Enantioselective Synthesis of Arene cis-Dihydrodiols from 2-Pyrones

Article abstract of DOI:10.1002/anie.201908284

An enantioselective chemical synthesis of arene cis-dihydrodiols has been realized from 2-pyrones through sequential ytterbium-catalyzed asymmetric inverse-electron-demand Diels–Alder (IEDDA) reaction of 2-pyrones and retro-Diels–Alder extrusion of CO₂. By using this strategy, a series of substituted arene cis-dihydrodiols can be obtained efficiently with high enantioselectivity (>99 % ee in many cases). Based on this strategy, efficient and concise asymmetric total syntheses of (+)-MK7607 and 1-epi-(+)-MK7607 were accomplished.

Full text of DOI:10.1002/anie.201908284

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
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Accepted Article
Title: Enantioselective Synthesis of Arene cis-Dihydrodiols from 2-
Pyrones
Authors: Quan Cai, Xiaowei Liang, Yunlong Zhao, Xuge Si, Mengmeng
Xu, Jiahao Tan, Zhimao Zhang, Chenggong Zheng, and Chao
Zheng
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201908284
Angew. Chem. 10.1002/ange.201908284
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10.1002/anie.201908284
Angewandte Chemie International Edition
COMMUNICATION
Enantioselective Synthesis of Arene cis-Dihydrodiols from 2-
Pyrones
Xiao-Wei Liang†, Yunlong Zhao†, Xu-Ge Si, Meng-Meng Xu, Jia-Hao Tan, Zhi-Mao Zhang, Cheng-
Gong Zheng, Chao Zheng, and Quan Cai*
In memory of Prof. István E. Markó and Prof. Gary H. Posner
Abstract: The enantioselective chemical synthesis of arene cis-
dihydrodiols has been realized from 2-pyrones by sequential
ytterbium-catalyzed asymmetric inverse-electron-demand Diels–
Alder (IEDDA) reaction of 2-pyrones and retro Diels–Alder extrusion
of CO2. According to this strategy, a series of substituted arene cis-
dihydrodiols can be obtained efficiently with high enantioselectivities
(> 99% ee in many cases). Based on this strategy, efficient
asymmetric total syntheses of (+)-MK7607, 1-epi-(+)-MK7607 have
been accomplished in a concise manner.
challenge. To the best of our knowledge, only one approach has
been reported to date, which was based on the chiral pool
strategy.[10] In 2009, Metz and Sun realized an elegant
enantioselective synthesis of an arene cis-dihydrodiol triflate
derivative from D-ribose in nine steps.[10] Taken together, a finely
tuned synthetic approach for the catalytic, asymmetric chemical
synthesis of arene cis-dihydrodiols, complete with easy
accessibility to both enantiomers, broad functional group
tolerance and excellent levels of enantioselectivity, would
represent an enabling technology for the construction of complex
molecules and a welcome complementation to the synthetic
community.
Arene cis-dihydrodiols, produced by bacterial dioxygenase-
catalyzed asymmetric dihydroxylation of arenes,[1] are very
attractive chiral synthons due to the easily convertible
cyclohexadiene and cis-diol functionalities in the molecular
skeletons (Scheme 1a). The synthetic utilities of these
metabolites were initially demonstrated in the preparation of
polyphenylene by ICI in 1983,[2] the total synthesis of (±)-pinitol by
Ley in 1987,[3] and the asymmetric total synthesis of prostaglandin
E2 (PGE2α) by Hudlicky in 1988.[4] Since then, their applications
in organic synthesis have expanded rapidly, and led to elegant
chemoenzymatic syntheses of a large variety of natural products
and pharmaceuticals.[5,6]
a
Enzymatic synthesis and applications in organic synthesis of arene cis-dihydrodiols
R
R
enzymatic
dihydroxylation
OH
arene
cis-dihydrodiols
OH
OH
OH
O
MeO
HO
CO2H
OH
n
HO
OH
OH
polyphenylene
(±)-pinitol
PGE2
Despite these tremendous accomplishments and the
extraordinary synthetic potential of these arene cis-dihydrodiols,
their accessibilities are largely relied upon enzymatic
catalysis.[5e,5g,7] In contrast, chemical synthesis of these useful
metabolites has remained a great challenge owing to the inherent
difficulty to construct the cyclohexadiene subunit while accurately
controlling the relative and absolute configurations of the nascent
diol.[8] A notable breakthrough was made by Sarlah and co-
workers recently, who developed an efficient method for the
racemic synthesis of arene cis-dihydrodiols by visible light-
induced dearomative Diels–Alder reaction followed by
dihydroxylation, diol-protection, hydrolysis, oxidation and retro
Diels–Alder reaction.[9a,9b] However, the enantioselective chemical
Inspiration: Arene synthesis by Diels-Alder reaction and retro Diels-Alder reaction
from 2-pyrones
b
O
X
CO2 2[H] or HX
O
X
O
X
R2
R1
O
R1
X = C, O, N, S...
R1
R2
R2
retro Diels-Alder
followed by [O] or [-HX]
Diels-Alder
c
This work: catalytic asymmetric synthesis of arene cis-dihydrodiols from 2-pyrones
L
L
O
R2O
O
M
L
O
CO2R2
2
O
CO2R2
O
1O
CO2
3
O
O
L
O
R1
2
R1
2
6
R1
IEDDA
retro DA
O
O
1
M = Yb(OTf)3
L = modified BINOL
6
synthesis of arene cis-dihydrodiols remains
a
formidable
1
3
4
OH
OH
OH
.
.
.
.
high yields, high ee
wide substrate scope
OH
OH
]
[*]
Dr. X.-W. Liang,[† Y. Zhao,[†] X.-G. Si, M.-M. Xu, J.-H. Tan, Z.-M.
cascade reaction for
6-substituted pyrones
Zhang, C.-G. Prof. Dr. Q. Cai
OH
HO
HO
Department of Chemistry and Research Center for Molecular
Recognition and Synthesis, Fudan University
220 Handan Rd., Shanghai 200433, China
E-mail: quan_cai@fudan.edu.cn
OH
(+)-MK7607
OH
1-epi-(+)-MK7607
highly valuable in natural
product syntheses
Prof. Dr. C. Zheng
Scheme 1. Enzymatic synthesis and our strategy for the enantioselective
synthesis of arene cis-dihydrodiols.
State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences
345 Lingling Rd., Shanghai 200032, China
These authors contributed equally to this work.
[†]
Inspired by the efficient syntheses of aromatics from 2-pyrones,
which proceeded via Diels–Alder reaction with an electron-rich
Supporting information for this article is given via a link at the end of the
document.((Please delete this text if not appropriate))
This article is protected by copyright. All rights reserved.

10.1002/anie.201908284
Angewandte Chemie International Edition
COMMUNICATION
Table 1. Strategy investigations.
alkene, followed by a retro Diels–Alder reaction, and spontaneous
oxidation or elimination (Scheme 1b),[11] we have developed an
unprecedented enantioselective synthetic strategy for accessing
arene cis-dihydrodiols (Scheme 1c). This strategy involves an
ytterbium-catalyzed enantioselective inverse-electron–demand
Diels-Alder (IEDDA) reaction of 3-carboalkoxyl-2-pyrones 1 with
dienophile 2,2-dimethyl-1,3-dioxole 2 and a retro Diels–Alder
extrusion of CO2 from intermediates 3. Based on this strategy, a
wide range of arene cis-dihydrodiols 4 were afforded in high yields
and ee. Moreover, the enantioenriched product could readily
deliver bioactive natural products (+)-MK7607 and its analog1-
epi-(+)-MK7607 in a concise manner. Herein, we report the
results of this study.
We began our studies with the development of the catalytic
enantioselective IEDDA reaction of 2-pyrone and 2,2-dimethyl-
1,3-dioxole. Encouraged by the pioneering works about the
enantioselective Diels-Alder reaction of 2-pyrone[12] with vinyl
ethers reported by Marko[13] and Posner,[14] we therefore
evaluated the Diels–Alder reaction of 2-pyrone 1a and 2,2-
dimethyl-1,3-dioxole 2 in the presence of Yb(OTf)3 (20 mol%) and
(R)-BINOL L1 (24 mol%).[13,15] Indeed, the desired cycloadduct 3a
was obtained, but with moderate yield and ee (58% yield, 40% ee,
Table 1a, entry 1). The low reactivity was consistent with the
observations in the literatures that 2,2-dimethyl-1,3-dioxole 2 was
a much weaker dienophile than vinyl ethers in IEDDA reaction
because of its unpolarized electronic properties.[16] We envisaged
that the introduction of electron-withdrawing groups on the 3,3’-
positions of the BINOL backbone would increase the Lewis acidity
of the catalyst, and may also benefit the stereocontrol. To our
delight, after extensive studies (Table 1a, entries 2-7),[17] we found
the utilization of L7, bearing pentafluorophenyl moieties, led to 3a
with dramatically improved yield and enantioselectivity (85% yield,
98% ee, > 20:1 dr, entry 7). Notably, lower catalyst loading (10
mol%) was tolerated, providing 3a in 87% yield and 98% ee (entry
8).
With bicyclic lactone 3a with 98% ee in hand, we then examined
the reaction conditions for the retro Diels–Alder extrusion of
CO2.[18] The key to the success of this step was the development
of mild reaction conditions to avoid side reactions for the labile
product 4a (for example, aromatization, dimerization, or 6π-
electronic cyclization, which would erode the yield and ee of the
product). It was found that subjecting 3a in refluxing toluene
afforded benzoate ester 2,3-cis-dihydrodiol 4a in 26% yield and
93% ee (Table 1b, entry 1). The isolation of 5a (70% yield, > 99%
ee) indicated the low yield of 4a was caused by dimerization. Thus,
to prevent this dimerization, we then performed the reaction at
lower concentrations (Table 2, entries 2-3). Pleasingly, when the
reaction was conducted at 0.01 M (Table 1b, entry 3), 4a was
obtained in 79% yield and 98% ee. Further reaction optimization
revealed significant solvent effects (Table 1b, entries 3-8), and
chlorobenzene was found to be the best choice, affording 4a in
98% yield and 98% ee (entry 8).
a. Reaction Optimization for IEDDA reaction[a]
R
O
O
OR'
Yb(OTf)3 (20 mol%),
(R)-L (24 mol%),
CO2R'
O
O
OH
OH
DIPEA (48 mol%),
4 Å MS, DCM, 40 °C
O
O
O
O
R' = CH2CH2Ph
2
R
O
1a
3a
L
(R)-
Entry
(R)-L, R
t (h)
yield
ee (%)[c]
(%)[b]
1
2
3
4
5
6
7
8d
L1, R = H
L2, R = 2,4,6-(iPr)3-C6H2
L3, R = 9-anthryl
L4, R = SiPh3
L5, R = Cl
24
48
48
48
20
6
58
10
11
15
74
87
85
87
40
0
1
0
79
94
98
98
L6, R = Br
L7, R = C6F5
3
L7, R = C6F5
3
b. Reaction Optimization for retro Diels-Alder extrusion of CO2
O
CO2R'
O
O
CO2R'
O
CO2R'
CO2R'
O
solvent
reflux
O
O
O
+
O
O
R' = CH2CH2Ph
3a
5a
4a
Entry
solvent
Conc.
t
Yield (%)[b]
ee (%)[c]
4a/5a
(M)
(h)
4a/5a
1
2
3
4
5
6
7
8
toluene
toluene
0.1
24
24
24
24
3
26/70
56/28
79/20
trace
91
93/> 99
97/> 99
98/> 99
--
0.05
0.01
0.01
0.01
0.01
0.01
0.01
toluene
1,4-dioxane
o-xylene
m-xylene
p-xylene
ClC6H5
98
5
92
98
5
93
98
4
98
98
[a] Reaction conditions: 1a (0.2 mmol), 2 (0.6 mmol), 20 mol% Yb(OTf)3, 24
mol% (R)-L, 48 mol% DIPEA, 4 Å molecular sieves (50 mg) in DCM (1.0 mL) at
40 oC. [b] Isolated yield. [c] Enantiomeric excess was determined by HPLC on
a chiral stationary phase. [d] Yb(OTf)3 (10 mol%), (R)-L7 (12 mol%), DIPEA
(24 mol%).
substituted phenyl groups at the C4 position of 2-pyrone were also
compatible, providing 4f-4i in 89–94% ee. Furthermore, various
C5-aryl or alkyl substituted 2-pyrones were also viable substrates,
delivering the desired products 4j-4o in good yields and excellent
enantioselectivities (96–99% ee). Moreover, the Diels–Alder
reaction of brominated 2-pyrone 1p proceeded smoothly to
provide lactone 3p in 87% yield and 95% ee. Unfortunately, the
corresponding brominated diene 4p was unstable and
decomposed under the retro Diels–Alder reaction conditions. It
should be noted that the robustness and practicality of this
strategy were showcased by the gram-scale synthesis of 4h in
70% yield and 89% ee over two steps.
After the optimal reaction conditions were established, the
scope was investigated. As illustrated in Table 2a, 2-pyrones
bearing different kinds of esters were tolerated, affording lactones
3a-3e in 76–86% yields and 92–98% ee. Through retro Diels–
Alder reaction, the corresponding dienes 4a-4e were obtained in
excellent yields without erosion of ee. Substrates with various
Next, we examined the scope of 6-substituted-3-
carbomethoxyl-2-pyrones, which were challenging substrates for
the initial Diels–Alder reaction, as highly congested intermediates
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10.1002/anie.201908284
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COMMUNICATION
Table 2. Substrate scope with respect to substituted 2-pyrones.a,b,c
O
a
CO2R1
CO2R1
CO2R1
O
Conditions 1:
Yb(OTf) 3 (10 mol%), (R)-L7 (12 mol%)
DIPEA (24 mol%), 4 Å MS, DCM,40 °C
R2
R3
O
R2
O
O
R2
R3
O
Conditions 1
Conditions 2
R3
+
O
O
O
O
Conditions 2:
0.01 M, chlorobenzene, reflux
1
4
2
3
O
4a, R1 = C2H4Ph, 98%, 98% ee
4b, R1 = Me, 88%, 97% ee
4c, R1 = Et, 90%, 94% ee
CO2R1
O
3a, R1 = C2H4Ph, 86%, 98% eed
3b
3c, R1 =Et, 76%, 97% ee
3d, R1 = Allyl, 84%, 98% ee
3e, R1 = Bn, 81%, 92% ee
CO2R1
O
, R1 = Me, 85%, 97% ee
O
, R1 = Allyl, 92%, 97% ee
4d
O
4e, R1 = Bn, 95%, 91% ee
O
O
O
O
O
O
CO2Me
O
CO2Me
O
CO2Me
CO2Me
O
O
CO2Me
CO2Me
O
O
O
O
O
O
O
O
O
O
O
O
O
(gram scale )
(gram scale )
3f
, 89%, 91% ee
O
4f, 94%, 91% ee
3g, 75%, 92% ee
4g
3h, 75%, 90% ee
4h, 93%, 89% ee
, 96%, 92% ee
CO2Me
O
O
O
CO2Me
Cl
Cl
CO2Me
CO2Me
O
CO2Me
O
CO2Me
O
O
O
O
O
O
O
O
O
O
O
O
4j
3k, 95%, 99% ee
4k, 81%, 99% ee
3i, 89%, 94% ee
3j, 86%, 99% ee
, 78%, 99% ee
4i, 94%, 94% ee
CO2Me
O
O
O
CO2Et
O
CO2Me
O
CO2Me
O
CO2Et
O
CO2Me
O
O
O
O
O
O
Br
Et
Me
O
O
Me
Et
O
O
O
Br
3l, 96%, 99% ee
3m, 94%, 99% ee
4m, 85%, 98% ee
3n, 91%, 98% ee
4n, 88%, 98% ee
4l, 80%, 99% ee
O
O
CO2Me
O
CO2Me
O
CO2Me
O
CO2Me
O
O
Br
O
O
O
Br
O
O
3o, 81%, 96% ee
4o, 78%, 96% ee
3p, 87%, 95% ee
4p, unstable
b
CO2R1
O
O
CO2R1
CO2R1
O
O
2
CO2R1
R2
R3
R2
R3
O
CO2R1
R2
R3
O
R2
R3
Conditions 3
1O
R2
R3
O
O
+
O
Yb(OTf) 3 (20 mol%),
(R)-L7 (24 mol%)
DIPEA (48 mol%),
4 Å MS, DCM, 40 °C
O
6
O
O
O
O
R4
R4
O
R4
R4
R4
exo-4
ent-4
2
endo -3
4
1
CO2Me
CO2Me
CO2Me
O
CO2Me
CO2Me
O
4q, R = H, 87%, > 99% ee
4r, R = Me, 79%, > 99% ee
4s, R = OMe, 54%, > 99% ee
4t , R = F, 82%, > 99% ee
4u, R = Cl, 79%, > 99% ee
4v, R = Br, 88%, > 99% eed
4w, R = CF3, 84%, > 99% ee
O
O
O
O
O
O
O
O
O
S
R
Cl
4z, 82%, 99% ee
4x, 87%, >99% ee
4y, 35%, 99% ee
4aa, 82%, 99% ee
MeO2C
O
CO2Me
CO2Me
CO2Me
CO2Me
CO2Et
O
O
O
O
O
O
O
O
O
O
O
F
4ad, 20%, 91% eee
4ae, 88%, 99% eee
4ag
, 85%, 99% ee
e
4af, 71%, 96% eee
4ab, 27%, 92% ee
4ac
, 60%, > 99% ee
[a] Reaction conditions 1: 1 (0.2 mmol), 2 (0.6 mmol), 10 mol% Yb(OTf)3, 12 mol% (R)-L7, 24 mol% DIPEA, 4 Å molecular sieves (50 mg) in DCM (1.0 mL) at 40
oC; Reaction conditions 2: 3 (0.1 mmol) in chlorobenzene (0.01 M) at reflux; Reaction conditions 3: 1 (0.2 mmol), 2 (0.6 mmol), Yb(OTf)3 (20 mol%), (R)-L7 (24
mol%), DIPEA (48 mol%), 4 Å molecular sieves (50 mg) in DCM (1.0 mL) at 40 oC. [b] Isolated yield. [c] Enantiomeric excess was determined by HPLC on a
chiral stationary phase. [d] The structure and absolute configurations of 3a and 4v were assigned by an X-ray crystallographic analysis of enantiopure samples
(see the Supporting Information for details). [e] The reaction was conducted at 40 oC, and then heated at 80 oC.
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10.1002/anie.201908284
Angewandte Chemie International Edition
COMMUNICATION
endo-3 with two quaternary stereocenters is formed (Table 2b).
However, we envisaged that the congested scaffold of lactone
endo-3 and the stabilization of C6-carbocation by substituent R4
might render the extrusion of CO2 both kinetically and
thermodynamically favored. This speculation was well
corroborated by density functional theory (DFT) calculations on
the energy profiles of the selected substrates (Table 3). As
expected, a lower energy barrier for the CO2 extrusion was
observed when the R4 group that could more effectively stabilize
the neighboring carbocation was introduced (R4 = H, 24.2
kcal/mol; R4 = Me, 20.0 kcal/mol; R4 = Ph, 15.4 kcal/mol). These
factors led the efficient one-step formation of diene 4 under mild
reaction conditions possible. However, in this scenario, Diels–
Alder reaction must undergo with high enantioselectivity and
diastereoselectivity simultaneously. Otherwise, if adduct exo-3 is
generated, it would give ent-4 in the following retro Diels–Alder
reaction, resulting in diminished ee of the final product. To our
delight, in the presence of Yb(OTf)3 (20 mol%) and (R)-L7 (24
mol%), the reaction of 1q with 2 afforded arene cis-dihydrodiol 4q
directly in 87% yield with > 99% ee. The excellent ee of 4q is
indicative of nearly perfect stereocontrol for the initial IEDDA
reaction (> 99% ee and > 99.5:0.5 d.r.).
activities.[19] To demonstrate the synthetic utility of this new
approach, we realized the expedient enantioselective synthesis of
their naturally occurring enantiomers from methyl benzoate ester
2,3-cis-dihydrodiol 4b, whose absolute configurations were
opposite to those obtained from enzymatic synthesis.[20] As shown
in Scheme 2, treatment of 4b (97% ee) with NMO and OsO4 (cat.)
afforded cis-diol 8 in 68% yield. The reduction of the ester group
of 8 was then subjected to DIBAL-H, followed by deprotection of
the acetal group under acidic conditions to provide (+)-MK7607
(6) in 81% yield. On the other hand, epoxidation of 4b (97% ee)
with mCPBA, followed by a stereoselective epoxide ring-opening
in refluxing tBuOH/phosphate buffer (pH = 8)[21] afforded anti-diol
9 in 32% yield over two steps. Then, the subsequent protection of
the diol 9 with TBSOTf, reduction of the ester with LiAlH4, and
global deprotection gave 1-epi-(+)-MK7607 7 in 71% yield.
OH
O
OMe
O
OMe
b) DIBAL-H
c) AcCl, MeOH
OH
OH
O
O
a) OsO4, NMO
68%
81%
2 steps
HO
O
O
HO
OH
OH
4b, 97% ee
8
6, (+)-MK7607
OH
O
OMe
O
OMe
Table 3. Calculated energy profiles of the CO2 extrusion process.a
d) mCPBA
e) tBuOH/phosphate
buffer (pH = 8)
f) TBSOTf
g) LiAlH4
h) HCl, MeOH
OH
OH
O
O
O
O
CO2Me
CO2Me
O
32%
2 steps
CO2Me
O
71%
3 steps
O
O
O
HO
HO
O
O
OH
7, 1-epi-(+)-MK7607
OH
4b, 97% ee
O
9
R4
O
R4
O
R4
3
endo-
TS
4
Scheme 2. Enantioselective total synthesis of (+)-MK7607 and 1-epi-(+)-
MK7607.
Entry, R4
endo-3
TS
4
1, R = H
0.0
0.0
0.0
24.2
20.0
15.4
−25.5
−25.9
−29.5
In conclusion, we have realized the first asymmetric catalytic
chemical synthesis of arene cis-dihydrodiols. This sequential
process consists of ytterbium-catalyzed asymmetric inverse-
electron-demand Diels–Alder reaction of 2-pyrone and retro
Diels–Alder extrusion of CO2. Utilizing this strategy, a wide range
of benzoate ester 2,3-cis-dihydrodiols bearing various
substituents were obtained efficiently with extremely high
2, R = Me
3, R = Ph
[a] Relative Gibbs free energies in dichloromethane (in kcal/mol) are reported.
Calculated at B3LYP/6-31G** level of theory.
Further exploration of the substrate scope revealed a wide
range of 6-substituted-2-pyrones (1r-1ag) that were compatible
with this cascade reaction (Table 2b). 2-Pyrones bearing 6-
substituted aryl groups including functionalized phenyl, 2-
naphthyl, and 2-thiophenyl led to the corresponding substituted
arene cis-dihydrodiols 4r-4y in good yields (35–88%) and > 99%
ee. Moreover, multisubstituted 6-aryl-3-carbomethoxyl-2-pyrones
were accommodated, providing highly enantioenriched
polysubstituted or polycyclic arene cis-dihydrodiols 4z-4ac
efficiently. 2-Pyrone bearing a 6-methyl group was tolerated, but
gave a low yield (4ad, 20% yield, 91% ee). The introduction of
aryl groups at the C4 or C5 position of 6-alkyl-2-pyrones further
improved the reactivities and enantioselective control of the
reaction (4ae-4ag, 71–88% yield, 96–99% ee). Interestingly, and
consistent with the above DFT calculations, substrates bearing a
C6 alkyl group (1ad-1ag) led to a mixture of lactone 3 and diene
enantioselectivities (up to
> 99% ee). Notably, when 6-
substituted-2-pyrones were employed as the substrates, the
corresponding arene cis-dihydrodiols were obtained efficiently in
a single step. This strategy provides a powerful chemical method
for the enantioselective synthesis of arene cis-dihydrodiols as a
reliable alternative to traditional enzymatic catalysis. Finally, the
synthetic utilities were demonstrated herein by efficient total
syntheses of bioactive (+)-MK7607 and 1-epi-(+)-MK7607.
Further applications of synthetic arene cis-dihydrodiols in more
complex natural product synthesis are under investigation in our
laboratory.
Acknowledgements
o
o
4 at 40 C, while further heating the reaction mixture at 80 C
afforded diene 4ae-4ag exclusively.
The National Natural Science Foundation of China (Grant No.
21801043) and Fudan University (start-up grant) are gratefully
acknowledged for financial support. We thank Dr. Derek Rhoades
Natural product (+)-MK7607 6 and its synthetic analog 1-epi-
(+)-MK7607 7 are carbasugars that exhibit important biological
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Keywords: arene cis-dihydrodiols • Diels–Alder Reaction • retro
Diels–Alder Reaction • asymmetric catalysis • total synthesis
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Xiao-Wei Liang†, Yunlong Zhao†, Xu-Ge
Si, Meng-Meng Xu, Jia-Hao Tan, Zhi-
Mao Zhang, Cheng-Gong Zheng, Chao
Zheng, and Quan Cai*
Page No. – Page No.
Enantioselective Synthesis of Arene
cis-Dihydrodiols from 2-Pyrones
Text for Table of Contents
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