O
N2
Rh2L4
O
Rh L
2 4
O O
15b
O O
O
F
N2
O O
O
O
O
O
O O
+
O
Ph
O O
+
O
O
O
O
COOMe
13a
12a
0%
>80%
0%
11a
COOMe
17b
L = OAc
= OCOCF3
= OCOCPh3
5%
<10%
15%
16b (86: 14)
L = OCOCF3
62%
13%
Scheme 4.
synthetic purpose. Instead, inertness of 15a invented new reactions
as shown in next.
N2
O
O
O
O O
O
Ph
+
Ph
O
O
O
2.3. Substitution at both the phenyl and the diazo carbon
The substrates having both methyl diazo malonate and o-
substituted phenyl were studied with (20R,40S)-PD tether, being
expected that the carbene generated with 15a cannot reach to the
11b
14b
64%
84%
13b
L = OAc
= OCOCF3
<1%
16%
0%
aromatic p-bonds, but can reach the space where the o-substituent
will be placed (in Scheme 4, E). Just as expected, the reaction of 18a
with Rh2(OCOCF3)4 gave a predominant CeH insertion at the o-
methyl group to give 19a as a sole product (>98% de) in 95% yield,
while the less electrophilic carbenes were unreactive for intra-
molecular reaction (Scheme 5).17 The stereochemistry of produced
19a was assigned to be S by NMR, which was confirmed by X-ray
crystallography (see Fig. 1). The generated chirality is potentially
isomerizable and thus the observed de value could be governed by
the thermodynamic control. However, treatment of (S)-19a with
DABCO in CDCl3 gave a mixture of (S)-19a and its R-isomer in a ratio
of 25:75 (R-rich!) after complete equilibration (5 days). Thus, the
stereoface of the carbene carbon was found to be well differentiated
in high efficiency to perform the CeH insertion reaction.
When ethyl is substituted at the o-position, two CeH bonds at
the ethyl group should be differentiated in addition to the stereo-
face of the carbene carbon. By treatment of 20a with Rh2(OCOCF3)4,
two diastereomers of 21a were obtained in 82% yield. The ratio of
the isomer was 75:25, which was partially improved to be 80:20
using Rh2(OCOC3F7)4. The stereoisomer formation is attributable to
imperfect differentiation at the ethyl CH2, and if fact, 21a was
converted to a mixture of four stereoisomers with DABCO. Selec-
tivity at the carbene carbon was assumed to be the same as the
conversion of 18a to 19a. The substrate 22a having a bulkier o-
substituent or 23a having a conformationally fixed substituent did
not afford intramolecular adducts with any catalyst.
= OCOCPh3 100%
Scheme 3.
2.2. Substitution at the diazo carbon
Diazo malonates is known to give sufficiently reactive rhodium
carbene, but steric demand for the addition is much larger than
diazo acetates.2 Diazo decomposition of 15a underwent smoothly
at room temperature, but no intermolecular adduct was obtained
(<1%) irrespective of rhodium catalyst employed (Scheme 4). The
intramolecular reaction with 15b was also unproductive when the
catalyst was Rh2(OAc)4, but the catalysis with Rh2(OCOCF3)4 per-
formed CAreH bond insertion to give 16b in 62% yield. The reaction
was regioselective, but two diastereomers were obtained in a ratio
of 86:14, in addition to 17b in 13% yield. The structures of 16b and
17b were determined by NOE, which are shown in Supplementary
data. The stereochemistry of 17b was not only the same as 4b and
13b but also the same as 4a (13a) indicating that the conformation
of the aromatic group in the substrate is common among all the
reactions. The diazo malonate substrates, 15a and 15b, were found
to have different reactivity from 1a and 1b, and the poor reactivity
at the 1,2-addition is explainable by the geometrical arrangement
of the carbenes, where steric effect by the methoxycarbonyl group
interrupts the approach of the carbene carbon to the 1,2-position.
With 15b, the CeH insertion was found to perform in the good
yield, but the stereocontrol of the chirality at the carbene carbon
during the addition is not sufficiently high to use that for the
Finally, o-phenyl-substituted substrate 24a, a malonate ana-
logue of 11a, was studied. The reaction of 24a with Rh2(OAc)4
afforded only intermolecular adducts, the same as 18a and 20a, but
the treatment with Rh2(OCOCF3)4 smoothly afforded intra-
molecular remote adduct 25a in 72% yield, the structure of which

C.Y. Im, T. Sugimura / Tetrahedron 68 (2012) 3744e3749
3747
N2
COOMe
O O
Rh2L4
95%
O O
O
O
s
O
COOMe
Rh2L4
O
O
O
COOMe
19a (>98%de)
18a
Fig. 2. Expected geometrical arrangement for the reaction of 24a.
N2
COOMe
O O
Rh2L4
82%
O O
O
s
COOMe
Et
and efficient remote additions. The CeH insertion reaction at the o-
substituent was found to be completely stereocontrolled at the
carbene carbon to result in 10-membered ring product in 95% yield
(18a with Rh2(OCOCF3)4). The produced chirality was fragile, but
the unstable isomer could be obtained stereochemically pure form.
The addition to the remote phenyl to produce 14-membered ring
was also performed. In spite of the far remote position, the reaction
was regio- and stereochemically controlled (24a with Rh2(O-
COCF3)4). It should be noted that the reaction of 11a had a low
regioselectivity, but the addition was limited within the remote
phenyl group. Hence, further introduction of a proper substituent
onto the o-phenyl group of 11a or use of heterocycles instead of the
o-phenyl substituent will make possible to produce more syn-
thetically useful chiral compounds.
21a (75:25)
20a
L = OCOCF3
N2
COOMe
N2
COOMe
O O
O O
O
O
Ph
22a
23a
Scheme 5.
4. Experimental section
4.1. General
Melting points were determined on a Yanaco melting point
apparatus. All the substrates and products were characterized by
NMR spectrometry using a JEOL-ECA-600 spectrometer at 600 MHz
for proton spectra and 150 MHz for carbon spectra, and by IR with
an FT/IR-410 spectrophotometer. High resolution MS was obtained
by a JEOL JMS-T100LC for electron spray ionization (ESI). Optical
rotations were measured on a PerkineElmer-243B polarimeter. All
dry solvents were purified by distillation over proper drying agents.
All reactions were carried out under a dry nitrogen atmosphere. X-
ray diffraction data were recorded using a Quantum CCD area de-
tector on a Rigaku AFC-7R diffractometer at room temperature.
CCDC deposition number 863754 contains the supplementary
crystallographic data for this paper. These data can be obtained free
of charge by emailing data_request@ccdc.cam.ac.uk, or by con-
tacting The Cambridge Crystallographic Data Centre, 12, Union
Road, Cambridge CB2 1EZ, UK; fax: þ44 1223 336033.
Fig. 1. Crystal structure of 19a.
was determined by NMR (Scheme 6). The reaction site is far from
the tether chirality, but no other stereoisomer was detected at all,
being addressed the luck of the selectivity in the reaction with 11a.
Once again, geometry described for the other carbenes could rea-
sonably explain the product stereochemistry (Fig. 2). The pro-
duction of norcaradiene tautomer other than cycloheptatriene was
attributable to the tether regulation; tautomerization to the
cycloheptatriene needs a longer tether.
4.2. Rhodium-catalyzed conversion from 3b to 10b
N2
COOMe
O O
Rh2L4
72%
To a solution of 3b (40 mg) in CH2Cl2 (2 ml) was added Rh2(O-
COCPh3)4 at room temperature. After stirring for 2 h, the solution
was concentrated under vacuum. The residue consisted of essen-
tially pure 10b. Purification by a silica gel chromatography column
O O
O
O
Ph
NOE
24a
L = OCOCF3
(elution with 20% ethyl acetate in hexane) gave 10b (75% isolated
COOMe
20
yield). Colorless oil; [
a
]
D
þ76.35 (c 0.55, CH2Cl2); IR (neat) 2979,
25a (>98%de)
1731, 1601, 1513, 1445, 1302, 905, 721, 667 cmꢀ1
600 MHz)
;
1H NMR (CDCl3,
Scheme 6.
d
6.50 (d, J¼11.0 Hz,1H), 6.45 (dd, J¼11.0, 4.8 Hz,1H), 6.30
(dd, J¼8.9, 4.8 Hz, 1H), 5.94 (dd, J¼8.9, 7.6 Hz, 1H), 5.13e5.07 (m,
1H), 4.57e4.52 (m, 1H), 2.35 (d, J¼7.6 Hz, 1H), 2.02 (dq, J¼14.4,
3.4 Hz, 1H), 1.85 (s, 3H), 1.90e1.84 (m, 1H), 1.33 (d, J¼6.2 Hz, 3H),
3. Conclusion
1.27 (d, J¼6.2 Hz, 3H); 13C NMR (CDCl3, 150 MHz)
d 172.13, 138.01,
133.37, 125.74, 124.97, 119.12, 112.46, 70.13, 69.24, 46.53, 46.47,
21.30, 16.11; HRMS (ESI) m/z (MþNaþ) calcd for C14H18NaO3
257.1154, found 254.1153.
€
The original PD-tethered stereocontrolled Buchner reactions
with 1a and 1b were successfully extended to the regioselective

3748
C.Y. Im, T. Sugimura / Tetrahedron 68 (2012) 3744e3749
4.3. Rhodium-catalyzed conversion from 11b to 14b
J¼8.2 Hz, 1H), 5.40 (m, 1H), 4.34 (m, 1H), 3.66 (m, 1H), 3.64 (s, 3H),
3.52 (d, J¼1.7 Hz, 1H), 1.99 (m, 1H), 1.64 (d, J¼7.9 Hz, 3H), 1.60 (tt,
J¼7.9, 1.4 Hz, 1H), 1.42 (d, J¼6.2 Hz, 3H), 1.30 (d, J¼6.2 Hz, 3H); 13C
To a solution of 11b (58 mg) in dry CH2Cl2 (4 ml) was added
dropwise to Rh2(OCOCPh3)4 in CH2Cl2 (3 ml) at room temperature.
After stirring at room temperature for 3 h, the solution was con-
centrated under vacuum to give essentially pure 14b. The residue
was purified by silica gel chromatography column (elution with 20%
ethyl acetate in hexane) to give 14b (85% isolated yield). Pale yellow
NMR (CDCl3, 150 MHz)
d 169.86, 169.28, 157.87, 132.65, 129.76,
128.31, 120.27, 111.86, 74.90, 69.63, 57.29, 52.14, 43.53, 31.12, 22.44,
21.09, 19.79. Compound 16b: (6% isolated yield): colorless oil, IR
(neat) 2979, 1747, 1600, 1584, 1492, 1454, 1380, 1261, 1026, 910, 789,
761, 687, 666 cmꢀ1
;
1H NMR (CDCl3, 600 MHz)
d
7.26 (td, J¼8.2,
oil; [
a]
20 þ185.31 (c 0.52, CH2Cl2); IR (neat) 2980, 1731, 1587, 1493,
1.7 Hz, 1H), 7.10 (dd, J¼8.2, 1.0 Hz, 1H), 7.09 (dd, J¼7.6, 1.7 Hz, 1H),
6.98 (td, J¼7.6, 1.0 Hz, 1H), 5.30 (m, 1H), 4.56 (s, 1H), 4.40 (m, 1H),
3.75 (s, 3H), 2.15 (ddd, J¼15.1, 6.9, 4.1 Hz, 1H), 1.56 (dq-like, J¼15.1,
2.4 Hz, 1H), 1.53 (d, J¼6.2 Hz, 3H), 1.16 (d, J¼6.2 Hz, 3H); 13C NMR
D
1444, 1306, 1045, 907, 857, 761, 633 cmꢀ1
;
1H NMR (CDCl3,
600 MHz)
d
7.31 (td, J¼7.6, 1.4 Hz, 2H), 7.27 (dd, J¼8.2, 1.4 Hz, 2H),
7.22 (tt, J¼7.6,1.4 Hz,1H), 6.68e6.63 (m, 2H), 6.43 (dd, J¼8.9, 4.8 Hz,
1H), 6.01 (dd, J¼8.9, 6.9 Hz, 1H), 5.47e5.42 (m, 1H), 4.58e4.53 (m,
1H), 2.54 (d, J¼6.9 Hz, 1H), 2.21 (tdd, J¼12.4, 3.4, 1.4 Hz, 1H), 1.94
(ddd, J¼12.4, 3.4, 1.4 Hz,1H), 1.43 (d, J¼6.2 Hz, 3H), 1.12 (d, J¼6.2 Hz,
(CDCl3, 150 MHz)
d 170.03, 168.48, 157.56, 130.70, 129.35, 126.72,
122.61, 118.57, 77.45, 68.57, 55.31, 52.67, 37.66, 22.27, 19.74; HRMS
(ESI) m/z (MþNaþ) calcd for C15H18NaO5 301.1052, found 301.1062.
3H); 13C NMR (CDCl3, 150 MHz)
d
171.82, 139.04, 138.33, 132.22,
Compound 17b: (1% isolated yield): pale yellow oil; [
0.23, CH2Cl2); IR (neat) 2925,1739,1621,1435,1380,1262, 1107, 906,
a
]
20 ꢀ26.09 (c
D
129.96, 127.82, 127.25, 126.47, 125.44, 119.64, 117.45, 70.13, 69.69,
47.00, 46.26, 21.27, 20.91; HRMS (ESI) m/z (MþNaþ) calcd for
C19H20Na O3 319.1310, found 319.1318.
734, 656 cmꢀ1; 1H NMR (CDCl3, 600 MHz)
d
6.28 (d, J¼6.2 Hz, 1H),
6.05 (dd, J¼8.9, 6.2 Hz, 1H), 6.04 (d, J¼9.6 Hz, 1H), 5.97 (d, J¼8.9 Hz,
1H), 5.93 (d, J¼9.6 Hz, 1H), 4.84 (m, 1H), 4.06 (m, 1H), 3.26 (s, 3H),
2.06 (dt, J¼15.8, 4.8 Hz, 1H), 1.14 (d, J¼6.2 Hz, 3H), 0.88 (dt-like,
J¼15.8, 2.7 Hz, 1H), 0.75 (d, J¼6.2 Hz, 3H); 13C NMR (CDCl3,
4.4. Rhodium-catalyzed reactions with diazo malonates
A solution of 18a, 20a, 24a, or 15b (200 mg) in dry CH2Cl2 (4 ml)
was added dropwise to Rh2(OCOCF3)4 in CH2Cl2 (6 ml) at room
temperature. After stirring for 14 h, the solution was concentrated
under vacuum. The residue was purified by a silica gel column
(elution with 20% ethyl acetate in hexane). Compound 19a (54%
150 MHz) d 170.47, 168.69, 159.19, 124.74, 124.55, 123.55, 120.53,
74.25, 69.06, 60.39, 52.69, 40.02, 24.20, 18.67; HRMS (ESI) m/z
(MþNaþ) calcd for C15H18NaO5 301.1052, found 301.1021.
4.5. Isomerization of 19a
isolated yield): colorless hexagonal prisms; mp¼96.8e97.8 ꢁC
20
(recrystallized from ether); [
a
]
D
þ25.87 (c 0.75, CH2Cl2); IR (KBr)
To a solution of (S)-19a (3 mg) in CDCl3 (0.5 ml) was added
a small amount of DABCO, as catalyst, in NMR tube at room tem-
perature. The mixture was kept at 60 ꢁC and monitored by 1H NMR.
After 5 days, isomer ratios became constant to be (S)-19a and (R)-
19a¼25:75.
2978, 1731, 1601, 1488, 1455, 1369, 962, 916, 835, 758, 666 cmꢀ1; 1H
NMR (CDCl3, 600 MHz)
d
7.43 (dd, J¼7.6, 1.4 Hz, 1H), 7.14 (td, J¼7.6,
1.4 Hz,1H), 6.82 (t, J¼7.6 Hz,1H), 6.76 (d, J¼7.6 Hz,1H), 5.41 (m,1H),
4.35 (m, 1H), 3.71 (dd, J¼6.2, 2.7 Hz, 1H), 3.66 (s, 3H), 3.40 (dd,
J¼13.1, 6.2 Hz, 1H), 3.07 (dd, J¼13.1, 2.7 Hz, 1H), 1.99 (dt, J¼15.1,
11.0 Hz, 1H), 1.59 (d, J¼15.1 Hz, 1H), 1.41 (d, J¼6.2 Hz, 3H), 1.28 (d,
Acknowledgements
J¼6.2 Hz, 3H); 13C NMR (CDCl3, 150 MHz)
d 169.46, 168.75, 157.30,
132.55, 128.35, 125.88, 120.29, 111.16, 75.53, 69.62, 52.10, 51.09,
43.22, 28.32, 22.36, 21.19; HRMS (ESI) m/z (MþNaþ) calcd for
C16H20NaO5 315.1208, found 315.1200; mp 99e100 ꢁC. Compound
This study was supported by Grant-in-Aid from the Japan So-
ciety for the Promotion of Science (JSPS); Contract grant number:
16350026.
25a (57% isolated yield): colorless oil; [
a]
20 ꢀ53.33 (c 0.39, CH2Cl2);
D
IR (neat) 2927, 1731, 1598, 1475, 1435, 1377, 1255, 1097, 1032, 914,
Supplementary data
843, 757, 701, 668 cmꢀ1 1H NMR (CDCl3, 600 MHz)
; d 7.32 (dd,
J¼7.6, 1.7 Hz, 1H), 7.19 (td, J¼7.9, 1.7 Hz, 1H), 7.04 (td, J¼7.6, 1.0 Hz,
1H), 6.86 (dd, J¼7.9, 1.0 Hz, 1H), 6.42 (dd, J¼8.9, 1.0 Hz, 1H),
6.28e6.25 (m, 2H), 5.03 (td, J¼13.1, 6.5 Hz, 1H), 3.79 (s, 3H),
3.77e3.72 (m, 1H), 3.54 (t, J¼6.9 Hz, 1H), 3.31 (t, J¼6.9 Hz, 1H), 2.07
(td, J¼14.4, 3.4 Hz, 1H), 1.64 (dd, J¼14.4, 8.6 Hz, 1H), 1.25 (d,
J¼6.2 Hz, 3H), 1.10 (d, J¼6.2 Hz, 3H); 13C NMR (CDCl3, 150 MHz)
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2012.03.009.
References and notes
1. (a) Issacs, N. Physical Organic Chemistry; Longman: Essex, UK, 1995, pp 643e677;
(b) Hoffmann, R. W. Angew. Chem., Int. Ed. 2000, 39, 2054e2070.
d
172.55, 166.52, 155.01, 136.83, 133.33, 128.95, 128.59, 123.55,
123.36, 122.69, 121.80, 74.95, 70.25, 53.26, 45.49, 20.97, 19.67;
HRMS (ESI) m/z (MþNaþ) calcd for C21H22NaO5 377.1365, found
377.1369.
For 21a, 16b, and 17b, the products were further purified by
MPLC (Merck Lowber column, elution with 20% ethyl acetate in
hexane). Major isomer of 21a (21% isolated yield): pale yellow oil; IR
(neat) 2977, 1731, 1600, 1488, 1454, 1086, 1021, 910, 834, 744,
2. Sugimura, T. In Recent Research Developments in Organic Chemistry; Pandalai, S.
G., Ed.; Transworld Research Network: Trivandrum, 1998; Vol. 2, pp 47e53;
Sugimura, T. Eur. J. Org. Chem. 2004, 1185e1192.
3. For mechanistic analysis of the PD-tethered reactions, see: (a) Sugimura, T.;
Tei, T.; Mori, A.; Okuyama, T.; Tai, A. J. Am. Chem. Soc. 2000, 122, 2128e2129;
Sugimura, T.; Tei, T.; Okuyama, T. Tetrahedron Lett. 2003, 44, 3115e3117 and
Ref. 7; (b) Sugimura, T.; Mitani, E.; Tei, T.; Okuyama, T.; Kamiya, K.; Matsui, T.;
Shigeta, Y. Bull. Chem. Soc. Jpn., in press; Kamiya, K.; Matsui, T.; Sugimura, T.;
Shigeta, Y. J. Phys. Chem. 2012, 116, 1168e1175.
647 cmꢀ1
;
1H NMR (CDCl3, 600 MHz)
d
7.48 (dd, J¼7.6, 1.4 Hz, 1H),
4. Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for Organic
Synthesis with Diazo Compounds; Wiley: New York, NY, 1998, Chapter 6.
7.15 (m, 1H), 6.94 (t, J¼7.6 Hz, 1H), 6.76 (d, J¼8.2 Hz, 1H), 5.40 (m,
1H), 4.35 (m, 1H), 4.02 (m, 1H), 3.68 (d, J¼4.5 Hz, 1H), 3.62 (s, 3H),
1.99 (m, 1H), 1.60 (tt, J¼7.9, 1.4 Hz, 1H), 1.47 (d, J¼7.6 Hz, 3H), 1.41 (d,
J¼6.2 Hz, 3H), 1.27 (d, J¼6.2 Hz, 3H); 13C NMR (CDCl3, 150 MHz)
€
5. Doyle, M. P. In Metal Carbenes in Organic Synthesis; Dotz, Ed.; Springer: Berlin,
2004; pp 204e222; Modern Rhodium-Catalyzed Organic Reactions; Evans, P. A.,
Ed.; Wiley-VCH: Verlag, 2005.
6. Sugimura, T.; Nagano, S.; Tai, A. Chem. Lett. 1998, 45e46.
7. Sugimura, T.; Hagiya, K.; Sato, Y.; Tei, T.; Tai, A.; Okuyama, T. Org. Lett. 2001, 3,
37e40; Tei, T.; Sato, Y.; Hagiya, K.; Tai, A.; Okuyama, T.; Sugimura, T. J. Org. Chem.
2002, 67, 6593e6598.
8. For meta-substituted reactions, see: Sugimura, T.; Kagawa, M.; Ohuchi, N.;
Hagiya, K.; Okuyama, T. Bull. Chem. Soc. Jpn. 2005, 78, 671e676; See Ref. 14b;
Sugimura, T.; Kagawa, M.; Hagiya, K.; Okuyama, T. Chem. Lett. 2002, 260e261.
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d
168.82, 167.96, 156.50, 129.67, 128.86, 127.98, 120.01, 110.94, 75.45,
69.73, 56.54, 51.59, 43.53, 31.12, 22.35, 21.20, 17.09; HRMS (ESI) m/z
(MþNaþ) calcd for C17H22NaO5 329.1365, found 329.1413. minor
isomer of 21a: pale yellow oil; 1H NMR (CDCl3, 600 MHz)
d 7.34 (dd,
J¼7.6, 1.4 Hz, 1H), 7.15 (m, 1H), 6.85 (t, J¼7.6 Hz, 1H), 6.76 (d,

C.Y. Im, T. Sugimura / Tetrahedron 68 (2012) 3744e3749
3749
10. For further study on the OH insertion reaction, see: Im, C. Y.; Okuyama, T.;
Sugimura, T. Eur. J. Org. Chem. 2008, 285e294; Im, C. Y.; Okuyama, T.; Sugimura,
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12. For examples, see: Sugimura, T.; Im, C. Y.; Sato, Y.; Okuyama, T. Tetrahedron
2007, 63, 4027e4038; Sugimura, T.; Sato, Y.; Im, C. Y.; Okuyama, T. Org. Lett.
2004, 6, 4439e4442; Sugimura, T.; Kagawa, M.; Ohuchi, N.; Inoue, A.;
Okuyama, T. Chem. Lett. 2005, 34, 546e547; Sugimura, T.; Nishida, F.; Tei, T.;
Morisawa, A.; Tai, A.; Okuyama, T. Chem. Commun. 2001, 2180e2181.
13. The low efficiency of the intramolecular reactions easily caused intermolecular
reactions with external diazo group or aromatic group in addition to with
solvent and contaminated water. These byproducts could be detected by MS
spectra of the reaction mixture.
14. (a) Hashimoto, S.; Watanabe, N.; Ikegami, S. Tetrahedron Lett. 1992, 33,
2709e2712; Hashimoto, S.; Watanabe, N.; Ikegami, S. J. Chem. Soc., Chem.
Commun. 1992, 1508e1510; (b) Sugimura, T.; Ohuchi, N.; Kagawa, M.; Hagiya,
K.; Okuyama, T. Chem. Lett. 2004, 33, 404e405.
15. Stereochemistry of 13a was not fully determined, but the 1H NMR spectrum
pattern was very similar to that of 4a.
16. Use of amidate catalyst Rh2(cap)4 did not result in any intramolecular products
both with 11a and 11b.
17. Synthetic precursors of 3a and 11a have a similar diazo acetoacetate structure
to 18a and 24a, but they were inert for the intramolecular reactions.