Enantioselective Addition of Alkynyl Esters and Ethers to Aldehydes Catalyzed by a Cyclopropyl Amino Alcohol Based Zinc Catalyst

Article abstract of DOI:10.1055/s-0039-1690264

A novel and highly enantioselective synthesis of hydroxyalkynyl esters and ethers through the asymmetric addition of alkynyl esters or ethers to aldehydes promoted by a cyclopropyl amino alcohol based zinc catalyst has been developed. The method afforded a library of new enantioenriched hydroxyalkynol esters and ethers (up to 93percent yield; 95percent ee), and it was compatible with a broad range of functional groups. Moreover, it could be used in the synthesis of carbon-chain-elongated enantioenriched hydroxyalkynol esters and (2 R,5 R)-musclide-A1, a cardiotonic potentiating principle from musk.

Full text of DOI:10.1055/s-0039-1690264

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© Georg Thieme Verlag Stuttgart · New York
2019, 30, A–E
letter
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Y. Zhou et al.
Letter
Synlett
Enantioselective Addition of Alkynyl Esters and Ethers to Aldehydes
Catalyzed by a Cyclopropyl Amino Alcohol Based Zinc Catalyst
Yun Zhoua
Lifeng Wanga
Shuoning Lia
Sijie Maa
Patrick J. Walshb
Qinghua Biana
Fengqi Li*c
Ph
Ph
O
N
O
OH
OH
(Aryl) Alkyl
H
10 mol%
+
(Aryl) Alkyl
OR
n
3 equiv Me2Zn
toluene, 48 h
( )
OR
n
43 examples
up to 95% ee, 93% yield
( )
Min Wanga
Jiangchun Zhong*a
R = Ac, Bz, n-valeryl, i-butyryl, pivaloyl, phenylacetyl, Boc, Bn,
cyclopropylcarbonyl, cyclohexanoyl, TBDPS,TBS, t-Bu
a Department of Applied Chemistry, China Agricultural University, 2 West Yuanmingyuan Road,
Beijing 100193, P. R. of China
zhong@cau.edu.cn
b Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania,
231 South 34th Street, Philadelphia, PA 19104-6323, USA
c Institute of Plant and Environment Protection, Beijing Academy of Agriculture and Forestry
Sciences, No. 9 Shuguang Garden, Central Road, Beijing, 100097, P. R. of China
pandit@163.com
Received: 28.08.2019
Accepted after revision: 22.10.2019
Published online: 03.12.2019
Georges et al. prepared enantioenriched 4-hydroxyalk-2-
ynyl carbonates through the addition of alkyl prop-2-yn-1-
yl carbonates to aldehydes by using Carreira’s method.7
Princival and co-workers developed another successful ap-
proach to enantiopure propargylic acetates through an en-
zymatic kinetic resolution of racemic propargylic acetates
promoted by Candida antarctica lipase B.11
We have previously developed a cyclopropane-based
amino alcohol L1–zinc catalyst system that exhibited excel-
lent enantioselectivity in the addition of ethynylbenzene,
methyl propiolate, or 1,3-diynes to aldehydes.12 These re-
sults encouraged us to examine the use of our catalyst in
the challenging asymmetric synthesis of alkynol esters.
Here, we disclose an efficient and highly enantioselective
synthesis of hydroxyalkynol esters and ethers (up to 93%
yield, 95% ee) through the addition of alkynyl esters or
ethers to aromatic or aliphatic aldehydes in the presence of
the L1–zinc catalyst system. Furthermore, to demonstrate
the applicability of the method, we prepared (2R,5R)-mus-
clide-A1, a cardiotonic potentiating principle from musk,
together with several carbon-chain-elongated hydroxyalky-
nol esters.
DOI: 10.1055/s-0039-1690264; Art ID: st-2019-r0453-l
Abstract A novel and highly enantioselective synthesis of hydroxy-
alkynyl esters and ethers through the asymmetric addition of alkynyl
esters or ethers to aldehydes promoted by a cyclopropyl amino alcohol
based zinc catalyst has been developed. The method afforded a library
of new enantioenriched hydroxyalkynol esters and ethers (up to 93%
yield; 95% ee), and it was compatible with a broad range of functional
groups. Moreover, it could be used in the synthesis of carbon-chain-
elongated enantioenriched hydroxyalkynol esters and (2R,5R)-mus-
clide-A1, a cardiotonic potentiating principle from musk.
Key words zinc catalysis, hydroxyalkynyl esters, hydroxyalkynyl
ethers, alkynylation, musclide-A1, asymmetric catalysis
Chiral alkynol esters and ethers are versatile building
blocks for numerous natural products, drugs, and pesti-
cides, such as solandelactones,1 decarestrictine D,2 and con-
stanolactones A and B.3,4 Furthermore, these compounds, in
their enantioenriched forms, contain three functional
groups and can be transformed into optically active -hy-
droxy ,-unsaturated aldehydes,5 -aminooxy acids,6 1,2-
diols,7 or 1,4-, 1,5-, 1,6- or 1,7-diols, which are important
precursors for various bioactive organic compounds.8,9
However, only a few strategies for synthesizing chiral alkynol
esters and ethers have been reported. For examples, Carreira
and co-workers developed the first examples of enantiose-
lective and diastereoselective additions of aldehydes to
propargyl acetate (up to 95% yield and 97% ee) catalyzed by
stoichiometric (+)- or (–)-N-methylephedrine/Zn(OTf)2.5,10
We initially surveyed the effects of various reaction pa-
rameters on the enantioselective synthesis of (4S)-4-hy-
droxy-4-phenylbut-2-yn-1-yl acetate (3a) through the ad-
dition of propargyl acetate (2a) to benzaldehyde (1a) (Table
1). The optimized conditions required 3.0 equivalent of the
both propargyl acetate and Me2Zn with 1.0 equivalent of
benzaldehyde in toluene at 0 °C, catalyzed by 10 mol% of
the cyclopropane-based amino alcohol L1 (Table 1, entry
© 2019. Thieme. All rights reserved. Synlett 2019, 30, A–E
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
Y. Zhou et al.
Letter
Synlett
2).13 By comparison with the reported specific rotation,5
the absolute configuration of the addition product 3a was
assigned as S, which is consistent with the reaction mecha-
nism reported by Noyori and Trost and their respective co-
workers.14
with 90 and 85% ee, respectively. 2-Furaldehyde reacted
with propargyl benzoate (2h) to give product 3o in 60%
yield and 70% ee.
OH
10 mol% L1
3 equiv Me2Zn
O
Ar
ArCHO
+
O
toluene, 0 °C, 48 h
O
Table 1 Effect of Reaction Parameters on the Enantioselective Synthe-
sis of (4S)-4-Hydroxy-4-phenylbut-2-yn-1-yl acetate (3a)a
3
1
2a
O
OH
OH
Me OH
Me
OH
O
O
O
O
ligand, Me2Zn
O
O
O
O
O
+
3b, 89%, 94% ee
H
3a, 93%, 94% ee
3c, 90%, 92% ee
O
solvent, temp., 48 h
O
OMe OH
OH
OH
3a
O
2a
1a
MeO
Ph
Ph
O
O
Ph
Ph
OH
HO
N
H
Me
O
O
O
O
N
3f, 87%, 94% ee
3e, 88%, 93% ee
Ph
Ph
3d, 93%, 92% ee
O
N
OH
Br OH
OH
Me
OH
NH O
N
OH
O
O
O
O
O
O
MeO
O
L2
L1
L3
3h, 91%, 90% ee
3i, 85%, 91% ee
3g, 90%, 93% ee
OH
OH
OH
Entry
Ligand
(mol%)
2a/Me2Zn/ Solvent
Temp
(oC)
Yieldb
(%)
eec
(%)
O
1a
O
Cl
Br
NC
O
O
O
3k, 84%, 90% ee
3j, 87%, 92% ee
3l, 85%, 92% ee
1
2
–
3:3:1
3:3:1
3:3:1
3:3:1
3:3:1
3:3:1
3:3:1
3:3:1
3:3:1
3:3:1
3:3:1
3:3:1
2:2:1
4:4:1
toluene
0
35
93
94
49
59
90
72
86
95
53
73
96
75
94
0
OH
OH
OH
L1 (10)
L2 (10)
L3 (10)
L1 (10)
L1 (10)
L1 (10)
L1 (10)
L1 (10)
L1 (10)
L1 (5)
toluene
toluene
toluene
THF
0
0
94
–80
–54
91
O
O
Ph
3
O
O
O
O
4
0
O
3n, 82% , 85% ee
3m, 84%, 90% ee
3o, 60%, 70% ee
5
0
Scheme 1 Enantioselective synthesis of hydroxypropargylic esters 3a–
o through addition of propargyl esters to aromatic aldehydes. All reac-
tions were conducted on a 0.5 mmol scale. Isolated yields after chro-
matographic purification are reported, and ee values were determined
by chiral HPLC.
6
CH2Cl2
CHCl3
0
92
7
0
84
8
hexane
toluene
toluene
toluene
toluene
toluene
toluene
0
93
9
25
–20
0
88
10
11
12
13
14
93
In addition to propargyl acetate, other alkynylic esters
were also suitable substrates for the preparation of chiral
hydroxyalkynol esters and ethers 4b–p (Scheme 2).
Alkynylic esters with small alkyl groups (Me, Bu) or bulky
groups (t-Bu, i-Pr, c-Pr, Cy) gave the corresponding hy-
droxyalkynol esters 3a and 4b–f with uniformly excellent
enantioselectivities (88–93%) and in high yields (85–91%).
Furthermore, functional groups such as benzyl, which is
challenging because of its acidic -hydrogen atoms, and
carbonate, which readily binds to Lewis acidic metals, were
excellent substrates, and the addition products 4g and 4i
were generated in yields of 85 and 81% with 94 and 95% ee,
respectively. Interestingly, bulky alkynylic ester and acety-
lenic ethers also proved to be good substrates, affording the
corresponding products 4j–l and 4n in 81–92% ee and 71–
90% yield. Note that carbon-chain-elongated alkynylic es-
ters were also good substrates, generating the addition
products 4m, 4o, and 4p with slightly lower enantioselec-
tivities (73–84%); these carbon-chain-elongated alkynol es-
ter products could be converted into enantioenriched 1,5-,
1,6-, or 1,7-diols, which are key intermediates in the syn-
theses of many bioactive chemicals.8,9
88
L1 (20)
L1 (10)
L1 (10)
0
95
0
87
0
83
a All reactions were conducted on a 1.0 mmol scale.
b Isolated yield after chromatographic purification.
c Determined by chiral HPLC with a Daicel Chiralcel OD-H column.
After optimization, the method was extended to the re-
actions of other aromatic aldehydes. A series of hydroxy-
propargylic acetates 3a–o were obtained (Scheme 1). In
general, aromatic aldehydes containing electron-neutral,
electron-donating, or electron-withdrawing substituents in
the ortho-, meta-, and para-positions consistently gave high
yields of products 3a–n (82–93%) with excellent enantiose-
lectivities (85–94%). In particular, our alkynylation catalyst
was compatible with various functional groups, and afford-
ed hydroxypropargylic acetates bearing ether (3e–g), halide
(3i–k), cyano (3l), or hetaryl (3o) groups. Furthermore, 1-
naphthaldehyde and 2-naphthaldehyde gave the corre-
sponding products 3m and 3n in yields of 84 and 82% and
© 2019. Thieme. All rights reserved. Synlett 2019, 30, A–E

C
Y. Zhou et al.
Letter
Synlett
OH
OH
10 mol% L1
CHO
20 mol% L1
3 equiv Me2Zn
R
O
R'
3 equiv Me2Zn
OR
n
+
( )
OR
n
O
R'
O
RCHO
5
( )
+
toluene, 0 °C, 48 h
toluene, –20 °C, 48 h
1a
OH
2
4
O
O
O
2
6
OH
OH
OH
OH
OH
Bun
O
Pri
O
But
Bn
O
O
Ph
O
Ph
O
O
O
O
4b, 89%, 92% ee
4d, 85%, 88% ee
O
O
4c, 85%, 90% ee
6a, 66%, 85% ee
6c, 83%, 81% ee
6b, 53%, 80% ee
OH
OH
OH
OH
OH
OH
O
O
O
O
O
Ph
O
Ph
O
Ph
O
O
4g, 85%, 94% ee
4e, 91%, 90% ee
4f, 87%, 93% ee
O
O
O
6f, 62%, 93% ee
6d, 57%, 93% ee
6e, 49%, 87% ee
O
OH
OH
OH
OH
OH
OH
O
OBut
O
Ph
O
O
O
Ph
Ph
O
Ph
Ph
O
Ph
Ph
EtOOC
O
O
O
4i, 81%, 95% ee
O
4m, 76%, 84%ee
4h, 86%, 94% ee
6g, 87%, 86% ee
6i, 51%, 92% ee
6h, 51%, 95% ee
OH
OH
OH
OH
OH
OH
Ph
Ph
Ph
O
O
Ph
O
O
Ph
O
Si
O
Ph
O
O
4o, 87%, 80% ee
O
4l, 90%, 81% ee
4j, 71%, 92% ee
O
O
6j, 49%, 89% ee
6k, 46%, 91% ee
6l, 40%, 93% ee
OH
OH
OH
O
Scheme 3 Enantioselective synthesis of hydroxy propargylic esters
6a–l through addition of propargylic esters to aliphatic aldehydes. All
reactions were conducted on a 0.5 mmol scale. Isolated yields after
chromatographic purification are reported, and ee values were deter-
mined by chiral HPLC.
OBn
4k, 83%, 88% ee
OTBDPS
4n, 73%, 86% ee
O
Ph
4p, 78%, 73% ee
Scheme 2 Enantioselective synthesis of hydroxyalkynol esters and
ethers 4b–p through additions of alkynylic esters and ethers to benzal-
dehyde. All reactions were conducted on a 0.5 mmol scale. Isolated
yields after chromatographic purification are reported, and ee values
were determined by chiral HPLC.
selective addition of the alkynylzinc reagent prepared in
situ from ({[(1R)-1-methylprop-2-yn-1-yl]oxy}methyl)ben-
zene (2q) and diethylzinc to methacrylaldehyde (5f), cata-
lyzed by amino alcohol L1, gave the hydroxypropargylic
ether 6m (52% yield; dr = 16:1). The dr was determined by
1H NMR analysis of the methoxy region of the Mosher ester
derived from (2R)-3,3,3-trifluoro-2-methoxy-2-phenylpro-
panoyl chloride (Mosher’s acid chloride).16 Subsequent
PtO2-catalyzed hydrogenation and sulfonation with sulfur
trioxide–pyridine complex generated the sulfate 7 (66%
yield over two steps).17,18 Finally, debenzylation by Pd/C and
hydrogen gave (2R,5R)-musclide-A1 in 81% yield and
dr = 16:1 (based on an analysis of 1H NMR data).19 The spe-
cific rotation and NMR spectra of our synthetic musclide-
A1 matched the literature values.17
Our enantioselective synthesis of alkynol esters is not
limited to aromatic aldehydes, as aliphatic aldehydes also
successfully participated in the alkynylation reaction to
give the corresponding addition products 6a–l in good
yields and with excellent enantioselectivities (Scheme 3).
Aliphatic aldehydes bearing i-Pr, c-Pr, Cy, or tert-Bu groups
gave the corresponding alkynol esters 6a–d in 80–93% ee
and 53–83% yield. In an attempt to expand the scope of our
method further, we examined the enantioselective addition
of propargyl esters to ,-unsaturated aldehydes (6e–6l).
Methacrylaldehyde was a good substrate, giving the addi-
tion product 6f with 93% ee and 62% yield. Interestingly,
switching ethyl for methyl in the -position of the aldehyde
resulted in a dramatic increase in the yield from 62% for 6f
to 87% for 6g, but with a slight drop in the ee of the product
(93 to 86%). Methacrylaldehyde derivatives bearing ester or
phenyl groups in the -position gave addition products 6h
and 6i, respectively, with high levels of enantioselectivity
(92–95%). When a phenyl groups was introduced into the
-position of the enal, increasing the size of the group at
the -position resulted in a slight improvement in enanti-
oselectivity (89–93%; 6j–l).
OH
OBn
20 mol% L1, 3 equiv Me2Zn
O
+
(S)
6m
(R)
OBn
toluene, –20 °C, 48 h
52%, dr = 16:1
(R)
2q
5f
(1) PtO2, H2, MeOH, rt
OSO3H
OSO3H
Pd/C, H2
(2) sulfur trioxide–pyridine
OH
MeOH, rt
OBn
(R)
(R)
(R)
(R)
complex, THF, rt
66% in 2 steps
81%
7
(2R,5R)-musclide-A1
dr = 16:1
Scheme 4 Synthesis of (2R,5R)-musclide-A1
To demonstrate the utility of our alkynylation reaction,
we prepared (2R,5R)-musclide-A1 (Scheme 4). (2R,5R)-
Musclide-A1 was originally isolated from musk, a well-
known traditional Chinese medicine, and it has cardiotonic
potentiating activity.9a,c,15 The catalyst-controlled diastereo-
In summary, we have developed a simple and efficient
asymmetric synthesis of various new enantioenriched hy-
droxyalkynol esters and ethers (up to 93% yield, 95% ee)
through a highly enantioselective addition of alkynyl esters
© 2019. Thieme. All rights reserved. Synlett 2019, 30, A–E

D
Y. Zhou et al.
Letter
Synlett
and ethers to aromatic or aliphatic aldehydes by a zinc-cat-
alyzed reaction in the presence of a cyclopropane-based
amino alcohol ligand. The advantages of our method in-
clude high catalyst reactivity and enantioselectivity, mild
reaction conditions, the absence of additives, and a wide
substrate scope. Furthermore, the method was used to syn-
thesize carbon-chain-elongated enantioenriched alkynol
esters 4m, 4o, and 4p, as well as (2R,5R)-musclide-A1, a
cardiotonic potentiating principle from musk.
(12) (a) Zhong, J.-C.; Hou, S.-C.; Bian, Q.-H.; Yin, M.-M.; Na, R.-S.;
Zheng, B.; Li, Z.-Y.; Liu, S.-Z.; Wang, M. Chem. Eur. J. 2009, 15,
3069. (b) Zheng, B.; Li, S.-N.; Mao, J.-Y.; Wang, B.; Bian, Q.-H.;
Liu, S.-Z.; Zhong, J.-C.; Guo, H.-C.; Wang, M. Chem. Eur. J. 2012,
18, 9208.
(13) (4S)-4-Hydroxy-4-phenylbut-2-yn-1-yl Acetate (3a); Typical
Procedure
Prop-2-ynyl acetate (2a; 294.0 mg, 3.0 mmol, 3 equiv) was
added to a stirred solution of ligand L1 (35.1 mg, 0.1 mmol, 0.1
equiv) in anhyd toluene (0.5 mL) at rt under argon, and the
mixture was cooled to 0 °C. A 1.2 M solution of Me2Zn in
toluene (2.5 mL, 3.0 mmol, 3 equiv) was slowly added over 20
min, and the resulting mixture was warmed to rt (~0.5 h) and
then stirred for 1.5 h. The mixture was cooled to 0 °C and
PhCHO (1a; 106.1 mg, 1.0 mmol, 1 equiv) was added from a
syringe. The mixture was stirred for an additional 48 h at 0 °C
until the reaction was complete (TLC; silica gel, hexane–EtOAc,
7:1). The reaction was then quenched with H2O (5 mL) and the
mixture was diluted with Et2O (15 mL). The layers were sepa-
rated, and the aqueous phase was extracted with Et2O (3 × 20
mL). The combined organic layers were washed with brine (15
mL), dried (Na2SO4), filtered, and concentrated under reduced
pressure. The residue was purified by chromatography [silica
gel, hexane–EtOAc (7:1)] to give a colorless oil; yield: 189.9 mg
(93%, 94% ee); []D20 –2.0 (c 2.0, CHCl3) {Lit.5 []D25.8 +1.8 (c 0.51,
CHCl3) for 97% ee (R)-enantiomer}.
Funding Information
We are grateful to the National Key Technology Research and Devel-
opment Program of China for financial support (No.
2017YFD0201404).()
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1690264.
S
u
p
p
orit
n
gInformati
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n
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p
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orti
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o
n
References and Notes
HPLC (Daicel Chiralcel OD-H; 10% i-PrOH in hexane, 1.0
mL/min,  = 210 nm) tr (major): 13.79 min (S), tr (minor) = 18.29
min (R). 1H NMR (300 MHz, CDCl3):  = 7.54–7.50 (m, 2 H),
7.42–7.31 (m, 3 H), 5.51 (d, J = 6.0 Hz, 1 H), 4.76 (d, J = 1.8 Hz, 2
H), 2.39 (d, J = 6.1 Hz, 1 H), 2.10 (s, 3 H). 13C NMR (75 MHz,
CDCl3):  = 170.3, 140.1, 128.5, 128.4, 126.5, 86.4, 80.4, 64.3,
52.2, 20.6. HRMS (APCI-TOF): m/z [M + H]+ calcd for C12H13O3:
205.0865; found: 205.0874.
(1) (a) Robinson, A.; Aggarwal, V. K. Angew. Chem. Int. Ed. 2010, 49,
6673. (b) Yalla, R.; Raghavan, S. Org. Biomol. Chem. 2019, 17,
4572.
(2) (a) Radha Krishna, P.; Narasimha Reddy, P. V. Tetrahedron Lett.
2006, 47, 7473. (b) Kobayashi, Y.; Yoshida, S.; Asano, M.;
Takeuchi, A.; Acharya, H. P. J. Org. Chem. 2007, 72, 1707.
(c) Gupta, K. P.; Kumar, P. Eur. J. Org. Chem. 2008, 1195; corri-
gendum: Eur. J. Org. Chem. 2008, 1993.
(3) (a) Yu, J.; Lai, J.-Y.; Ye, J.; Balu, N.; Reddy, L. M.; Duan, W.; Fogel,
E. R.; Capdevila, J. H.; Falck, J. R. Tetrahedron Lett. 2002, 43, 3939.
(b) Pietruszka, J.; Wilhelm, T. Synlett 2003, 1698.
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(6) Chang, X.-W.; Zhang, D.-W.; Chen, F.; Dong, Z.-M.; Yang, D.
Synlett 2009, 3159.
(7) Georges, Y.; Allenbach, Y.; Ariza, X.; Campagne, J.-M.; Garcia, J.
J. Org. Chem. 2004, 69, 7387.
(8) (a) Adger, B. M.; Carreira, E. M. WO 2002094741, 2002. (b) Sans
Diez, R.; Adger, B.; Carreira, E. M. Tetrahedron 2002, 58, 8341.
(c) Princival, I. M. R. G.; Ferreira, J. G.; Silva, T. G.; Aguiar, J. S.;
Princival, J. L. Bioorg. Med. Chem. Lett. 2016, 26, 2839.
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(9) (a) Kadota, S.; Orito, T.; Kikuchi, T.; Uwano, T.; Kimura, I.;
Kimura, M. Tetrahedron Lett. 1991, 32, 1733. (b) Amador, M.;
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(c) Ortiz, J.; Ariza, X.; Garcia, J. Tetrahedron: Asymmetry 2003,
14, 1127.
(4S)-4-Hydroxy-4-phenylbut-2-yn-1-yl Cyclohexanecarbox-
ylate (4f)
Colorless oil; yield: 236.9 mg (87%; 93% ee); []D20 +10.0 (c 1.3,
CHCl3). HPLC (Daicel Chiralpak AD-H; 10% i-PrOH–hexane, 1.0
mL/min,
 = 210 nm): tr (major): 10.06 min (S); tr
(minor): 11.14 min (R). 1H NMR (300 MHz, CDCl3):  = 7.52 (dd,
J = 7.9, 1.5 Hz, 2 H), 7.41–7.32 (m, 3 H), 5.50 (d, J = 6.1 Hz, 1 H),
4.75 (d, J = 1.8 Hz, 2 H), 2.44 (d, J = 6.2 Hz, 1 H), 2.39–2.29 (m, 1
H), 1.93–1.89 (m, 2 H), 1.77–1.63 (m, 3 H), 1.51–1.39 (m, 2 H),
1.35–1.15 (m, 3 H). 13C NMR (75 MHz, CDCl3):  = 175.3, 140.1,
128.6, 128.5, 126.6, 86.2, 81.0, 64.5, 52.0, 42.9, 28.9, 25.7, 25.3.
HRMS (APCI-TOF): m/z [M + H]+ calcd for C17H21O3: 273.1491;
found: 273.1495.
(4S,5E)-7-Ethoxy-4-hydroxy-5-methyl-7-oxohept-5-en-2-yn-
1-yl Benzoate (6h)
Colorless oil; yield: 154.0 mg (51%, 95% ee); []D21 –8.0 (c 2.5,
CHCl3). HPLC (Daicel Chiralcel OD-H; 5% i-PrOH–hexane, 1.0
mL/min,  = 220 nm): tr (major): 11.34 min (S); tr (minor): 11.93
min (R). 1H NMR (300 MHz, CDCl3):  = 8.02 (dd, J = 5.2, 3.3 Hz,
2 H), 7.59–7.53 (m, 1 H), 7.42 (dd, J = 10.5, 4.7 Hz, 2 H), 6.09–
6.08 (m, 1 H), 4.93 (d, J = 1.7 Hz, 2 H), 4.86 (s, 1 H), 4.15 (q,
J = 7.1 Hz, 2 H), 3.26 (br s, 1 H), 2.21 (d, J = 1.2 Hz, 3 H), 1.25 (t,
J = 7.1 Hz, 3 H). 13C NMR (75 MHz, CDCl3):  = 166.6, 165.9,
154.5, 133.3, 129.8, 129.2, 128.4, 116.4, 84.7, 80.4, 66.5, 60.0,
52.6, 15.0, 14.1. HRMS (APCI-TOF): m/z [M – OH]+ calcd for
(10) Ham, P.; Deng, J.; Selvakumar, S.; Sibi, M. P. In e-EROS Encyclope-
dia of Reagents for Organic Synthesis; Wiley: Chichester, 2011, ;
DOI: 10.1002/047084289X.rz023.pub2.
(11) Ferreira, J. G.; Princival, C. R.; Oliveira, D. M.; Nascimento, R. X.;
Princival, J. L. Org. Biomol. Chem. 2015, 13, 6458.
C
17H17O4: 285.1127; found: 285.1125.
© 2019. Thieme. All rights reserved. Synlett 2019, 30, A–E

E
Y. Zhou et al.
Letter
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