Axially chiral dicarboxylic acid catalyzed asymmetric semipinacol rearrangement of cyclic β-hydroxy-α-diazo esters

Article abstract of DOI:10.1016/j.tet.2012.06.033

The development of axially chiral dicarboxylic acid catalyzed desymmetrizing asymmetric semipinacol rearrangement of symmetrically substituted six-membered cyclic β-hydroxy-α-diazo esters is reported as a means to give chiral cycloheptanones with good ena

Full text of DOI:10.1016/j.tet.2012.06.033

Tetrahedron 68 (2012) 7630e7635
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Axially chiral dicarboxylic acid catalyzed asymmetric semipinacol rearrangement
of cyclic b-hydroxy-a-diazo esters
*
Takuya Hashimoto, Shingo Isobe, Cedric K.A. Callens, Keiji Maruoka
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The development of axially chiral dicarboxylic acid catalyzed desymmetrizing asymmetric semipinacol
rearrangement of symmetrically substituted six-membered cyclic -hydroxy- -diazo esters is reported
as a means to give chiral cycloheptanones with good enantioselectivities.
Received 2 March 2012
Received in revised form 31 May 2012
Accepted 8 June 2012
b
a
Ó 2012 Elsevier Ltd. All rights reserved.
Available online 15 June 2012
Keywords:
Chiral Brønsted acid
Rearrangement
Diazo compounds
Desymmetrization
Ring expansion
1. Introduction
We have recently established acid catalyzed asymmetric re-
actions of 4-substituted cyclohexanones and diazo esters, wherein
desymmetrization of the 4-substituent via the diazonium in-
termediate I gives cycloheptanones having a chiral stereogenic
center (Fig. 2).3b,d,e In this context, we envisaged that it would also
be possible to generate a similar intermediate II by the protonation
Rearrangement of
b-diazonium alcohols constitutes a funda-
mental part of TiffeneaueDemjanov rearrangement (Fig. 1, (1)),1 as
well as the acid catalyzed reactions of diazo compounds with al-
dehydes or ketones (2).2e4 For the generation of this intermediate,
protonation of preformed
b
-diazo alcohols would be considered as
of symmetrically substituted cyclic b-hydroxy-a-diazo esters (cis-2)
an alternative pathway to generate the same intermediate (3). Al-
though there are some studies investigating this reaction system
with acid catalysis,5e7 its use in asymmetric catalysis has yet to be
explored.
in the presence of a chiral Brønsted acid. In conjunction with our
effort in the development of axially chiral dicarboxylic acid cata-
lyzed reactions,8 we became interested in the realization of this
plan as a novel example of chiral Brønsted acid catalyzed asym-
metric semipinacol rearrangements.9
Fig. 1. Generation of b-diazonium alcohols.
* Corresponding author. Tel./fax: þ81 (0) 75 753 4041; e-mail address: maruoka
@kuchem.kyoto-u.ac.jp (K. Maruoka).
Fig. 2. Desymmetrization via diazonium intermediates.
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.06.033

T. Hashimoto et al. / Tetrahedron 68 (2012) 7630e7635
7631
2. Results and discussion
retro-aldol process, affording ethyl diazoacetate and 4-
phenylcyclohexanone. In the next experiment, the catalyst (R)-1d
having a 3,5-di(trifluoromethyl)phenyl group gave cycloheptanone
3a in 72% yield with 34% ee (entry 4). Replacement of the ester
moiety with a tert-butyl or benzyl ester was detrimental to the
enantioselectivity (entries 5 and 6). The enantioselectivity could be
improved to 58% ee by lowering the reaction temperature to ꢀ40 ꢁC
(entry 7). This result then prompted us to develop a catalyst bearing
3,5-dinitrophenyl groups at the 3,30-position. To this end, it was
found to be necessary to develop a new synthetic scheme, which
utilizes the SuzukieMiyaura coupling of 3,30-diboryl dicarboxylic
acid ester and the corresponding aryl bromide (Scheme 1). This
strategy is complementary to the previous procedure, which uses
3,30-dibromo dicarboxylic acid ester and arylboronic acids as sub-
strates,8a,b and allowed us to access 3,5-dinitrophenyl substituted
catalyst (R)-1e in good overall yield. This catalyst was found to be
promising as cycloheptanone 3a could be obtained with 68% ee
(entry 7). The enantioselectivity could be further increased by using
toluene as solvent (entry 8). Addition of 1 equiv of water was found
to be beneficial to attain higher enantioselectivity in a reproducible
fashion (entry 10). Water is assumed to be intervening in the key
hydrogen-bonding of the substrate and the catalyst.12 On the other
hand, addition of molecular sieves had an adverse effect on the
enantioselectivity (entry 11).
As a starting point of this study, we examined several axially
chiral dicarboxylic acids (R)-1 using cis-2a as a representative
substrate (Table 1). The structure of cis-2a projecting phenyl and
diazo ester moieties in the equatorial orientation was determined
unambiguously by X-ray crystallographic analysis (Fig. 3).10 To fa-
Table 1
Optimization of the reaction conditionsa
Entry
Cat.
Solvent
Conditions [ꢁC, time]
% Yieldb
% eec
1
2
3
4
1a
1b
1c
1d
1d
1d
1d
1e
1e
1e
1e
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Toluene
Toluene
Toluene
rt, 6 h
79
67
76
72
78
73
64
63
64
62
61
26
12
4
rt, 3 min
rt, 30 min
rt, 3 min
rt, 3 min
rt, 3 min
ꢀ40, 24 h
ꢀ40, 48 h
ꢀ40, 48 h
ꢀ40, 48 h
ꢀ40, 48 h
34
25
30
58
68
74
80
71
5d
6e
7
8
9
10f
11g
a
Reactions were performed with (R)-1 (0.05 mmol), cis-2a (0.10 mmol).
Isolated yield.
Determined by chiral HPLC analysis.
tert-Butyl ester was used instead of 2a.
Benzyl ester was used instead of 2a.
H2O (0.10 mmol) was added.
Scheme 1. Synthesis of axially chiral dicarboxylic acid (R)-1e. (a) (i) Mg(TMP)2, THF;
(ii) B(OMe)3, THF, 65%; (b) 3,5-(NO2)2eC6H3Br, Pd(OAc)2, PPh3, NaHCO3, DMF, 62%; (c)
TBAF, THF, 82%.
b
c
d
e
f
With the optimized reaction conditions in hand, we turned our
attention to the investigation of the substrate scope (Table 2). Cyclic
g
ꢀ
MS 4 A (30 mg) was added.
b-hydroxy-a-diazo esters 2bef bearing a variety of aryl groups
could be utilized to give the corresponding cycloheptanones 3bef
without affecting the enantioselectivity (entries 2e6). In addition,
other functional groups, such as alkyl and siloxy groups were also
tolerated (entries 7 and 8). The absolute configuration of the
cilitate the isolation and the determination of the enantiose-
lectivity, the initial rearranged product was converted to
cycloheptanone 3a via the Krapcho decarboxylation.11 This pre-
liminary study revealed a remarkable difference in the reactivity
depending on the 3,30-substituents of the catalyst. Namely, the use
of the sterically encumbered (R)-1a bearing the 4-tert-butyl-2,6-
dimethylphenyl group led to the full consumption of cis-2a after
6 h at room temperature (entry 1). On the other hand, the reaction
catalyzed by (R)-1b bearing a 3,5-diphenylphenyl group led to the
instantaneous consumption of the substrate (entry 2). The elec-
tronic property of the aryl group also affected the reactivity, and the
apparent deceleration was observed with the electron-rich catalyst
(R)-1c (entry 3). Although axially chiral dicarboxylic acids actually
promoted the desired reaction, the enantioselectivity was low
irrespective of the catalyst structure. The modest yield is due to the
Table 2
Asymmetric semipinacol rearrangement of cyclic b-hydroxy-a
-diazo estersa
Entry
R
% Yieldb
% eec
1
2
3
4
5
6
7
8
Ph
2a
2b
2c
2d
2e
2f
60
68
65
57
72
60
73
68
3a
3b
3c
3d
3e
3f
80
79
80
78
81
77
82
73 (S)
4-tolyl
3-Tolyl
4-MeOC6H4
4-ClC6H4
2-Naphthyl
t-Bu
2g
2h
3g
3h
TBSO
a
Reactions were performed with (R)-1e (0.05 mmol), cis-2 (0.10 mmol), and H2O
(0.10 mmol) in toluene (1.0 mL).
b
Isolated yield.
Determined by chiral HPLC or GC analysis.
Fig. 3. Ortep representation of cis-2a with ellipsoids shown at 50% probability level.
Hydrogen atoms are omitted for clarity.
c

7632
T. Hashimoto et al. / Tetrahedron 68 (2012) 7630e7635
product was determined by comparison of the optical rotation of 3h
with the literature.13
The reaction could be extended to cyclic
b-hydroxy-a-diazo
ester 4 having two methyl groups at the 3- and 5-positions in a cis
fashion to give 3,5-cis-dimethylcycloheptanone 5 with modest
enantioselectivity (Scheme 2).
cis-2a
Scheme 4. Diastereoselective alkylation of the ring-expanded product.
3. Conclusions
In conclusion, we succeeded in developing axially chiral di-
carboxylic acid catalyzed asymmetric semipinacol rearrangement
of symmetrically substituted cyclic b-hydroxy-a-diazo esters. This
Scheme 2. Use of cyclic b-hydroxy-a-diazo ester with two methyl groups.
reaction provided an organocatalytic access to chiral heptanones
with modest to good enantioselectivities.
Furthermore, we implemented the reaction by using trans-2
placing the 4-substituent and the hydroxyl group in a trans-fashion
(Scheme 3). This study revealed a unique discrepancy between
trans-2a having a phenyl group and trans-2h having an OTBS group.
Whereas the former was found to be completely inert under the
reaction conditions, the latter gave the desired product (ent-3h)
with 77% ee, having the opposite optical rotation with that of the
reaction using the corresponding cis-2h.
4. Experimental section
4.1. General
Infrared (IR) spectra were recorded on a Shimadzu IRPrestige-21
spectrometer. 1H NMR spectra were measured on a JEOL JNM-
FX400 (400 MHz) spectrometer. Data were reported as follows:
chemical shifts in parts per million from tetramethylsilane as an
internal standard in CDCl3 or CD2HOD (d¼3.30) in CD3OD, in-
tegration, multiplicity (s¼singlet, d¼doublet, t¼triplet, q¼quartet,
dd¼double-doublet, m¼multiplet), coupling constants (hertz). 13C
NMR spectra were measured on a JEOL JNM-FX400 (100 MHz)
spectrometer with complete proton decoupling. Chemical shifts
were reported in ppm from the residual solvent as an internal
standard. High performance liquid chromatography (HPLC) was
performed on Shimadzu 10A instruments at 210 nm or 254 nm
using 4.6 mmꢂ25 cm Daicel Chiralpak AD-H column. Analytical
gas-liquid phase chromatography (GLC) was performed on Shi-
madzu GC-14B instruments equipped with a flame ionization de-
tector using a Chirasil-DEX CB (25 mꢂ0.25 mm). High-resolution
mass spectra (HRMS) were performed on Bruker microTOF. Opti-
cal rotations were measured on a JASCO DIP-1000 digital polar-
imeter. For thin layer chromatography (TLC) analysis throughout
this work, Merck precoated TLC plates (silica gel 60 GF254, 0.25 mm)
were used. The products were purified by flash column chroma-
tography silica gel 60 (Merck, 230e400 mesh) or Merck precoated
preparative thin layer chromatography (PTLC) plate (silica gel 60
GF254, 0.5 mm). In experiments requiring dry solvent, tetrahydro-
furan, and diethyl ether were purchased from Kanto Chemical Co.
Inc. as ‘Dehydrated’. Dichloromethane and toluene were stored
Scheme 3. Use of trans-cyclic b-hydroxy-a-diazo esters.
DFT calculations of the relative energy differences (B3LYP/6-
31G(d) for trans-2a, and B3LYP/6-31G(d,p) for trans-2h) indicated
that trans-2a with the axial diazo ester moiety and trans-2h with
the equatorial diazo ester moiety are the favored conformations
(Fig. 4). This observation, in line with the X-ray analysis of the re-
active substrate cis-2a and cis-2h,10 underlines the importance of
the chair conformer with the axial hydroxyl group and the equa-
torial diazo ester to trigger the rearrangement.
Finally, we decided to exploit the b-keto ester generated in the
initial rearrangement (Scheme 4). After treatment of cis-2a with
(R)-1e, the reaction was directly subjected to phase-transfer cata-
lyzed benzylation in one pot to give cyclic b-keto ester 6 having an
ꢀ
over 4 A molecular sieves. Other simple chemicals were purchased
and used as such.
all-carbon quaternary center. The reaction proceeded smoothly at
room temperature to give the desired compound in 55% yield with
high diastereoselectivity.3b
4.2. Representative procedure for the preparation of starting
materials
To a stirred solution of 4-phenylcyclohexanone (1.5 mmol,
261 mg) and ethyl diazoacetate (1.8 mmol, 205 mg) in THF (2.0 mL)
was added lithium diisopropylamide [prepared by the addition of
butyllithium in hexane (1.95 mmol, 1.25 mL) to a solution of dii-
sopropylamine (1.95 mmol, 0.27 mL) in Et2O (2.0 mL) at 0 ꢁC]
dropwise at ꢀ78 ꢁC. After stirring for 3 h at ꢀ78 ꢁC, saturated
aqueous NH4Cl was added to the solution. The organic layer was
extracted with ethyl acetate, dried over Na2SO4, and concentrated.
The residue was purified by column chromatography on silica gel
with hexane/ethyl acetate¼20:1 to give cis-2a [40% (173 mg)] and
trans-2a [21% (90 mg)].
Fig. 4. Computed relative energy differences of trans-2.

T. Hashimoto et al. / Tetrahedron 68 (2012) 7630e7635
7633
4.2.1. Ethyl cis-2-diazo-2-(1-hydroxy-4-phenylcyclohexyl)acetate (cis-
125.2, 124.7, 68.8, 60.9, 43.7, 36.5, 28.8, 14.4; IR (neat) 3468, 2928,
2856, 2087, 1445, 1369, 1298, 1098, 1042 cmꢀ1; HRMS (ESI) exact
mass calcd for C20H22N2O3: m/z 361.1523 ([MþNa]þ), found: m/z
361.1505 ([MþNa]þ).
2a). Yellow solid; mp 65e67 ꢁC; 1H NMR (400 MHz, CDCl3)
d
7.32e7.17 (5H, m), 4.26 (2H, q, J¼7.1 Hz), 3.58 (1H, s), 2.54 (1H, m),
2.22 (2H, m), 2.03 (2H, m), 1.77 (2H, m), 1.66 (2H, m), 1.30 (3H, t,
J¼7.1 Hz); 13C NMR (100 MHz, CDCl3)
d 167.2, 146.6, 128.3, 126.8,
126.0, 68.7, 60.8, 43.5, 36.3, 32.5, 28.8. 14.4; IR (neat) 3473, 2930,
2087, 1670, 1448, 1369, 1301, 1099, 746, 700 cmꢀ1; HRMS (ESI) exact
mass calcd for C16H20N2O3: m/z 311.1367 ([MþNa]þ), found: m/z
311.1368 ([MþNa]þ).
4.2.8. Ethyl cis-2-diazo-2-(4-tert-butyl-1-hydroxycyclohexyl)acetate
(cis-2g). Yellow solid; mp 40e42 ꢁC; 1H NMR (400 MHz, CDCl3)
d
4.24 (2H, q, J¼7.2 Hz), 3.44 (1H, s), 2.13 (2H, m), 1.63 (2H, m),
1.56e1.43 (4H, m), 1.28 (3H, t, J¼7.1 Hz), 1.01 (1H, m), 0.87 (9H, s);
13C NMR (100 MHz, CDCl3)
167.4, 69.0, 60.7, 47.5, 36.7, 32.4, 27.5,
d
4.2.2. Ethyl trans-2-diazo-2-(1-hydroxy-4-phenylcyclohexyl)acetate
22.2, 14.4; IR (neat) 3471, 2953, 2087, 1674, 1367, 1298, 1099,
1035 cmꢀ1; HRMS (ESI) exact mass calcd for C14H24N2O3: m/z
291.1679 ([MþNa]þ), found: m/z 291.1679 ([MþNa]þ).
(trans-2a). Yellow oil; 1H NMR (400 MHz, CDCl3)
d 7.32e7.18 (5H,
m), 4.26 (2H, q, J¼7.1 Hz), 3.56 (1H, s), 2.62 (1H, m), 2.38 (2H, m),
1.93 (2H, m), 1.79 (2H, m), 1.47 (2H, m), 1.31 (3H, t, J¼7.1 Hz); 13C
NMR (100 MHz, CDCl3)
d
166.9, 145.6, 128.3, 126.7, 126.2, 71.6, 60.8,
4.2.9. Ethyl cis-2-diazo-2-(4-(tert-butyldimethylsilyloxy)-1-
42.8, 36.7, 30.8, 14.3; IR (neat) 3452, 2931, 2088, 1682, 1294,
1085 cmꢀ1; HRMS (ESI) exact mass calcd for C16H20N2O3: m/z
311.1367 ([MþNa]þ), found: m/z 311.1360 ([MþNa]þ).
hydroxycyclohexyl)acetate (cis-2h). Yellow oil; 1H NMR (400 MHz,
CDCl3)
m), 1.88 (2H, m), 1.78 (2H, m), 1.49 (2H, m), 1.29 (3H, t, J¼7.1 Hz),
0.88 (9H, s), 0.04 (6H, s); 13C NMR (100 MHz, CDCl3)
167.3, 69.8,
d
4.24 (2H, q, J¼7.2 Hz), 3.92 (1H, m), 3.51 (1H, m), 2.00 (2H,
d
4.2.3. Ethyl cis-2-diazo-2-(1-hydroxy-4-(4-methylphenyl)cyclohexyl)
66.5, 60.7, 31.2, 29.6, 25.8, 18.0, 14.4, ꢀ4.9; IR (neat) 3487, 2930,
2087, 1676, 1369, 1300, 1254, 1032 cmꢀ1; HRMS (ESI) exact mass
calcd for C16H30N2O4Si: m/z 365.1867 ([MþNa]þ), found: m/z
365.1868 ([MþNa]þ).
acetate (cis-2b). Yellow solid; mp 68e70 ꢁC; 1H NMR (400 MHz,
CDCl3)
d
7.17e7.09 (4H, m), 4.26 (2H, q, J¼7.2 Hz), 3.57 (1H, s), 2.50
(1H, m), 2.32 (3H, s), 2.21 (2H, m), 1.99 (2H, m), 1.74 (2H, m), 1.66
(2H, m), 1.30 (3H, t, J¼7.1 Hz); 13C NMR (100 MHz, CDCl3)
d 167.3,
143.6, 135.5, 129.0, 126.7, 68.7, 60.8, 43.1, 36.4, 28.9, 20.9. 14.4; IR
(neat) 3483, 2926, 2086, 1672, 1300, 1111, 1041 cmꢀ1; HRMS (ESI)
exact mass calcd for C17H22N2O3: m/z 325.1523 ([MþNa]þ), found:
m/z 325.1512 ([MþNa]þ).
4.2.10. Ethyl trans-2-diazo-2-(4-(tert-butyldimethylsilyloxy)-1-
hydroxycyclohexyl)acetate (trans-2h). Yellow oil; 1H NMR
(400 MHz, CDCl3)
2.08 (2H, m), 1.82e1.60 (6H, m), 1.28 (3H, t, J¼7.1 Hz), 0.89 (9H, s),
0.05 (6H, s); 13C NMR (100 MHz, CDCl3)
167.1, 69.2, 69.0, 60.8,
d
4.24 (2H, q, J¼7.2 Hz), 3.68 (1H, s), 3.36 (1H, s),
d
4.2.4. Ethyl cis-2-diazo-2-(1-hydroxy-4-(3-methylphenyl)cyclohexyl)
33.6, 30.8, 25.8, 18.1, 14.4, ꢀ4.7; IR (neat) 3477, 2931, 2089, 1678,
1369, 1300, 1253, 1094 cmꢀ1; HRMS (ESI) exact mass calcd for
C16H30N2O4Si: m/z 365.1867 ([MþNa]þ), found: m/z 365.1873
([MþNa]þ).
acetate (cis-2c). Yellow solid; mp 62e64 ꢁC; 1H NMR (400 MHz,
CDCl3)
d
7.19 (1H, t, J¼7.5 Hz), 7.08e7.00 (3H, m), 4.26 (2H, q,
J¼7.1 Hz), 3.60 (1H, s), 2.51 (1H, m), 2.34 (3H, s), 2.21 (2H, m), 2.02
(2H, m), 1.75 (2H, m), 1.65 (2H, m), 1.31 (3H, q, J¼7.1 Hz); 13C NMR
(100 MHz, CDCl3)
d
167.4, 146.6, 137.9, 128.3, 127.6, 126.9, 123.9,
4.2.11. Compound 4. Yellow solid; mp 55e57 ꢁC; 1H NMR
68.8, 60.8, 43.6, 36.5, 28.8, 21.4, 14.4; IR (neat) 3480, 2926, 2089,
1676, 1301, 1101, 1041 cmꢀ1; HRMS (ESI) exact mass calcd for
C17H22N2O3: m/z 325.1523 ([MþNa]þ), found: m/z 325.1515
([MþNa]þ).
(400 MHz, CDCl3)
d
4.24 (2H, q, J¼7.2 Hz), 3.54 (1H, s), 2.04 (2H, m),
1.94 (2H, m), 1.70 (1H, m), 1.29 (3H, t, J¼7.1 Hz), 1.03 (2H, t,
J¼12.6 Hz), 0.90 (6H, d, J¼6.8 Hz), 0.56 (1H, q, J¼12.2 Hz); 13C NMR
(100 MHz, CDCl3)
d 167.4, 70.4, 60.7, 44.2, 43.2, 27.4, 22.0, 14.4; IR
(neat) 3480, 2951, 2086, 1674, 1303, 1128, 1093 cmꢀ1; HRMS (ESI)
exact mass calcd for C12H20N2O3: m/z 263.1366 ([MþNa]þ), found:
m/z 263.1371 ([MþNa]þ).
4.2.5. Ethyl cis-2-diazo-2-(1-hydroxy-4-(4-methoxyphenyl)cyclohexyl)
acetate (cis-2d). Yellow solid; mp 58e60 ꢁC; 1H NMR (400 MHz,
CDCl3)
d
7.17 (2H, m), 6.84 (2H, m), 4.26 (2H, q, J¼7.1 Hz), 3.78 (3H, s),
3.58 (1H, s), 2.49 (1H, m), 2.20 (2H, m), 1.97 (2H, m), 1.73 (2H, m), 1.65
(2H, m), 1.30 (3H, t, J¼7.1 Hz); 13C NMR (100 MHz, CDCl3)
d 167.4,
157.9,138.8,127.7,113.8, 68.7, 60.8, 55.2, 42.7, 36.5, 29.0,14.4; IR (neat)
3483, 2935, 2086, 1676, 1512, 1301, 1247, 1111, 1039 cmꢀ1; HRMS (ESI)
exact mass calcd for C17H22N2O4: m/z 341.1472 ([MþNa]þ), found: m/
z 341.1476 ([MþNa]þ).
4.3. Preparation of catalyst (R)-1e
4.3.1. Bis(2-(trimethylsilyl)ethyl) (R)-3,30-bis(dihydroxyborane)-1,10-
binaphthyl-2,20-dicarboxylate. To
a 0.25 M THF solution of
Mg(TMP)2 (25 mmol, 100 mL) prepared according to the litera-
ture14 was added bis(2-(trimethylsilyl)ethyl) (R)-1,10-binaphthyl-
2,20-dicarboxylate (5.0 mmol, 2.71 g)8a,b in THF (10 mL) dropwise at
ꢀ78 ꢁC. The mixture was then allowed to warm to room temper-
ature and stirred for 2 h. After being cooled to ꢀ78 ꢁC, B(OMe)3
(30 mmol, 3.34 mL) was added and the reaction was stirred for 12 h
at room temperature. This mixture was then poured into cold 1 M
HCl (30 mL), and extracted with EtOAc. The organic layer was
washed with water and brine, dried over Na2SO4, and concentrated
under reduced pressure. The residue was washed with hexane to
give the title compound as a pale yellow solid [65% (2.04 g)]. Mp
4.2.6. Ethyl cis-2-diazo-2-(4-(4-chlorophenyl)-1-hydroxycyclohexyl)
acetate (cis-2e). Yellow solid; mp 68e70 ꢁC; 1H NMR (400 MHz,
CDCl3)
d
7.26 (2H, m), 7.17 (2H, m), 4.26 (2H, q, J¼7.1 Hz), 3.60 (1H,
s), 2.52 (1H, m), 2.21 (2H, m),1.97 (2H, m),1.74 (2H, m),1.65 (2H, m),
1.30 (3H, q, J¼7.1 Hz); 13C NMR (100 MHz, CDCl3) 167.3, 145.0, 131.7,
128.4, 128.2, 68.6, 60.9, 43.0, 36.3, 28.8, 14.4; IR (neat) 3475, 2931,
2088, 1674, 1301, 1093 cmꢀ1; HRMS (ESI) exact mass calcd for
C16H19ClN2O3: m/z 345.0976 ([MþNa]þ), found: m/z 345.0974
([MþNa]þ).
4.2.7. Ethyl cis-2-diazo-2-(1-hydroxy-4-(2-naphthyl)cyclohexyl)ace-
decomp. >250 ꢁC; 1H NMR (400 MHz, CD3OD)
d 7.93 (2H, s), 7.90
tate (cis-2f). Yellow solid; mp 110e112 ꢁC; 1H NMR (400 MHz,
(2H, d, J¼8.2 Hz), 7.45 (2H, m), 7.17 (2H, m), 6.96 (2H, d, J¼8.7 Hz),
CDCl3) d 7.81e7.77 (3H, m), 7.67 (1H, s), 7.46e7.39 (3H, m), 4.27 (2H,
3.68 (4H, m), 0.07 (4H, m), ꢀ0.27 (18H, s); 13C NMR (100 MHz,
q, J¼7.1 Hz), 3.63 (1H, s), 2.71 (1H, m), 2.26 (2H, m), 2.12 (2H, m),
CD3OD) d170.7, 140.7, 136.1, 134.5, 131.9, 131.3, 129.1, 129.1, 128.2,
1.85 (2H, m), 1.72 (2H, m), 1.31 (3H, t, J¼7.1 Hz); 13C NMR (100 MHz,
128.0, 64.6, 17.6, ꢀ1.8; IR (neat) 3399, 1699, 1419, 1386, 1276, 1134,
CDCl3)
d 167.4, 144.1, 133.6, 132.2, 127.9, 127.6, 127.5, 126.0, 125.9,
1058 cmꢀ1; HRMS (ESI) exact mass calcd for C32H40B2O8Si2: m/z

7634
T. Hashimoto et al. / Tetrahedron 68 (2012) 7630e7635
681.2666 ([Mꢀ2H2Oþ2MeOHþNa]þ), found: m/z 681.2661
mass calcd for C13H16O: m/z 211.1093 ([MþNa]þ), found: m/z
211.1087 ([MþNa]þ); HPLC analysis: Daicel Chiralpak AD-H, hex-
ane/i-PrOH¼50:1, flow rate¼0.5 mL/min, retention time 19.7 min
([Mꢀ2H2Oþ2MeOHþNa]þ); ½a D24
ꢃ
21.7 (c 1.0, MeOH).
4.3.2. Bis(2-(trimethylsilyl)ethyl) (R)-3,30-bis(3,5-dinitrophenyl)-1,10-
binaphthyl-2,20-dicarboxylate. To a Schlenk tube equipped with
a rubber septum and a magnetic stir bar were added Pd(OAc)2
(0.050 mmol, 10.2 mg), triphenylphosphine (0.20 mmol, 52.5 mg),
3,5-dinitrobromobenzene (1.5 mmol, 308 mg), NaHCO3 (1.5 mmol,
126 mg), and bis(2-(trimethylsilyl)ethyl) (R)-3,30-bis(dihydrox-
yborane)-1,10-binaphthyl-2,20-dicarboxylate (0.50 mmol, 315 mg).
The Schlenk tube was then evacuated and backfilled with argon.
After adding THF (2.0 mL) and water (1.0 mL) to the Schlenk tube,
the rubber septum was replaced by a glass stopper and the reaction
was stirred for 12 h at 60 ꢁC. The mixture was then cooled to room
temperature and poured into saturated aqueous NH4Cl. The organic
layer was extracted with EtOAc, dried over Na2SO4, and concen-
trated. The residue was purified by column chromatography on
silica gel with hexane/EtOAc¼20:1 to give the title compound as
(minor) and 29.8 min (major); ½a D32
ꢃ
104.2 (c 0.84, CHCl3 (80% ee)).
4.4.2. (S)-4-(4-Methylphenyl)cycloheptanone (3b). Colorless oil; 1H
NMR (400 MHz, CDCl3) 7.13e7.04 (4H, m), 2.68 (2H, m), 2.61e2.54
(3H, m), 2.31 (3H, s), 2.11 (1H, m), 2.00 (2H, m), 1.86 (1H, m), 1.76
(1H, m), 1.62 (1H, m); 13C NMR (100 MHz, CDCl3)
214.7, 144.6,
d
d
135.7, 129.2, 126.3, 48.3, 43.8, 42.9, 38.4, 32.0, 23.8, 20.9; IR (neat)
2924, 1699, 1514 cmꢀ1; HRMS (ESI) exact mass calcd for C14H18O:
m/z 225.1250 ([MþNa]þ), found: m/z 225.1249 ([MþNa]þ); HPLC
analysis: Daicel Chiralpak AD-H, hexane/i-PrOH¼50:1, flow
rate¼0.5 mL/min, retention time 25.3 min (minor) and 29.1 min
(major); ½a 3D2
ꢃ
98.3 (c 0.82, CHCl3 (79% ee)).
4.4.3. (S)-4-(3-Methylphenyl)cycloheptanone (3c). Colorless oil; 1H
NMR (400 MHz, CDCl3)
d
7.19 (1H, t, J¼7.5 Hz), 7.03e6.97 (3H, m),
a colorless oil [62% (271 mg)]. 1H NMR (400 MHz, CDCl3)
d
9.07 (2H,
2.73e2.56 (5H, m), 2.34 (3H, s), 2.12 (1H, m), 2.06e1.98 (2H, m),1.87
t, J¼1.9 Hz), 8.70 (4H, d, J¼1.9 Hz), 8.08 (2H, s), 8.04 (2H, d,
J¼8.2 Hz), 7.67 (2H, m), 7.50 (2H, m), 7.35 (2H, d, J¼8.7 Hz), 3.65
(4H, m), 0.09 (4H, m), ꢀ0.18 (18H, s); 13C NMR (100 MHz, CDCl3)
(1H, m), 1.75 (1H, m), 1.63 (1H, m); 13C NMR (100 MHz, CDCl3)
d
214.7, 147.6, 138.1, 128.4, 127.3, 127.0, 123.5, 48.7, 43.8, 42.9, 38.4,
31.9, 23.9, 21.4; IR (neat) 2926, 1699, 1452 cmꢀ1; HRMS (ESI) exact
mass calcd for C14H18O: m/z 225.1250 ([MþNa]þ), found: m/z
225.1241 ([MþNa]þ); HPLC analysis: Daicel Chiralpak AD-H, hex-
ane/i-PrOH¼50:1, flow rate¼0.5 mL/min, retention time 16.5 min
d
167.1, 148.4, 144.5, 136.2, 133.1, 132.9, 132.8, 131.0, 130.3, 128.7,
128.6, 128.6, 128.3, 127.5, 117.6, 63.7, 16.6, ꢀ1.9; IR (neat) 1720, 1541,
1342, 1274, 1136 cmꢀ1
; HRMS (ESI) exact mass calcd for
C44H42N4O12Si2: m/z 897.2230 ([MþNa]þ), found: m/z 897.2216
(minor) and 19.5 min (major); ½a D32
ꢃ
78.2 (c 0.64, CHCl3 (80% ee)).
([MþNa]þ); ½a 2D4
þ5.0 (c 1.0, CHCl3).
ꢃ
4.4.4. (S)-4-(4-Methoxyphenyl)cycloheptanone (3d). Colorless oil;
1H NMR (400 MHz, CDCl3)
7.10 (2H, m), 6.84 (2H, m), 3.79 (3H, s),
2.73e2.52 (5H, m), 2.08 (1H, m), 2.05e1.96 (2H, m), 1.88e1.70 (2H,
m), 1.60 (1H, m); 13C NMR (100 MHz, CDCl3)
214.7, 157.9, 139.8,
4.3.3. (R)-3,30-Bis(3,5-dinitrophenyl)-1,10-binaphthyl-2,20-dicarboxylic
acid (R)-(1e). To a stirred solution of the ester (0.31 mmol, 271 mg) in
THF (1.0 mL) was added a 1 M solution of tetrabutylammonium
fluoride in THF (3.1 mmol, 3.1 mL). After stirring for 8 h at room
temperature, the mixture was treated with 1 M HCl. The organic layer
was extracted with EtOAc, dried over Na2SO4, and concentrated. The
residue was purified by column chromatography on silica gel with
hexane/EtOAc/AcOH¼1:1:0.005 to give (R)-1e as a white solid [82%
d
d
127.3, 113.9, 55.2, 47.9, 43.8, 42.9, 38.5, 32.1, 23.8; IR (neat) 2924,
1697, 1510, 1456, 1244, 1178, 1033 cmꢀ1; HRMS (ESI) exact mass
calcd for C14H18O2: m/z 241.1199 ([MþNa]þ), found: m/z 241.1199
([MþNa]þ); HPLC analysis: Daicel Chiralpak AD-H, hexane/i-
PrOH¼50:1, flow rate¼0.5 mL/min, retention time 35.0 min (mi-
(222 mg)]. Mp decomp. >200 ꢁC; 1H NMR (400 MHz, CD3OD)
d
8.94
nor) and 42.2 min (major); ½a D32
ꢃ
92.7 (c 0.78, CHCl3 (78% ee)).
(2H, t, J¼1.9 Hz), 8.73 (4H, d, J¼1.8 Hz), 8.18 (2H, s), 8.03 (2H, d,
J¼8.2 Hz), 7.55 (2H, m), 7.35 (2H, m), 7.17 (2H, d, J¼8.7 Hz); 13C NMR
4.4.5. (S)-4-(4-Chlorophenyl)cycloheptanone (3e). Colorless oil; 1H
NMR (400 MHz, CDCl3) 7.25 (2H, m), 7.10 (2H, m), 2.71e2.51 (5H,
m), 2.11e1.94 (3H, m), 1.87e1.69 (2H, m), 1.58 (1H, m); 13C NMR
(100 MHz, CD3OD)
d
171.1, 149.8, 146.0, 136.9, 134.7, 134.4, 134.0, 133.0,
d
131.7, 129.9, 129.7, 129.3, 129.2, 128.3, 118.4; IR (neat) 2922, 1737, 1537,
1342 cmꢀ1; HRMS (ESI) exact mass calcd for C34H18N4O12: m/z
(100 MHz, CDCl3) d 214.3, 145.9, 131.8, 128.6, 127.8, 48.1, 43.7, 42.7,
673.0837 ([MþNa]þ), found: m/z 673.0823 ([MþNa]þ); ½a 2D5
ꢃ
þ8.9 (c
38.3, 31.8, 23.7; IR (neat) 2924, 1697, 1490, 1091, 1012 cmꢀ1; HRMS
(ESI) exact mass calcd for C13H15ClO: m/z 245.0704 ([MþNa]þ),
found: m/z 245.0709 ([MþNa]þ); HPLC analysis: Daicel Chiralpak
AD-H, hexane/i-PrOH¼50:1 flow rate¼0.5 mL/min, retention time
0.5, CH3OH).
4.4. General procedure for the asymmetric semipinacol
rearrangement of cyclic
b
-hydroxy-
a
-diazo esters
28.5 (minor) min and 33.2 min (major); ½a D32
ꢃ
92.1 (c 0.79, CHCl3
(81% ee)).
To a solution of (R)-1e (0.005 mmol, 3.3 mg) in toluene (1.0 mL)
and H2O (0.10 mmol, 1.8
m
L) was added cis-2 (0.10 mmol) at ꢀ40 ꢁC,
4.4.6. (S)-4-(2-Naphthyl)cycloheptanone (3f). Colorless oil; 1H NMR
(400 MHz, CDCl3) 7.81e7.77 (3H, m), 7.61 (1H, s), 7.48e7.40 (2H,
and the reaction was stirred for 48 h at ꢀ40 ꢁC. The solvent was
d
then removed under reduced pressure. The residue was purified by
m), 7.33 (1H, dd, J¼8.5, 1.7 Hz), 2.86 (1H, m), 2.75 (1H, m),
PTLC with hexane/EtOAc¼4:1 to give the corresponding cyclic
b-
2.66e2.60 (3H, m), 2.20 (1H, m), 2.15e1.93 (3H, m), 1.88e1.69 (2H,
keto ester. To a solution of thus-obtained cyclic -keto ester in
b
m); 13C NMR (100 MHz, CDCl3)
d 214.6, 144.9, 133.6, 132.2, 128.1,
DMSO (1.0 mL) was added lithium chloride (0.10 mmol, 4.3 mg) at
room temperature. The mixture was stirred at 160 ꢁC for 3 h. The
resulting solution was poured into brine and extracted with EtOAc.
The combined organic layers were dried over Na2SO4 and removed
under reduced pressure. The residue was purified by PTLC with
hexane/EtOAc¼4:1 to give 3.
127.6, 126.0, 125.5, 125.4, 124.4, 48.8, 43.8, 42.9, 38.3, 31.8, 23.9; IR
(neat) 2922,1697,1452,1342 cmꢀ1; HRMS (ESI) exact mass calcd for
C17H18O: m/z 261.1250 ([MþNa]þ), found: m/z 261.1251 ([MþNa]þ);
HPLC analysis: Daicel Chiralpak AD-H, hexane/i-PrOH¼100:1, flow
rate¼0.5 mL/min, retention time 21.7 min (minor) and 25.5 min
(major); ½a 3D2
ꢃ
80.2 (c 0.95, CHCl3 (77% ee)).
4.4.1. (S)-4-Phenylcycloheptanone (3a).3e Colorless oil; 1H NMR
4.4.7. (S)-4-(tert-Butyl)cycloheptanone (3g). Colorless oil; 1H NMR
(400 MHz, CDCl3) 2.49e2.34 (4H, m), 2.02 (1H, m), 1.94e1.88 (2H,
m), 1.50 (1H, m), 1.25 (1H, m), 1.10e0.97 (2H, m), 0.81 (9H, s); 13C
NMR (100 MHz, CDCl3) 215.6, 52.0, 43.6, 43.1, 33.6, 31.0, 27.5, 25.6,
24.2; IR (neat) 2951, 1703, 1367 cmꢀ1; HRMS (ESI) exact mass calcd
(400 MHz CDCl3)
2.03 (2H, m), 1.89 (1H, m), 1.79 (1H, m), 1.65 (1H, m); 13C NMR
(100 MHz, CDCl3) 214.7, 147.6, 128.5, 126.5, 126.2, 48.8, 43.8, 42.9,
38.4, 31.8, 23.8; IR (neat) 2924, 1699, 1452 cmꢀ1; HRMS (ESI) exact
d
7.32e7.17 (5H, m), 2.65 (5H, m), 2.11 (1H, m),
d
d
d

T. Hashimoto et al. / Tetrahedron 68 (2012) 7630e7635
7635
for C11H20O: m/z 191.1406 ([MþNa]þ), found: m/z 191.1400
([MþNa]þ); GLC analysis: Chirasil-DEX CB (25 mꢂ0.25 mm) column
(100 ꢁC isotherm, N2: 80 kPa, He: 80 kPa), retention time 42.2 min
saturated aqueous NH4Cl. The organic layer was extracted with
EtOAc, dried over Na2SO4 and concentrated. The residue was pu-
rified by PTLC with hexane/EtOAc¼4:1 to give 6 as a colorless oil
(minor) and 43.0 min (major); ½a D32
ꢃ
80.2 (c 0.95 CHCl3 (82% ee)).
[55% (19.3 mg)]. 1H NMR (400 MHz, CDCl3)
d 7.29e7.10 (10H, m),
4.23 (2H, m), 3.23 (2H, s), 2.64 (1H, m), 2.53 (1H, m), 2.33 (1H, m),
4.4.8. (S)-4-(tert-Butyldimethylsilyloxy)-cycloheptanone (3h).13
Colorless oil; 1H NMR (400 MHz, CDCl3)
4.02 (1H, m), 2.84 (1H,
2.17 (1H, m), 1.98e1.17 (5H, m), 1.29 (3H, t, J¼7.1 Hz); 13C NMR
d
(100 MHz, CDCl3) d 210.3, 172.4, 147.1, 136.1, 130.5, 128.5, 128.2,
m), 2.50 (1H, m), 2.41 (1H, m), 2.28 (1H, m), 1.98 (1H, m),
126.9, 126.5, 126.3, 64.0, 61.2, 47.7, 43.0, 43.0, 33.3, 33.3, 31.2, 14.1;
IR (neat) 2932, 1730, 1701, 1450, 1228, 1201 cmꢀ1; HRMS (ESI) exact
mass calcd for C23H26O3: m/z 373.1774 ([MþNa]þ), found: m/z
373.1789 ([MþNa]þ); HPLC analysis: Daicel Chiralpak AD-H, hex-
ane/i-PrOH¼99:1, flow rate¼0.5 mL/min, retention time 36.6 min
1.88e1.75 (3H, m), 1.68 (1H, m), 1.55 (1H, m), 0.91 (9H, s), 0.08
(6H, s); 13C NMR (100 MHz, CDCl3)
d 214.8, 70.0, 43.7, 38.4, 37.1,
32.1, 25.7, 18.0, 17.9, ꢀ4.9, ꢀ4.9; IR (neat) 2929, 1703, 1467, 1255,
1080 cmꢀ1; HRMS (ESI) exact mass calcd for C13H26O2Si: m/z
265.1594 ([MþNa]þ), found: m/z 265.1588 ([MþNa]þ); ½a 2D4
ꢃ
ꢀ4.70
(minor) and 44.5 min (major); ½a D32
ꢃ
23.1 (c 1.02, CHCl3 (79% ee)).
(c 0.41, CHCl3 (73% ee)).
Acknowledgements
4.4.8.1. Determination of the enantioselectivity of 3h. To a solu-
tion of 3h (0.067 mmol, 16.2 mg) in MeOH (1.0 mL) was added
NaBH4 (0.79 mmol, 30 mg) at 0 ꢁC. After stirring for 1 h at room
temperature, the mixture was quenched with saturated aqueous
NaHCO3 and the organic layer was extracted with Et2O. The com-
bined organic layers were dried over Na2SO4 and concentrated. The
residue was purified by column chromatography on silica gel with
hexane/Et2O¼5:1 to give the cycloheptanol as a diastereo mixture.
To a solution of thus-obtained cycloheptanol in THF (1.0 mL) was
This work was partially supported by a Grant-in-Aid for Scien-
tific Research from the MEXT, Japan. T.H. thanks a Grant-in-Aid for
Challenging Exploratory Research.
Supplementary data
Supplementary data related to this article can be found online at
http://dx.doi.org/10.1016/j.tet.2012.06.033.
added pyridine (2.0 mmol, 16
aminopyridine (0.033 mmol, 4.0 mg). The mixture was added
BzCl (0.10 mmol, 12
L) at 0 ꢁC and stirred for 2 h at room tem-
mL) and N,N-dimethyl-4-
References and notes
m
1. Tiffeneau, M.; Weill, P.; Tchoubar, B. Compt. Rend. 1937, 205, 54e56.
2. For reviews, see: (a) Zhang, Y.; Wang, J. Chem. Commun. 2009, 5350e5361; (b)
Johnston, J. N.; Muchalski, H.; Troyer, T. L. Angew. Chem., Int. Ed. 2010, 49,
2290e2298.
perature. The resulting solution was quenched with saturated
aqueous NH4Cl and the organic layer was extracted with EtOAc. The
combined organic layers were dried over Na2SO4 and concentrated.
The residue was purified by PTLC with hexane/CH2Cl2¼1:1 to iso-
late the upper fraction as a diastereo pure 4-((tert-butyldime-
thylsilyl)oxy)-cycloheptyl benzoate (relative configuration not
assigned) [47% (11.0 mg)]. Colorless oil; 1H NMR (400 MHz, CDCl3)
3. For our works on this subject, see: (a) Hashimoto, T.; Naganawa, Y.; Maruoka, K. J.
Am. Chem. Soc. 2008,130, 2434e2435; (b) Hashimoto, T.; Naganawa, Y.; Maruoka,
K. J. Am. Chem. Soc. 2009, 131, 6614e6617; (c) Hashimoto, T.; Miyamoto, H.; Na-
ganawa, Y.; Maruoka, K. J. Am. Chem. Soc. 2009,131,11280e11281; (d) Hashimoto,
T.; Naganawa, Y.; Maruoka, K. Chem. Commun. 2010, 6810e6812; (e) Hashimoto,
T.; Naganawa, Y.; Maruoka, K. J. Am. Chem. Soc. 2011, 133, 8834e8837.
4. For other recent works, see: (a) Moebius, D. C.; Kingsbury, J. S. J. Am. Chem. Soc.
2009, 131, 878e879; (b) Wommack, A. J.; Moebius, D. C.; Travis, A. L.; Kingsbury,
J. S. Org. Lett. 2009, 11, 3202e3205; (c) Rendina, V. L.; Moebius, D. C.; Kingsbury,
J. S. Org. Lett. 2011, 13, 2004e2007; (d) Li, W.; Wang, J.; Hu, X.; Shen, K.; Wang,
W.; Chu, Y.; Lin, L.; Liu, X.; Feng, X. J. Am. Chem. Soc. 2010, 132, 8532e8533.
d
8.04 (2H, d, J¼8.3 Hz), 7.54 (1H, t, J¼7.4 Hz), 7.43 (2H, t, J¼7.6 Hz),
5.17 (1H, m), 3.91 (1H, m), 2.11e2.00 (2H, m), 1.90e1.60 (7H, m),
1.36 (1H, m), 0.90 (9H, s), 0.053 (3H, s), 0.049 (3H, s); 13C NMR
(100 MHz, CDCl3)
d 165.9, 132.7, 131.0, 129.5, 128.2, 74.9, 71.5, 38.1,
33.9, 31.8, 27.4, 25.9, 18.5, 18.1, ꢀ4.8, ꢀ4.8; IR (neat) 2953, 2854,
1716, 1273, 1111, 1068 cmꢀ1; HRMS (ESI) exact mass calcd for
C20H32O3Si: m/z 371.2013 ([MþNa]þ), found: m/z 371.2016
([MþNa]þ); HPLC analysis: Daicel Chiralpak AD-H, hexane/i-
PrOH¼400:1 flow rate¼0.3 mL/min, retention time 18.4 min (mi-
€
ꢁ
5. (a) Schollkopf, U.; Banhidai, B.; Frasnelli, H.; Meyer, R.; Beckhaus, H. Liebigs Ann.
ꢁ
Chem. 1974, 1767e1783; (b) Hebrault, D.; Uguen, D.; De Cian, A.; Fischer, J.
Tetrahedron Lett. 1998, 39, 6703e6706.
6. (a) Pellicciari, R.; Fringuelli, R.; Ceccherelli, P.; Sisani, E. J. Chem. Soc., Chem.
Commun. 1979, 959e960; (b) Nagao, K.; Chiba, M.; Kim, S.-W. Synthesis 1983,
197e199; (c) Ye, T.; McKervey, M. A. Tetrahedron 1992, 48, 8007e8022.
7. (a) Pellicciari, R.; Natalini, B.; Sadeghpour, B. M.; Rosato, G. C.; Ursini, A. J. Chem.
Soc., Chem. Commun. 1993, 1798e1800; (b) Pellicciari, R.; Natalini, B.; Sa-
deghpour, B. M.; Marinozzi, M.; Snyder, J. P.; Williamson, B. L.; Kuethe, J. T.;
Padwa, A. J. Am. Chem. Soc. 1996, 118, 1e12; (c) Gioiello, A.; Venturoni, F.; Na-
talini, B.; Pellicciari, R. J. Org. Chem. 2009, 74, 3520e3523.
nor) and 19.3 min (major); ½a D32
ꢀ7.4 (c 0.75, CHCl3 (73% ee)).
ꢃ
4.4.9. (3R,5R)-cis-3,5-Dimethylcycloheptanone (5). Colorless oil; 1H
NMR (400 MHz, CDCl3) 2.53e2.44 (2H, m), 2.37 (2H, m), 1.88 (1H,
d
8. (a) Hashimoto, T.; Maruoka, K. J. Am. Chem. Soc. 2007, 129, 10054e10055; (b)
Hashimoto, T.; Maruoka, K. Synthesis 2008, 3703e3706; (c) Hashimoto, T.; Hirose,
M.; Maruoka, K. J. Am. Chem. Soc. 2008, 130, 7556e7557; (d) Hashimoto, T.;
Uchiyama, N.; Maruoka, K. J. Am. Chem. Soc. 2008, 130, 14380e14381; (e) Ha-
shimoto, T.; Kimura, H.; Maruoka, K. Tetrahedron: Asymmetry 2010, 21,
1187e1188; (f) Hashimoto, T.; Kimura, H.; Maruoka, K. Angew. Chem., Int. Ed. 2010,
49, 6844e6847; (g) Hashimoto, T.; Takagaki, T.; Kimura, H.; Maruoka, K. Chem.
dAsian J. 2011, 6, 1936e1938; (h) Hashimoto, T.; Kimura, H.; Nakatsu, H.; Mar-
uoka, K. J. Org. Chem. 2011, 76, 6030e6037; (i) Hashimoto, T.; Omote, M.; Maruoka,
K. Angew. Chem., Int. Ed. 2011, 50, 3489e3492; (j) Hashimoto, T.; Omote, M.;
Maruoka, K. Angew. Chem., Int. Ed. 2011, 50, 8952e8955; (k) Hashimoto, T.; Ki-
mura, H.; Kawamata, Y.; Maruoka, K. Nat. Chem. 2011, 3, 642e646.
m), 1.75 (2H, m), 1.60 (1H, m), 1.37 (1H, m), 1.05 (1H, m), 0.98 (3H, d,
J¼6.8 Hz), 0.95 (3H, d, J¼6.8 Hz); 13C NMR (100 MHz, CDCl3)
d 214.2,
52.1, 48.2, 43.0, 35.9, 32.5, 30.8, 24.4, 24.2; IR (neat) 2954, 1699,
1456 cmꢀ1; HRMS (ESI) exact mass calcd for C9H16O: m/z 163.1093
([MþNa]þ), found: m/z 163.1092 ([MþNa]þ); GLC analysis: Chirasil-
DEX CB (25 mꢂ0.25 mm) column (100 ꢁC isotherm, N2: 80 kPa, He:
80 kPa), retention time 11.6 min (minor) and 12.3 min (major); ½a D32
ꢃ
60.4 (c 1.07, CHCl3 (65% ee)).
9. (a) Zhang, Q. W.; Fan, C. A.; Zhang, H. J.; Tu, Y. Q.; Zhao, Y. M.; Gu, P.; Chen, Z. M.
Angew. Chem., Int. Ed. 2009, 48, 8572e8574; (b) Liang, T.; Zhang, Z.; Antilla, J. C.
Angew. Chem., Int. Ed. 2010, 49, 9734e9736.
4.5. Preparation of ethyl (1S,5S)-1-benzyl-2-oxo-5-phenylcycl
oheptanecarboxylate (6)
10. CCDC 868829 (cis-2a) and CCDC 868830 (cis-2h) contain the supplementary
crystallographic data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
11. (a) Krapcho, A. P.; Glynn, G. A.; Grenon, B. J. Tetrahedron Lett. 1967, 8, 215e217;
(b) Elsinger, F. In Organic Syntheses; Wiley: New York, 1973; Collect. Vol. 5,
pp 76e81.
12. Ube, H.; Fukuchi, S.; Terada, M. Tetrahedron: Asymmetry 2010, 21, 1203e1205.
13. Hiroya, K.; Ogasawara, K. J. Chem. Soc., Chem. Commun. 1995, 2205e2206.
14. Ooi, T.; Uematsu, Y.; Maruoka, K. J. Org. Chem. 2003, 68, 4576e4578.
To a solution of (R)-1e (0.005 mmol, 3.3 mg) in toluene (1.0 mL)
and H2O (0.10 mmol, 1.8 mL) was added cis-2a (0.10 mmol, 28.8 mg)
at ꢀ40 ꢁC and stirred for 48 h at ꢀ40 ꢁC. The mixture was then
allowed to warm to room temperature. To this solution were added
benzyl bromide (0.15 mmol, 18
and 1 M aqueous KOH (0.2 mmol, 200
room temperature, the resulting solution was quenched with
mL), Bu4NBr (0.02 mmol, 6.4 mg)
mL). After stirring for 12 h at