Synthesis of a camphor-derived auxiliary and the application to the asymmetric Darzens reaction

Article abstract of DOI:10.3184/174751913X13737254410429

A readily available chiral camphor-derived auxiliary was synthesised through a highly efficient and short general route. The Darzens reaction of the auxiliary with aldehydes in the presence of base gave glycidic esters with almost complete diastereocontro

Full text of DOI:10.3184/174751913X13737254410429

JOURNAL OF CHEMICAL RESEARCH 2013
RESEARCH PAPER 531
SEPTEMBER, 531–534
Synthesis of a camphor-derived auxiliary and the application to the
asymmetric Darzens reaction
Yamu Xia, Haixin Liu* and Xiaoli Dai
College of Chemical Engineering, Qingdao University of Science andTechnology, Qingdao 266042, P. R. China
A readily available chiral camphor-derived auxiliary was synthesised through a highly efficient and short general
route. The Darzens reaction of the auxiliary with aldehydes in the presence of base gave glycidic esters with almost
complete diastereocontrol and high yield.
Keywords: Camphor-derived auxiliary, Darzens reaction, diastereoselectivity
Glycidic esters are very important synthetic intermediates
because of their rich and useful functionality.1–4 However, few
methods exist for their synthesis in a concise and highly selec-
tive manner.5–8 The most direct method to date is an asymmet-
ric Darzens reaction9 and good ee’s or de’s have been achieved
by employing chiral auxiliaries or chiral reagents although
in all of these processes two separate steps are required: an
aldol-type reaction followed by ring closure.10 Ghosh reported11
the Darzens reaction using a chloroacetate derivative as a chiral
auxiliary gave products in high stereoselectivity. The regiose-
lective reaction of dichloromethyloxazoline with nitrobenzene
under basic conditions using t-BuOK followed by trapping
with carbonyl compounds, permitted a product to be obtained
with high selectivity.12 The aza-Darzens reaction of lithium
diethyl iodomethylphosphonate with enantiopure N-(2,4,6-
trimethylphenylsulfinyl)imines affords a single diastereomeric
N-sulfinylaziridine 2-phosphonate which, on treatment with
MeMgBr, givesthecorrespondingNH-aziridine2-phosphonate
chiral building blocks.13
Recently, the Darzens reaction using camphor derivatives as
chiral auxiliaries has received general attention.14,15 It has been
discovered that amide stabilised sulfur ylides bearing a readily
available chiral camphor-derived moiety react with aldehydes
in the presence of base to give glycidic amides directly with
complete diastereocontrol and almost complete control of
enantioselectivity.16 Bonner and Thornton established that a
conformationally rigid camphor-derived N-propionyloxazolid-
inoneeffectsasymmetricstereochemicalcontrolinsyn-selective
aldol condensations of the derived lithium and titanium
enolates with a variety of aldehydes, and a product was synthe-
sised with high stereoselectivity.17 Palomo reported that (1R)-
2-endo-bromoacetyl-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol
(endo-2-bromoacetylisoborneol) and it’s trimethylsilyl ether
are efficient reagents for the asymmetric Darzens reaction.
From the α,β-epoxy ketone adducts the chiral inductor,
camphor is removed, by treatment with ceric ammonium
nitrate, to yield the corresponding epoxy acids which are
isolated as their dicyclohexylammonium salts.18
camphor as starting material through a short general route.
Finally, the reaction of the auxiliary with aldehydes in the
presence of base gave glycidic esters with almost complete
diastereocontrol and high yield.
Results and discussion
Initially, we followed Bartlett’s conditions using camphor as
starting material through sulfonation, acylation and oxidation
to afford compound 1.19 Subsequently, the Grignard reaction of
compound 1 with PhMgBr gave compound 2, and compound 2
was methylated with CH3I in THF to give compound 3 and
then reduction of 3 with LiAlH4 gave compound 4 in high
yield.20 Ultimately, compound 5 was obtained through the
reaction of compound 4 with chloroacetyl chloride (Scheme 1).
The Darzens reaction of compound 5 with aldehydes was
studied through a series of experiments (Table 1).
As shown in Table 1, aldehydes 1, 7, 13, 19, 25 and 31 were
chosen to react with compound 5. CH3CH2ONa, NaH, t-BuOK
and LDA were used to investigate the effect of the base, and
only LDA had a better effect. Furthermore, the temperature
plays an important role in the reaction. It should be pointed out
that products were obtained with higher selectivity when the
reaction was conducted at a lower temperature. Higher tem-
peratures might speed up the reaction, but could lead to lower
stereoselectivity and more by-products. When the reaction was
conducted at −78 °C, the best result was achieved with a 99%
level of selectivity with a 95% isolated yield (entry 16). Finally,
the structure of aldehydes has an important impact on the
reaction. The reaction rate of aldehydes with electron-donating
groups is slower than aldehydes with a halogen group, but the
stereoselectivity of the former is higher. However, we obtained
products with high selectivity when we used aldehydes 1, 7,
13, 19, 25 and 31.
The compound 5 reacted with aldehydes via transition states
5B and 5B’to give glycidic esters with high diastereoselectivity.
A proposed mechanism is shown in Scheme 2. This step
involves the formation of an enol, which functions as a nucleo-
phile. Compound 5 will react with LDA through a transition
state which leads only to the (E)-enolate (5A). This enolate
reacts with aldehydes through a six-membered chair-like
transition state to afford glycidic esters with high selectivity.
In the cyclic transition state, the avoidance of the destabilising
1,3-diaxial interactions is the controlling factor. Finally, a
The asymmetric Darzens reaction using a camphor deriva-
tive as a chiral auxiliary was studied through a series of exper-
iments, and the control ability of the auxiliary in the Darzens
reaction was tested. The chiral auxiliary was synthesised using
Scheme 1 Synthesis of compound 5.
* Correspondent. E-mail: hdliuhaixin@126.com

532 JOURNAL OF CHEMICAL RESEARCH 2013
Table 1 Effects of aldehydes, temperature, base and time on yield and structures of the products
Aldehyde
R
Temp./°C
Base
Time/h
Yield/%
Compound 6:7 Major, Minor product
1
2
3
4
5
6
–78
–78
–78
–78
–40
–20
CH3CH2ONa
NaH
t-BuOK
LDA
-
-
-
-
-
-
-
-
-
-
-
-
Ph
25
16
1.5
94
85
40
97:3
94:6
85:15
6a, 7a
6a, 7a
6a, 7a
LDA
LDA
7
8
–78
–78
–78
–78
–40
–20
CH3CH2ONa
NaH
t-BuOK
LDA
-
-
-
-
-
-
-
-
9
-
-
-
-
o-ClC6H4
10
11
12
15
10
1
95
86
44
93:7
89:11
87:13
6b, 7b
6b, 7b
6b, 7b
LDA
LDA
13
14
15
16
17
18
–78
–78
–78
–78
–40
–20
CH3CH2ONa
NaH
t-BuOK
LDA
-
-
-
-
-
-
-
-
-
-
-
-
2-Thienyl
35
22
3
95
84
37
>99:1
96:4
94:6
6c, -
6c, -
6c, -
LDA
LDA
19
20
21
22
23
24
–78
–78
–78
–78
–40
–20
CH3CH2ONa
NaH
t-BuOK
LDA
-
-
-
-
-
-
-
-
-
-
-
-
4-Benzyloxy-3,5-
dimethoxyphenyl
30
21
2
93
81
37
98:2
95:5
87:13
6d, 7d
6d, 7d
6d, 7d
LDA
LDA
25
26
27
28
29
30
–78
–78
–78
–78
–40
–20
CH3CH2ONa
NaH
t-BuOK
LDA
-
-
-
-
-
-
-
-
-
-
-
-
Cinnamyl
Pentyl
25
17
1.5
94
82
35
96:4
93:7
77:23
6e, 7e
6e, 7e
6e, 7e
LDA
LDA
31
32
33
34
35
36
–78
–78
–78
–78
–40
–20
CH3CH2ONa
NaH
t-BuOK
LDA
-
-
-
-
-
-
94
83
42
-
-
-
-
-
-
27
19
1.5
97:3
95:5
86:14
6f, 7f
6f, 7f
6f, 7f
LDA
LDA
exo-10,10-Diphenyl-10-methoxymethyl-7,7-dimethylbicyclo[2.2.1]
heptyl-2-chloroacetate (5):A mixture of compound 4 (2.7 g, 8.04 mmol)
and THF (50 mL) at 0 °C was added to a solution of chloroacetyl
chloride (1.35 g, 11.9 mmol) in THF (30 mL). It was stirred for 20 min
and triethylamine was added into the mixture. The reaction was
put away from light until TLC revealed the absence of 4. Then the
reaction was quenched with NaHCO3 aqueous solution, extracted with
ethyl acetate, washed (brine), and dried over MgSO4. Concentration
in vacuo and flash column chromatography of the residue over silica
gel gave compound 5 (3.0 g, 90.5%) as a white crystal. M.p. 265–
268 °C, [α]D20 = +18.6 (c = 0.2, CHCl3). 1H NMR (CDCl3, 500 MHz)
δ 7.78 (d, 2H, J = 7.5 Hz, ArH), 7.58 (d, 2H, J = 7.5 Hz, ArH),
7.40−7.26 (m, 6H, ArH), 4.90 (dd, 1H, J = 8.0, 3.5 Hz, CHOCO), 3.68
(d, 1H, J = 14.5, COCHaHbCl), 3.61 (d, 1H, J = 14.5, COCHaHbCl),
2.88–2.84 (m, 1H, CH), 2.83 (s, 3H, OCH3), 1.88–1.19 and 0.99–0.96
(m, 6H, 3 × CH2), 1.09 (s, 3H, CH3), 0.61 (s, 3H, CH3). 13C NMR
(CDCl3, 125 MHz) δ 165.9, 140.3, 138.5, 131.6, 129.5, 127.5, 127.3,
127.0, 126.8, 87.4, 82.5, 61.4, 52.7, 49.9, 49.1, 40.8, 39.0, 31.5, 25.5,
23.4, 22.5. HRMS m/z 412.1797 (calcd for C25H29ClO3 412.1805).
product was obtained with high selectivity (up to 99%) and
high yield (up to 95%, entry 16, Table 1).
Experimental
All chemicals were used as supplied without further purification
unless otherwise specified. Melting points were taken on a Gallen-
kamp melting point apparatus and were uncorrected. Optical rotations
were determined on a Perkin-Elmer 341 polarimeter. 1H and 13C NMR
spectra were recorded on a BrukerAM-500 MHz spectrometer. HRMS
values were measured by a JEOL JMS-SX or JEOL JMS-SX 102A
spectrometer. Flash column chromatography was performed on silica
gel (200–300 mesh) (Qingdao Haiyang Chemical Co. Ltd, China) and
TLC measurements were performed on silica gel GF254 plates
(Qingdao Haiyang Chemical Co. Ltd, P.R. China).
Ketopinic acid methyl ester (1), exo-10,10-diphenyl-10-hydroxy-
methyl-7,7-dimethylbicyclo[2.2.1]heptane-2-one (2), exo-10,10-
diphenyl-10-methoxymethyl-7,7-dimethylbicyclo[2.2.1]heptane-2-one
(3) and exo-10,10-diphenyl-10-methoxymethyl-7,7-dimethylbicyclo-
[2.2.1]heptane-2-ol (4) were synthesised according to the procedure
which has been described previously.

JOURNAL OF CHEMICAL RESEARCH 2013 533
Scheme 2 A proposed mechanism for the synthesis of compound 6 and 7.
General procedure for the preparation of 6 and 7
NMR (CDCl3, 125 MHz) δ 166.8, 140.7, 140.1, 139.0, 133.8, 133.6,
131.6, 129.9, 129.8, 129.3, 128.7, 127.6, 127.5, 127.1, 126.7, 87.7,
82.6, 61.5, 56.7, 55.8, 55.3, 52.7, 50.2, 49.1, 39.5, 31.3, 23.4, 22.8.
HRMS m/z 516.2076 (calcd for C32H33ClO4 516.2067).
6a and 7a:A mixture of compound 5 (0.2 g, 0.48 mmol) and anhydrous
THF (10 mL) was dropped into a solution of LDA (53.5 mmg,
0.5 mmol) in anhydrous THF (10 mL) at −78 °C under N2, then
benzaldehyde (0.08 mL, 0.75 mmol) was added, the mixture was
stirred until TLC revealed the absence of benzaldehyde, the mixture
was quenched with saturated NH4Cl (5 mL), extracted with ethyl ace-
tate, washed (saturated NaHSO3 and NaCl), and dried over MgSO4.
Concentration in vacuo and flash column chromatography of the
residue over silica gel (100 mL) using hexane/ethyl acetate (99:1)
gave compound 6a (0.18 g, 78%) as a pale yellow oil and then 7a as
6c: [α]D20 = +15.6 (c = 0.01, CHCl3). 1H NMR (CDCl3, 500 MHz)
δ 7.78–7.76 (m, 2H, ArH), 7.50–7.19 (m, 9H, ArH), 7.19 (d, 1H,
J = 3.5 Hz, CHCH=CH), 7.07 (dd, 1H, J = 5.0, 4.0 Hz, C=CHCH=CH),
6.29 (d, 1H, J = 2.0 Hz, COCH), 5.82 (d, 1H, J = 2.0 Hz, OCOCH),
4.84 (dd, 1H, J = 8.0, 3.0 Hz, CHOCO), 2.82 (s, 3H, OCH3), 2.70–
2.55 (m, 1H, CH), 1.81–1.54 and 0.90–0.64 (m, 6H, 3 × CH2), 1.27 (s,
3H, CH3), 1.17 (s, 3H, CH3). 13C NMR (CDCl3, 125 MHz) δ:164.2,
139.3, 139.2, 137.5, 136.9, 131.3, 129.7, 129.1, 128.1, 127.4, 127.3,
127.1, 126.9, 105.9, 88.5, 82.8, 60.8, 53.1, 52.6, 50.7, 48.9, 39.0, 31.3,
25.1, 23.7, 23.6. HRMS m/z 488.2012 (calcd for C30H32O4S
488.2021).
20
1
a white oil. 6a: [α]D = +14.6 (c = 0.01, CHCl3). H NMR (CDCl3,
500 MHz) δ 7.79–7.77 (m, 2H, ArH), 7.63–7.60 (m, 2H, ArH), 7.42–
7.25 (m, 8H, ArH), 7.13–7.11 (m, 3H, ArH), 4.96 (dd, 1H, J = 8.5,
3.5 Hz, CHOCO), 3.72 (d, 1H, J = 2.0 Hz, OCHAr), 3.18 (d, 1H,
J = 2.0 Hz, OCOCH), 2.99–2.97 (m, 1H, CH), 2.75 (s, 3H, OCH3),
1.91–1.38 and 1.05–0.97 (m, 6H, 3 × CH2), 1.08 (s, 3H, CH3), 0.43 (s,
3H, CH3). 13C NMR (CDCl3, 125 MHz) δ 166.8, 140.3, 138.0, 135.0,
131.7, 129.7, 129.1, 128.7, 127.5, 127.2, 126.8, 126.6, 125.9, 87.1,
6d and 7d. 6d: [α]D20 = +68.1 (c = 0.01, CHCl3). 1H NMR (CDCl3,
500 MHz) δ 7.85 (d, 2H, J = 8.0 Hz, ArH), 7.59 (d, 2H, J = 8.0 Hz,
ArH), 7.49–7.41 (m, 3H, ArH), 7.36–7.11 (m, 8H, ArH), 6.40 (s, 2H,
ArH), 5.00 (s, 2H, ArCH2), 4.99–4.97 (m, 1H, CHOCO), 3.84 (s, 6H,
2 × OCH3), 3.47 (d, 1H, J = 1.5 Hz, OCHAr), 3.04 (d, 1H, J = 2.0 Hz,
OCOCH), 2.91–2.85 (m, 1H, CH), 2.78 (s, 3H, ArCOCH3), 1.93–1.15
and 1.01–0.95 (m, 6H, 3 × CH2), 1.09 (s, 3H, CH3), 0.61 (s, 3H, CH3).
13C NMR (CDCl3, 125 MHz) δ 167.1, 153.8, 140.6, 138.9, 138.3,
137.5, 137.2, 131.6, 130.7, 129.9, 128.5, 128.2, 128.0, 127.6, 127.1,
126.9, 126.6, 106.6, 102.5, 87.4, 82.6, 75.1, 61.3, 57.2, 56.8, 56.2,
56.1, 52.5, 49.8, 49.2, 39.4, 31.7, 25.6, 23.5, 22.5. HRMS m/z
648.3096 (calcd for C41H44O7 648.3087). 7d: [α]D20 = −52.6 (c = 0.005,
CHCl3). 1H NMR (CDCl3, 500 MHz) δ 7.82 (d, 2H, J = 8.0 Hz, ArH),
7.61 (d, 2H, J = 8.0 Hz, ArH), 7.51–7.43 (m, 3H, ArH), 7.35–7.10 (m,
8H, ArH), 6.47 (s, 2H, ArH), 5.04 (s, 2H, ArCH2), 4.97–4.95 (m, 1H,
CHOCO), 3.83 (s, 6H, 2 × OCH3), 3.69 (d, 1H, J = 1.5 Hz, OCHAr),
3.12 (d, 1H, J = 2.0 Hz, OCOCH), 2.93–2.87 (m, 1H, CH), 2.77 (s,
3H, ArCOCH3), 1.96–1.16 and 1.03–0.97 (m, 6H, 3 × CH2), 1.06 (s,
3H, CH3), 0.42 (s, 3H, CH3). 13C NMR (CDCl3, 125 MHz) δ:167.0,
153.9 140.5, 138.8, 138.2, 137.4, 137.1, 131.7, 130.7, 130.0, 128.4,
128.1, 127.9, 127.7, 127.2, 127.0, 126.8, 106.5, 102.5, 87.4, 82.4,
75.1, 61.4, 57.2, 56.8, 56.2, 56.1, 53.5, 49.6, 49.1, 39.3, 31.3, 25.7,
23.6, 22.6. HRMS m/z 648.3092 (calcd for C41H44O7 648.3087).
6e and 7e. 6e: [α]D20 = −21.8 (c = 0.01, CHCl3). 1H NMR (CDCl3,
500 MHz) δ 7.85–7.75 (m, 4H, ArH), 7.57–7.23 (m, 11H, ArH), 6.80
(d, 1H, J = 5Hz, CH=CHAr), 6.58 (d, 1H, J = 5.0 Hz, CH=CHAr),
4.90–4.89 (m, 1H, CHOCO), 3.64 (d, 1H, J = 1.5 Hz, CHCH=CH),
3.42 (d, 1H, J = 2 Hz, OCOCH), 2.90–2.83 (m, 1H, CH), 2.80 (s, 3H,
OCH3), 1.86–1.16 and 0.96–0.94 (m, 6H, 3 × CH2), 1.08 (s, 3H, CH3),
0.59 (s, 3H, CH3). 13C NMR (CDCl3, 125 MHz) δ 169.5, 140.2, 139.5,
136.7, 131.5, 130.7, 129.7, 129.4, 128.9, 128.6, 127.4, 126.9, 126.7,
123.0, 86.9, 82.7, 62.5, 52.6, 49.8, 49.0, 40.5, 39.6, 31.4, 29.6, 25.4,
23.3, 22.4, 14.9. HRMS m/z 508.2619 (calcd for C34H36O4 508.2614).
82.1, 61.6, 57.7, 56.8, 52.6, 49.6, 49.1, 39.2, 31.3, 25.7, 22.8, 22.0.
HRMS m/z 482.2448 (calcd for C32H34O4 482.2457). 7a: [α]D
20
=
+18.3 (c = 0.01, CHCl3). 1H NMR (CDCl3, 500 MHz) δ 7.82–7.79 (m,
2H, ArH), 7.62–7.59 (m, 2H, ArH), 7.43–7.26 (m, 8H, ArH), 7.14–
7.12 (m, 3H, ArH), 4.97 (dd, 1H, J = 8.5, 3.5 Hz, CHOCO), 3.59 (d,
1H, J = 2.0 Hz, OCHAr), 3.08 (d, 1H, J = 2.0 Hz, OCOCH), 3.01–2.99
(m, 1H, CH), 2.79 (s, 3H, OCH3), 1.93–1.39 and 1.06–0.98 (m, 6H,
3 × CH2), 1.09 (s, 3H, CH3), 0.60 (s, 3H, CH3). 13C NMR (CDCl3,
125 MHz) δ:166.9, 140.3, 138.1, 135.1, 131.9, 129.9, 129.2, 128.8,
127.5, 127.2, 126.9, 126.6, 125.9, 86.9, 82.3, 61.0, 57.8, 56.9, 52.8,
49.7, 49.2, 39.2, 31.3, 25.8, 22.9, 22.0. HRMS m/z 482.2450 (calcd
for C32H34O4 482.2457).
All the other products are given by analogy (6b and 7b; 6c; 6d and
7d; 6e and 7e; 6f and 7f).
6b and 7b. 6b: [α]D20 = −48.5 (c = 0.01, CHCl3). 1H NMR (CDCl3,
500 MHz) δ 7.85–7.79 (m, 2H, ArH), 7.71–7.68 (m, 2H, ArH),
7.43–7.02 (m, 10H, ArH), 4.89–4.85 (m, 1H, CHOCO), 4.04 (d, 1H,
J = 1.5 Hz, CHCHC), 3.95 (d, 1H, J = 1.5 Hz, OCOCH), 2.90–2.83
(m, 1H, CH), 2.81 (s, 3H, OCH3), 1.66–1.41 and 1.11–1.01 (m, 6H,
3 × CH2), 1.11 (s, 3H, CH3), 0.79 (s, 3H, CH3). 13C NMR (CDCl3,
125 MHz) δ 166.6, 140.1, 139.8, 138.8, 133.5, 133.3, 131.5, 129.7,
129.6, 129.2, 128.7, 127.5, 127.4, 127.0, 126.8, 87.6, 82.4, 61.1, 56.3,
55.8, 55.2, 52.6, 50.1, 48.9, 39.2, 31.2, 23.3, 22.7. HRMS m/z
20
516.2075 (calcd for C32H33ClO4 516.2067). 7b: [α]D = +26.5 (c =
0.01, CHCl3). 1H NMR (CDCl3, 500 MHz) δ 7.87–7.81 (m, 2H, ArH),
7.73–7.70 (m, 2H, ArH), 7.44–7.04 (m, 10H, ArH), 4.92–4.89 (m, 1H,
CHOCO), 4.04 (d, 1H, J = 1.5 Hz, CHCHC), 3.94 (d, 1H, J = 1.5 Hz,
OCOCH), 2.89–2.82 (m, 1H, CH), 2.83 (s, 3H, OCH3), 1.67–1.42 and
1.13–1.03 (m, 6H, 3 × CH2), 1.13 (s, 3H, CH3), 0.82 (s, 3H, CH3). 13
C

534 JOURNAL OF CHEMICAL RESEARCH 2013
20
1
7e: [α]D = +30.4 (c = 0.005, CHCl3). H NMR (CDCl3, 500 MHz)
δ 7.86–7.76 (m, 4H, ArH), 7.57–7.23 (m, 11H, ArH), 6.90 (d, 1H,
J = 5Hz, CH=CHAr), 6.46 (d, 1H, J = 5Hz, CH=CHAr), 4.87–4.85
(m, 1H, CHOCO), 3.65 (d, 1H, J = 1.5 Hz, CHCH=CH), 3.43 (d, 1H,
J = 2 Hz, OCOCH), 2.91–2.84 (m, 1H, CH), 2.81 (s, 3H, OCH3),
1.87–1.16 and 0.96–0.94 (m, 6H, 3 × CH2), 1.09 (s, 3H, CH3), 0.61 (s,
3H, CH3). 13C NMR (CDCl3, 125 MHz) δ 169.4, 140.3, 139.6, 136.8,
131.6, 130.9, 129.7, 129.5, 128.8, 128.5, 127.6, 127.1, 126.9, 123.2,
87.1, 82.9, 62.7, 53.0, 49.9, 49.2, 40.8, 39.8, 31.6, 29.9, 25.7, 23.4,
22.5, 14.8. HRMS m/z 508.2623 (calcd for C34H36O4 508.2614).
Received 20 May 2013; accepted 18 June 2013
Paper 1201912 doi: 10.3184/174751913X13737254410429
Published online: 6 September 2013
References
1
2
3
4
5
G. Lemonnier, L. Zoute, J.C. Quirion and P. Jubault, Org. Lett., 2010, 12,
844.
M. Curini, F. Epifano, M.C. Marcotullio and O. Rosati, Eur. J. Org. Chem.,
2002, 9, 1562.
M.V. Reddy, S.V. Pitre, I. Bhattacharya and Y.D. Vankar, Synlett., 1996, 3,
241.
M. Mamaghani, K. Tabatabaeian, A. Ghanadzadeh and F. Habibi,
Tetrahedron Lett., 2003, 44, 4775.
E.N. Jacobsen, L. Deng, Y. Furukawa and L.E. Martinez, Tetrahedron,
1994, 50, 4323.
20
1
6f and 7f. 6f: [α]D = +52.3 (c = 0.01, CHCl3). H NMR (CDCl3,
500 MHz) δ 7.93 (d, 2H, J = 10 Hz, ArH), 7.68 (d, 2H, J = 10 Hz,
ArH), 7.42–7.26 (m, 6H, ArH), 4.92–4.91 (m, 1H, CHOCO), 3.12–
3.02 (m, 1H, CH), 2.96 (d, 1H, J = 1.5 Hz, OCHCH2), 2.82 (d, 1H,
J = 2.0 Hz, OCOCH), 2.80 (s, 3H, CH3), 1.96–1.57, 1.53–1.46 and
0.98–0.87 (m, 6H, 3 × CH2), 1.57–1.54 (m, 2H, OCHCH2CH2), 1.44–
1.37 (m, 2H, CH2CH2CH3), 1.34–1.28 (m, 2H, CH2CH2CH2), 1.06 (s,
3H, CH3), 0.99 (s, 3H, CH2CH3), 0.37 (s, 3H, CH3). 13C NMR (CDCl3,
125 MHz) δ 167.8, 140.4, 138.3, 131.9, 129.7, 127.4, 127.2, 126.8,
126.6, 86.9, 82.0, 61.6, 58.1, 53.0, 52.6, 49.4, 49.1, 39.2, 31.2, 31.1,
27.8, 25.8, 22.8, 22.4, 21.7, 13.9. HRMS m/z 462.2764 (calcd for
C30H38O4 462.2770). 7f: [α]D = +55.6 (c = 0.005, CHCl3). H NMR
(CDCl3, 500 MHz) δ 7.87 (d, 2H, J = 10 Hz, ArH), 7.61 (d, 2H, J =
10 Hz, ArH), 7.41–7.25 (m, 6H, ArH), 4.91–4.90 (m, 1H, CHOCO),
3.11–3.01 (m, 1H, CH), 2.94 (d, 1H, J = 1.5 Hz, OCHCH2), 2.81 (d,
1H, J = 2.0 Hz, OCOCH), 2.80 (s, 3H, CH3), 1.97–1.58, 1.54–1.47
and 0.97–0.86 (m, 6H, 3 × CH2), 1.58–1.55 (m, 2H, OCHCH2CH2),
1.45–1.38 (m, 2H, CH2CH2CH3), 1.35–1.29 (m, 2H, CH2CH2CH2),
1.10 (s, 3H, CH3), 1.01 (s, 3H, CH2CH3), 0.38 (s, 3H, CH3). 13C NMR
(CDCl3, 125 MHz) δ 167.6, 140.5, 138.9, 131.5, 129.6, 127.5, 127.1,
126.9, 126.6, 87.8, 82.4, 61.4, 57.7, 53.0, 52.7, 49.5, 49.0, 39.3, 31.3,
31.2, 28.4, 26.9, 22.9, 22.5, 21.8, 14.0. HRMS m/z 462.2761 (calcd
for C30H38O4 462.2770).
6
7
8
M.J. Porter and J. Skidmore, Chem. Commun., 2000, 1215.
O.M. Cohn, D. Williams and Y. Chen, Chem. Commun., 2000, 495.
T. Nemoto, T. Ohshima and M. Shibasaki, J. Am. Chem. Soc., 2001, 123,
9474.
9
T. Rosen, B.M. Trost, I. Fleming and C.H. Heathcock, Compr. Org. Synth.,
20
1
1991, 2, 409.
10 S. Arai, T. Suzuki, K. Tokumaru and T. Shioiri, Tetrahedron Lett., 2002, 43,
833.
11 A.K. Ghosh and J.H. Kim, Org. Lett., 2004, 6, 2725.
12 S. Florio, P. Lorusso, C. Granito, R. Luisi and L. Troisi, J. Org. Chem.,
2004, 69, 4961.
13 F.A. Davis, T. Ramachandar and Y. Wu, J. Org. Chem., 2003, 68, 6894.
14 Y. Cheng, H. Wu, P. Wu, Y. Shen and B. Uang, Chem-Asian J., 2012, 7,
2921.
15 J. Weng, H.B. Ai, R.S. Luo and G. Lu, Chirality, 2012, 24, 271.
16 V.K. Aggarwal, G. Hynd, W. Picoul and J.L. Vasse, J. Am. Chem. Soc.,
2002, 124, 9964.
17 M.P. Bonner and E.R. Thornton, J. Am. Chem. Soc., 1991, 113, 1299.
18 C. Palomo, M. Oiarbide, A.K. Sharma, M.C. Gonzalez, A. Linden,
J.M. Garcia and A. Gonzalez, J. Org. Chem., 2000, 65, 9007.
19 P.D. Bartlett and L.H. Knox, Org. Synth., 1973, 5, 689.
20 Y.Y. Chu, C.S. Yu, C.J. Chen, K.S. Yang, J.C. Lain, C.H. Lin and
K. Chen, J. Org. Chem., 1999, 64, 6993.
This work was supported by the National Natural Science
Foundation of Shandong (No. ZR2010HM023), the Chinese
Medicine Administration Bureau of Gansu Province (No.
GZK-2011-62).

Copyright of Journal of Chemical Research is the property of Science Reviews 2000 Ltd. and
its content may not be copied or emailed to multiple sites or posted to a listserv without the
copyright holder's express written permission. However, users may print, download, or email
articles for individual use.