Rhodium-catalyzed enantioselective 1,2-addition of arylboronic acids to heteroaryl α-ketoesters for synthesis of heteroaromatic α-hydroxy esters

Article abstract of DOI:10.1039/c2ob26316e

The first example of catalytic asymmetric 1,2-addition of arylboronic acids to heteroaryl α-ketoesters has been developed for the highly efficient and enantioselective synthesis of quaternary carbon-containing heteroaromatic α-hydroxy esters. The reaction works well with a variety of α-ketoesters including 3-indoleglyoxylates, 3-benzofuranglyoxylates and 3-benzothiopheneglyoxylates under very mild conditions, affording the corresponding products in moderate to good yields with high enantiomeric excesses (up to 97%).

Full text of DOI:10.1039/c2ob26316e

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ARTICLE TYPE
Rhodium-catalyzed enantioselective 1,2-addition of arylboronic acids to
heteroaryl α-ketoesters for synthesis of heteroaromatic α-hydroxy esters
Hui Wang, Ting-Shun Zhu and Ming-Hua Xu*
Received (in XXX, XXX) Xth XXXXXXXXX 200X, Accepted Xth XXXXXXXXX 200X
5
DOI: 10.1039/b000000x
The first example of catalytic asymmetric 1,2-addition of arylboronic acids to heteroaryl α-ketoesters has
been developed for highly efficient and enantioselective synthesis of quaternary carbon-containing
heteroaromatic α-hydroxy esters. The reaction works well with a variety of α-ketoesters including 3-
indoleglyoxylates, 3- benzofuranglyoxylates and 3-benzothiopheneglyoxylates under very mild
10 conditions, affording the corresponding products in moderate to good yields with high enantiomeric
excesses (up to 97%).
45
today a general method to directly access highly optically active
heteroaromatic α-hydroxy carbonyl compounds is not available.
Introduction
Heteroaromatic moieties are commonly found in many
pharmaceutical compounds and natural products.1 Among them,
15 N-heterocycles such as indoles constitute a particularly intriguing
class of compounds with diverse biological activities.2 On the
other hand, optical active α-hydroxy carbonyl compounds are
very important structural motifs in numerous biologically
interesting compounds.3 Consequently, development of efficient
20 synthetic methods to access enantiomerically enriched
heteroaromatic α-hydroxy carbonyl compounds is of great
interest to organic and medicinal chemists.4-6 Despite
considerable advances, however, asymmetric Friedel-Crafts
reaction of electron rich indoles with α-ketoesters or its analogues
25 is the only used methodology for the direct synthesis of chiral 3-
indolyl α-hydroxy esters (Scheme 1). While the Friedel-Crafts
approach provides straightforward access to the corresponding
indole derivatives, one inevitable drawback is that the feasibility
of the reaction and selectivity of the product largely rely on the
30 electronic nature of the substrates. Although some efficient chiral
catalysts have been developed, they are mostly limited to highly
electrophilic substrate 3,3,3-trifluoropyruvate.5 To the best of our
knowledge, there is only one example of bifunctional cinchona
alkaloid catalyst, reported by Deng, was applicable toward aryl α-
35 ketoesters, but the scope is still limited.6 Fairly speaking, until
OR
B(OH)2
O
O
R1
b
[M]/L*
X
R1
HO COOR
X = NP, O, S
R2
a
b
c
1,2-addition
*
α
to -ketoesters
R2
OR
O
X
O
c
B(OH)2
R2
R1
Friedel-Crafts of indoles
(known approach)
[M]/L*
X
X = NP, O, S
Scheme 1 Synthetic strategies to heteroaryl α-hydroxy esters
50
To address these issues, we conceived an alternative
methodology using transition metal-catalyzed asymmetric
arylation strategy7 (Scheme 1). The transition-metal-catalyzed
asymmetric nucleophilic addition of organometallic reagents to α-
55 keto carbonyl compounds is an attractive method for the efficient
synthesis of enantioenriched α-hydroxy carbonyl compounds.8
Especially, the use of stable and commercially available
arylboronic acids in place of common organometallic reagents
has attracted considerable attention.9,10 Surprisingly, despite
60 recent progress, no examples of 1,2-addtion for heteroaromatic α-
hydroxy carbonyl compounds synthesis were documented. Herein,
we describe our successful development of this arylation
approach as a new promising method for the preparation of
highly optically active heteroaromatic α-hydroxy esters under
65 extremely mild conditions.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555
Zuchongzhi Road, Shanghai 201203, People’s Republic of China. E-mail:
40 xumh@mail.shcnc.ac.cn; Fax: +86 21 5080 7388; Tel: +86 21 5080
7388
† Electronic Supplementary Information (ESI) available: experimental
details including copies of 1H and 13C NMR and HPLC spectra. See
DOI: 10.1039/b000000x/
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Organic & Biomolecular Chemistry
Page 2 of 8
further efforts to improve the yield were unsuccessful (entries 12-
Results and discussion
14). Finally, taking account of both factors—reaction yield and
enantioselectivity, easily accessible ethyl ester was utilized for
further studies.
Our laboratory recently reported the design of a new family of
chiral sulfur-olefin ligands and their successful application in the
Rh-catalyzed asymmetric reactions.11,12 Simple chiral cinnamyl
sulfinamide 1 was found to be an elegant ligand in 1,2-addition of
arylboronic acids to α-ketoesters and α-diketones, and gave a
broad range of aryl α-hydroxy esters with very high
enantioselectivities (up to 95% ee).11d Inspired by this success,
we wondered that the preparation of enantioenriched
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55 With the optimized conditions established, we then decided to
investigate the scope of this reaction. A series of structurally
differential arylboronic acids were reacted with ethyl 3-
indolylglyoxylates 5c, 5h-o. In most cases, the reactions went to
completion smoothly in 12 hours and gave excellent
60 enantioselectivities, displaying a wide range of substrate scope.
As shown in Table 2, arylboronic acids bearing different
substituents at para- and meta-positions can be all employed
successfully as the adducts to afford the desired products in
moderate to good yields with excellent enantioselectivities
65 (entries 1-11). The electronic properties of the arylboronic acids
did not appear to affect the selectivity of the reaction. In addition
to simple 5c, 3-indolylglyoxylates 5i–n with either electron-
donating or electron-withdrawing groups (R3) on the indole
benzene ring are mostly found to be suitable substrates, they
70 exhibited equally high reactivity and led to the formation of
highly optically active 3-indolyl α-hydroxy esters in moderate to
good yields (entries 13–18). However, substituent at 4-position
led to severe disadvantages on reaction stereocontrol probably
due to steric replusion, in the case of substrate 5h, a large
75 decrease in enantioselectivity was observed (40% ee, entry 12).
Notably, sterically encumbered substrate 5o with methyl
substituent at 2-position of pyrrole ring could also be applied in
the transformation (entry 19). The absolute configuration of the
newly formed quaternary carbon center was considered as (R) by
80 analogy of our former observations.11d
5
10 heteroaromatic α-hydroxy esters might be achieved with the same
chiral sulfur-olefin catalysis protocol.
We began our studies by evaluating the reaction between α-
ketoester 2a and boronic acids 3a and 3b using chiral cinnamyl
sulfinamide 1 as ligand and [Rh(COE)2Cl]2 as catalyst (Scheme
15 2). In contrast to the excellent results in the previous studies, the
combination of aryl α-ketoester and heteroaryl boronic acid
appeared to be not very successful, affording the desired products
in only 36% and 15% yields and moderate enantioselectivities.
O
[Rh(COE)2Cl]2/1
KOH (0.1 M)/THF, rt
OEt
+
COOEt
HO
*
O
O
S
MeO
B(OH)2
X
2a
OMe
Ph
N
1
H
4a
: 36% yield, 57% ee
X
4b
: 15% yield, 88% ee
3a
: X = NBoc
3b
: X = S
20
Scheme 2 1,2-Addition of heteroaryl boronic acids to aryl α-ketoester
As an alternative access, the combination of heteroaryl α-
ketoester and aryl boronic acid was subsequently considered.
Fortunately, the corresponding heteroaryl α-ketoesters such as 3-
Table 1 Optimization of the Reaction Conditions.a
OR1
25 indolylglyoxylates and 3-benzothiopheneylglyoxylates can be
easily prepared in high yields via Friedel-Crafts reaction of indole
or benzothiophene with oxalyl chloride, followed by
esterification in one pot.13 We first examined the potential of
reaction between methyl 3-indolylglyoxylate and p-anisylboronic
30 acid (Table 1, entry 1). To our disappointment, most of the 3-
indolylglyoxylate 5a remained and no product was detected.
Same result was observed with the corresponding N-methyl 3-
indolylglyoxylate. To avoid possible coordination interference of
indole nitrogen to the rhodium catalytic system and also further
35 enhance the electrophilicity of the indolyl α-ketoesters, we chose
N-Boc protected 3-indolylglyoxylate 5b as substrate. As excepted,
the reaction between 5b and p-anisylboronic acid underwent
smoothly and afforded the desired tertiary 3-indolyl α-hydroxy
ester 7b in moderate yield (61%) and with excellent
40 enantioselectivity (95% ee, entry 2). Notably, the use of even
milder conditions employing less amounts of base could lead to
the formation of 7b in very good yield (92%) without the loss of
enantioselectivity (95% ee, entry 5). Varying the ester substituent
from methyl to ethyl, isopropyl, tert-butyl, or benzyl did not seem
45 to affect the enantioselectivity of the reaction (entries 7–10). With
ethyl ester 5c, the best yield of 94% was obtained (entry 7). When
phenyl ester was employed, product 7g was obtained with slightly
better enantioselectivity (98% ee), but a large decrease in yield
(50%) was also observed due to competitive hydrolysis of the
50 aromatic ester substrate (entry 11). In this phenyl ester case,
O
B(OH)2
COOR1
HO
O
[Rh(COE)2Cl]2/1
*
+
KOH (aq.), THF, rt
N
R2
N
OMe
R2
OMe
5
6a
7
Yield
(%)b
ee
Entry
R1
R2
KOH
7
(%)c
-
1
2
Me (5a)
Me (5b)
Me (5b)
Me (5b)
Me (5b)
Me (5b)
Et (5c)
iPr (5d)
tBu (5e)
Bn (5f)
Ph (5g)
H
1.5 M, 0.5 equiv
1.5 M, 0.5 equiv
0.5 M, 0.5 equiv
0.1 M, 0.2 equiv
0.1 M, 0.1 equiv
0.01 M, 0.1 equiv
0.1 M, 0.1 equiv
0.1 M, 0.1 equiv
0.1 M, 0.1 equiv
0.1 M, 0.1 equiv
0.1 M, 0.1 equiv
-
7a
7b
7b
7b
7b
7b
7c
7d
7e
7f
Boc
Boc
Boc
Boc
Boc
Boc
Boc
Boc
Boc
Boc
61
76
91
92
78
94
89
65
90
50
95
95
95
95
94
95
95
96
95
98
3
4
5
6
7
8
9
10
11
7g
a
Reactions were carried out with α-ketoester 5 (0.25 mmol) and p-
anisylboronic acid 6a (1.5 equiv, 0.375 mmol) in the presence of 3 mol%
85 of [Rh], 3.3 mol% of ligand 1, and aqueous KOH in 1.0 mL of THF at rt
b
d
for 12 h. Isolated yield. c Determined by Chiral HPLC analysis. The
reaction was carried out at 60 °C.
2
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Page 3 of 8
Organic & Biomolecular Chemistry
Conclusion
Table
2 Asymmetric 1,2-Addition of Arylboronic Acids to 3-
Indolylglyoxylates 5 Catalyzed by [Rh(COE)2Cl]2/1.a
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a highly efficient and
In summary, we have developed
25 enantioselective route to quaternary carbon-containing
heteroaromatic α-hydroxy esters through a catalytic asymmetric
1,2-addition approach. The structurally extremely simple chiral
cinnamyl sulfinamide 1 is an elegant ligand for rhodium-
catalyzed asymmetric arylation of arylboronic acids with
30 heteroaromatic glyoxylates. The reaction works well with a
variety of α-ketoesters including 3-indoleglyoxylates, 3-
benzofuranglyoxylates and 3-benzothiopheneglyoxylates under
very mild conditions, affording the corresponding products in
moderate to good yields with high enantiomeric excesses (up to
35 97%). To our knowledge, this is the first example of catalytic
asymmetric 1,2-addition of arylboronic acids to heteroaryl α-
ketoesters. It provides a new asymmetric approach to the
synthesis of heteroaromatic α-hydroxy carbonyl compounds. In
comparison of the known asymmetric Friedel-Crafts reaction of
40 indoles with aryl α-ketoesters, the current method shows no
dependence on the electronic nature of the substrates, and gives a
more promising result. We expect this methodology will be
useful and find wide applications in organic synthesis and
medicinal chemistry.
OEt
R3
O
ArB(OH)2
O
COOEt
Ar
HO
1
[Rh(COE)2Cl]2/
R3
KOH (0.1 M)/THF, rt
N
N
Boc
Boc
5
7
5
Yield
ee
Entry
R3
Ar
7
(%)b
94
(%)c
1
2
H (5c)
H (5c)
4-MeO-C6H4
4-Me-C6H4
Ph
95
95
97
96
96
95
96
95
95
94
93
40
95
95
93
96
97
96
95
7c
7h
7i
87
80
85
84
78
80
70
74
78
81
68
79
75
88
84
92
88
73
3
H (5c)
4
H (5c)
4-Cl-C6H4
7j
5
H (5c)
4-F-C6H4
7k
7l
6
H (5c)
3-Me-C6H4
3-MeO-C6H4
3-Cl-C6H4
7
H (5c)
7m
7n
7o
7p
7q
7r
7s
8
H (5c)
9
H (5c)
3-F-C6H4
10
11
12
13
14
15
16
17
18
19
H (5c)
1-naphthyl
2-naphthyl
4-MeO-C6H4
4-MeO-C6H4
4-MeO-C6H4
4-MeO-C6H4
4-MeO-C6H4
4-MeO-C6H4
4-MeO-C6H4
4-MeO-C6H4
H (5c)
45
4-Me (5h)
5-Me (5i)
5-OMe (5j)
5-Br (5k)
6-Me (5l)
6-Br (5m)
7-Me (5n)
2-Me (5o)
Experimental
7t
General procedure for the synthesis of 5b-f, 5h-o. Oxalyl
chloride (1.40 g, 11 mmol) was added dropwise to a solution of
indole (10 mmol) in THF (50 mL) at 0 °C. After the reaction was
50 complete (monitored by TLC). Alcohol (5 mL) was added and
stirred for 0.5 h. The resulting suspension was filtered and the
filter cake was washed with cold ether. The filter cake was dried
under vacuum to give the ketoesters as a yellow solid, which was
used without further purification. A suspension of the above solid
55 in CH2Cl2 (30 mL) was treated with Boc2O (3.27g, 15 mmol) and
catalytic amount of DMAP at rt for 3 h to give the crude product.
The residue was purified by silica gel column chromatography to
afford the desired 3-indolylglyoxylates 5.
7u
7v
7w
7x
7y
a
Reactions were carried out with α-ketoester 5 (0.25 mmol) and
arylboronic acid 6 (1.5 equiv, 0.375 mmol) in the presence of 3 mol% of
[Rh], 3.3 mol% of ligand 1, and KOH (0.1 M, 0.1 equiv) in THF (1.0 mL)
at rt for 12 h. b Isolated yield. c Determined by Chiral HPLC analysis.
10
1
To further extend the reaction scope, asymmetric arylation of α-
Compound 5d. Yellow solid, 2.85 g, 86% yield. H NMR (300
(3-benzofuran)-ketoesters
ketoesters 5q with arylboronic acid catalyzed by the rhodium
complex of sulfinamide 1 were carried out. Gratifyingly, the
15 expected products were obtained in good yields with excellent ee
values (95%-97%, Scheme 3). Such products are hardly obtained
via the Friedel-Crafts approach due to the low electronic density
of the benzofuran and benzothiophene ring.14
5p
and
α-(3-benzothiophene)-
60 MHz, CDCl3): δ 1.44 (d, J = 6.3 Hz, 6H), 1.71 (s, 9H), 5.25-5.33
(m, 1H), 7.39-7.42 (m, 2H), 8.16-8.18 (m, 1H), 8.39-8.41 (m, 1H),
8.76 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 21.7, 28.0, 70.6,
85.8, 115.0, 116.3, 122.5, 124.8, 126.0, 127.5, 135.3, 136.9,
148.7, 161.6, 179.6; MS m/z (ESI, relative intensity) 354
65 ([M+Na]+, 44), 276 (100), 234 (70), 188 (29); HRMS (ESI-FT)
for C18H21NO5 [M +Na]+: calcd 354.1312, found 354.1313.
1
OEt
O
Compound 5e. Yellow solid, 2.83 g, 82% yield. H NMR (300
COOEt
Ar
HO
MHz, CDCl3): δ 1.64 (s, 9H), 1.71 (s, 9H), 7.38-7.41 (m, 2H),
8.14-8.17 (m, 1H), 8.37-8.40 (m, 1H), 8.70 (s, 1H); 13C NMR
70 (100 MHz, CDCl3): δ 27.96, 28.03, 84.1, 85.7, 115.0, 116.3,
122.6, 124.8, 125.9, 127.6, 135.3, 136.6, 148.7, 161.4, 180.5; MS
m/z (ESI, relative intensity) 368 ([M+Na]+, 70), 234 (62), 188
(100); HRMS (ESI-FT) for C19H23NO5 [M +Na]+: calcd 368.1468,
found 368.1458.
O
[Rh(COE)2Cl]2/1
+
ArB(OH)2
KOH (0.1 M)/THF, rt
X
X
5p
: X=O
5p: X=O
5q
: X=S
Ar = 4-MeO-C6H4
Ar = 4-Cl-C6H4
Ar = 4-MeO-C6H4
8a: 95% yield, 95% ee
8b
: 75% yield, 95% ee
9: 83% yield, 97% ee
20
Scheme 3 1,2-Addition of arylboronic acids to other heteroaryl α-
ketoesters
1
75 Compound 5f. White solid, 3.33 g, 88% yield. H NMR (300
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 3

Organic & Biomolecular Chemistry
Page 4 of 8
MHz, CDCl3): δ 1.69 (s, 9H), 5.40 (s, 2H), 7.36-7.42 (m, 5H),
CDCl3): δ 8.9, 22.8, 57.4, 81.3, 110.8, 113.2, 114.7, 118.5, 121.1,
7.47-7.49 (m, 2H), 8.15-8.18 (m, 1H), 8.37-8.40 (m, 1H), 8.74 (s,
1H); 13C NMR (100 MHz, CDCl3): δ 28.1, 67.9, 85.9, 115.1,
116.3, 122.6, 124.9, 126.1, 127.4, 128.6, 128.8, 134.7, 135.4,
123.0, 130.7, 131.9, 143.1, 156.4, 173.7; MS m/z (ESI, relative
intensity) 420 ([M+Na+2]+, 99), 418([M+Na]+, 100), 340 (64),
266 (41); HRMS (ESI-FT) for C17H18BrNO5 [M +Na]+: calcd
View Online
5
137.1, 148.7, 161.8, 178.8; MS m/z (ESI, relative intensity) 402 60 418.0261, found: 418.0257.
([M+Na]+, 100), 324 (70), 129 (42); HRMS (ESI-FT) for
1
Compound 5n. White solid, 2.52 g, 76% yield. H NMR (300
MHz, CDCl3): δ 1.45 (t, J = 5.4 Hz, 3H), 1.68 (s, 9H), 2.60 (s,
3H), 4.43 (q, J = 7.5 Hz, 2H), 7.20 (d, J = 5.7 Hz, 1H), 7.31 (t, J
= 5.7 Hz, 1H) ,8.29 (d, J = 6.0 Hz, 1H), 8.72 (s, 1H); 13C NMR
C22H21NO5 [M +Na]+: calcd 402.1312, found 402.1300.
1
Compound 5h. White solid, 2.38 g, 72% yield. H NMR (300
MHz, CDCl3): δ 1.44 (t, J = 7.2 Hz, 3H), 1.69 (s, 9H), 2.77 (s,
10 3H), 4.43 (q, J = 6.9 Hz, 2H), 7.14 (d, J = 7.5 Hz, 1H), 7.26-7.32 65 (100 MHz, CDCl3): δ 14.0, 15.5, 28.2, 62.4, 86.0, 114.9, 115.1,
(m, 1H), 8.05 (d, J = 8.1 Hz, 1H), 8.57 (s, 1H); 13C NMR (100
MHz, CDCl3): δ 14.1, 22.8, 28.0, 62.4, 85.8, 112.6, 117.9, 125.8,
126.1, 126.9, 133.4, 136.4, 137.8, 148.4, 163.5, 179.7; MS m/z
(ESI, relative intensity) 354 ([M+Na]+, 42), 276 (100), 202 (53);
15 HRMS (ESI-FT) for C18H21NO5 [M +Na]+: calcd 354.1312,
found: 354.1319.
120.3, 124.4, 124.9, 126.5, 135.6, 147.4, 149.6, 165.1, 183.8; MS
m/z (ESI, relative intensity) 354 ([M+Na]+, 43), 276 (100), 202
(38); HRMS (ESI-FT) for C18H21NO5 [M +Na]+: calcd 354.1312,
found: 354.1322.
1
70 Compound 5o. White solid, 2.22 g, 67% yield. H NMR (300
MHz, CDCl3): δ 1.42 (t, J = 5.4 Hz, 3H), 1.71 (s, 9H), 2.83 (s,
3H), 4.45 (q, J = 5.4 Hz, 2H), 7.31-7.33 (m, 1H), 7.94-7.96 (m,
1H), 8.04-8.06 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 8.9, 16.7,
22.7, 57.2, 80.5, 110.7, 115.0, 119.8, 120.0, 123.4, 124.1, 129.5,
1
Compound 5i. White solid, 2.98 g, 90% yield. H NMR (300
MHz, CDCl3): δ 1.44 (t, J = 7.2 Hz, 3H), 1.70 (s, 9H), 2.48 (s,
3H), 4.43 (q, J = 7.5 Hz, 2H), 7.22 (d, J = 8.1 Hz, 1H), 8.02 (d, J
20 = 8.4 Hz, 1H), 8.19 (s, 1H), 8.72 (s, 1H); 13C NMR (100 MHz, 75 134.13, 143.3, 156.9, 173.6; MS m/z (ESI, relative intensity) 354
CDCl3): δ 8.9, 16.3, 22.9, 57.2, 80.5, 109.5, 110.8, 117.2, 122.2,
122.4, 128.3, 129.5, 131.9, 143.5, 156.9, 174.1; MS m/z (ESI,
relative intensity) 354 ([M+Na]+, 44), 276 (100), 202 (38);
HRMS (ESI-FT) for C18H21NO5 [M +Na]+: calcd 354.1312,
25 found: 354.1314.
([M+Na]+, 54), 276 (100), 232 (31), 202 (40); HRMS (ESI-FT)
for C18H21NO5 [M +Na]+: calcd 354.1312, found: 354.1318.
Compound 5g. Phenyl chlorooxoacetate (12 mmol) was added to
a solution of indole (10 mmol) in THF (50 mL) at 0 °C. The
80 mixture was then warmed up to rt and stirred overnight. The
resulting suspension was filtered and the filter cake was washed
with cold ether. The filter cake was dried under vacuum to give
the ketoesters as a yellow solid, which was used without further
purification. A suspension of the above solid in CH2Cl2 (30 mL)
1
Compound 5j. White solid, 3.09 g, 89% yield. H NMR (300
MHz, CDCl3): δ 1.44 (t, J = 7.5 Hz, 3H), 1.69 (s, 9H), 4.42 (q, J
= 7.2 Hz, 2H), 7.47-7.50 (m, 1H), 8.02 (d, J = 6.6 Hz, 1H), 8.52
(s, 1H), 8.76 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 8.9, 22.9,
30 50.5, 57.2, 80.6, 99.1, 110.2, 110.7, 110.8, 123.3, 124.6, 132.0, 85 was treated with Boc2O (3.27g, 15 mmol) and catalytic amount of
143.5, 152.3, 156.8, 174.1; MS m/z (ESI, relative intensity) 370
([M+Na]+, 44), 292 (100), 218 (19); HRMS (ESI-FT) for
C18H21NO6 [M +Na]+: calcd 370.1261, found: 370.1260.
DMAP at rt for 3 h to give the crude product. The residue was
purified by silica gel column chromatography to afford 5g as a
1
white solid 2.92 g, 80% yield. H NMR (300 MHz, CDCl3): δ
1.70 (s, 9H), 7.27 (d, J = 8.1 Hz, 2H), 7.31 (d, J = 10.5 Hz, 2H),
90 7.42-7.50 (m, 4H), 8.19-8.22 (m, 1H), 8.44-8.47 (m, 1H), 8.87 (s,
1H); 13C NMR (100 MHz, CDCl3): δ 28.0, 86.0, 115.1, 116.1,
121.2, 122.5, 125.0, 126.1, 126.6, 127.4, 129.7, 135.3, 137.2,
148.5, 150.2, 160.1, 177.7; MS m/z (ESI, relative intensity) 388
([M+Na]+, 33), 310 (90), 188 (100); HRMS (ESI-FT) for
95 C21H19NO5 [M +Na]+: calcd 388.1155, found 388.1170.
1
Compound 5k. White solid, 3.32 g, 84% yield. H NMR (300
35 MHz, CDCl3): δ 1.43 (t, J = 5.4 Hz, 3H), 1.69 (s, 9H), 3.89 (s,
3H), 4.43 (q, J = 7.2 Hz, 2H), 6.98-7.02 (m, 1H), 7.89 (s, 1H),
8.03 (d, J =9.3 Hz, 1H), 8.74 (s, 1H); 13C NMR (100 MHz,
CDCl3): δ 14.1, 28.0, 62.6, 86.4, 115.4, 116.5, 118.6, 125.2,
129.0, 134.0, 137.5, 148.3, 161.6, 178.7; MS m/z (ESI, relative
40 intensity) 420 ([M+Na+2]+, 99), 418([M+Na]+, 100), 340 (70),
266 (48); HRMS (ESI-FT) for C17H18BrNO5 [M +Na]+: calcd
418.0261, found: 418.0254.
Compound 5p was synthesized following the literature
1
procedure.15 Yellow oil 1.24 g, 92% yield. H NMR (300 MHz,
CDCl3): δ 1.45 (t, J = 5.1 Hz, 3H), 4.44 (q, J = 5.4 Hz, 2H), 7.38-
7.44 (m, 2H), 7.54-7.58 (m, 1H), 8.26-8.30 (m, 1H), 8.90 (s, 1H);
100 13C NMR (100 MHz, CDCl3): δ 14.1, 62.8, 111.6, 118.7, 122.8,
124.2, 125.1, 126.2, 155.1, 156.0, 161.1, 178.4;
1
Compound 5l. White solid, 2.85 g, 86% yield. H NMR (300
MHz, CDCl3): δ 1.44 (t, J = 7.2 Hz, 3H), 1.70 (s, 9H), 2.49 (s,
45 3H), 4.43 (q, J = 7.5 Hz, 2H), 7.21 (d, J = 8.7 Hz, 1H), 8.01 (s,
1H), 8.24 (d, J = 8.1 Hz, 1H), 8.70 (s, 1H); 13C NMR (100 MHz,
CDCl3): δ 8.9, 16.9, 22.8, 57.2, 80.5, 110.1, 111.1, 116.9, 119.9,
121.1, 130.6, 131.1, 131.4, 143.6, 156.8, 174.0; MS m/z (ESI,
relative intensity) 354 ([M+Na]+, 48), 276 (100), 202 (58);
Compound 5q was synthesized following the literature
1
procedure.16 Brown oil 1.99 g, 85% yield. H NMR (300 MHz,
CDCl3): δ 1.45 (t, J = 5.4 Hz, 3H), 4.45 (q, J = 5.4 Hz, 2H), 7.45-
50 HRMS (ESI-FT) for C18H21NO5 [M +Na]+: calcd 354.1312, 105 7.49 (m, 1H), 7.53-7.56 (m, 1H), 7.90 (d, J = 6.0 Hz, 1H), 8.76 (d,
found: 354.1313.
J = 5.7 Hz, 1H), 8.91 (s, 1H); 13C NMR (100 MHz, CDCl3): δ
14.1, 62.6, 122.4, 125.4, 126.1, 126.4, 128.5, 130.7, 132.1, 136.6,
139.4, 143.8, 162.6, 178.9.
1
Compound 5m. Pink solid, 3.17 g, 80% yield. H NMR (300
MHz, CDCl3): δ 1.44 (t, J = 6.6 Hz, 3H), 1.70 (s, 9H), 3.89 (s,
3H), 4.43 (q, J = 7.2 Hz, 2H), 7.47-7.51 (m, 1H), 8.21-8.25 (m,
55 1H), 8.37 (s, 1H), 8.74-8.75 (m, 1H); 13C NMR (100 MHz,
General procedure for Rh-catalyzed 1,2-addition.
110 Under Ar atmosphere, a solution of α-ketoesters (0.25 mmol),
4
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Organic & Biomolecular Chemistry
[Rh(COE)2Cl]2 (2.7 mg, 0.0075 mmol of Rh), ligand 1 (2.0 mg,
0.00825 mmol), and arylboronic acid (0.375 mmol) in 1.0 mL of
THF was stirred at rt for 30 min. To this mixture were added
Compound 7l. Colorless oil, 80 mg, 78% yield, 95% ee. 1H
NMR (300 MHz, CDCl3): δ 1.26 (t, J = 5.4 Hz, 3H), 1.66 (s, 9H),
2.34 (s, 3H), 4.26 (s, 1H), 4.29-4.37 (m, 2H), 7.10-7.15 (m, 2H),
aqueous KOH (0.25 mL, 0.1 M, 0.025 mmol). After being stirred 60 7.23 (t, J = 5.7 Hz, 1H), 7.26-7.33 (m, 2H), 7.37-7.39 (m, 2H),
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5
at rt for 12 h, the mixture was concentrated under reduced
pressure. The residue was purified by silica gel column
chromatography to afford the corresponding addition product 7,
8 or 9.
7.56 (s, 1H), 8.11-8.13 (m, 1H); 13C NMR (100 MHz, CDCl3): δ
14.0, 21.6, 28.1, 63.0, 83.9, 115.0,121.6, 122.0, 122.5, 123.9,
124.4, 125.0, 127.2, 128.0, 128.4, 129.0, 135.9, 137.9,
140.3,149.6, 174.1; MS m/z (ESI, relative intensity) 432
65 ([M+Na]+, 10), 392 (11), 336 (100); HRMS (ESI-FT) for
C24H27NO5 [M +Na]+: calcd 432.1787, found 432.1790.
1
Compound 7c. Colorless oil 100 mg, 94% yield, 95% ee. H
10 NMR (300 MHz, CDCl3): δ 1.25 (t, J = 5.7 Hz, 3H), 1.66 (s, 9H),
3.80 (s, 3H), 4.24-4.35 (m, 3H), 6.86 (d, J = 8.7 Hz, 2H), 7.11 (t,
J = 7.2 Hz, 1H), 7.25-7.30 (m, 1H), 7.36 (d, J = 8.4 Hz, 1H),
7.44-7.47 (m, 2H), 7.56 (s, 1H), 8.11-8.13 (m, 1H); 13C NMR
1
Compound 7m. Colorless oil, 85 mg, 80% yield, 96% ee. H
NMR (300 MHz, CDCl3): δ 1.27 (t, J = 5.4 Hz, 3H), 1.67 (s, 9H),
3.78 (s, 3H), 4.29-4.40 (m, 3H), 6.86-6.89 (m, 1H), 7.11-7.17 (m,
(100 MHz, CDCl3): δ 14.0, 28.1, 55.2, 63.0, 83.9, 113.5, 115.0, 70 3H),, 7.25-7.31 (m, 2H), 7.41 (d, J = 6.0 Hz, 1H) , 7.55 (s, 1H),
15 121.6, 122.1, 122.5, 124.4, 124.9, 128.1, 128.4, 132.5, 135.9,
149.6, 159.4, 174.2; MS m/z (ESI, relative intensity) 449
([M+Na+H]+, 48), 352 (100), 308 (25); HRMS (ESI-FT) for
C24H27NO6 [M +Na]+: calcd 448.1736, found 448.1724.
8.11-8.13 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 14.0, 28.1,
55.2, 63.1, 83.9, 112.5,113.6, 115.0, 119.2, 121.5, 121.8, 122.6,
124.4, 125.0, 128.3, 129.1, 135.8, 141.9, 149.6, 159.4, 173.9; MS
m/z (ESI, relative intensity) 448 ([M+Na]+, 11), 352 (100);
75 HRMS (ESI-FT) for C24H27NO6 [M +Na]+: calcd 448.1736,
found 448.1744.
Compound 7h. Colorless oil 89 mg, 87% yield, 95% ee. 1H
20 NMR (300 MHz, CDCl3): δ 1.26 (t, J = 5.4 Hz, 3H), 1.66 (s, 9H),
2.35 (s, 3H), 4.25-4.38 (m, 3H), 7.10-7.16 (m, 3H), 7.26-7.30 (m,
1H), 7.37 (d, J = 6.0 Hz, 1H), 7.42 (d, J = 6.3 Hz, 2H), 7.56 (s,
1H), 8.11-8.13 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 14.0,
Compound 7n. Colorless oil, 75 mg, 70% yield, 95% ee. 1H
NMR (300 MHz, CDCl3): δ 1.28 (t, J = 5.4 Hz, 3H), 1.67 (s, 9H),
4.27-4.40 (m, 3H), 7.11-7.15 (m, 1H), 7.25-7.27 (m, 1H),, 7.29-
21.1, 28.1, 63.0, 83.9, 115.0, 121.6, 122.0, 122.5, 124.4, 125.0, 80 7.32 (m, 2H),7.36 (d, J = 6.0 Hz, 1H) 7.44-7.47 (m, 1H), 7.54 (s,
25 126.7, 128.4, 128.9, 135.9, 137.5, 138.0, 149.6, 174.2; MS m/z
(ESI, relative intensity) 432 ([M+Na]+, 11), 336 (100), 292 (12);
HRMS (ESI-FT) for C24H27NO5 [M +Na]+: calcd 432.1787,
found 432.1782.
1H), 7.60-7.61 (m, 1H), 8.11-8.12 (m, 1H); 13C NMR (100 MHz,
CDCl3): δ 14.0, 28.1, 63.4, 84.1, 113.7, 115.1, 115.0, 121.3,
122.7, 124.6, 124.8, 125.2, 127.0, 128.1, 128.4, 129.4, 130.4,
134.2, 135.8, 142.3, 149.6, 173.4; MS m/z (ESI, relative intensity)
85 452 ([M+Na]+, 13), 356 (100), 312 (14); HRMS (ESI-FT) for
C23H24ClNO5 [M +Na]+: calcd 452.1241, found 452.1252.
Compound 7i. Colorless oil 79 mg, 80% yield, 97% ee. 1H NMR
30 (300 MHz, CDCl3): δ 1.28 (t, J = 5.4 Hz, 3H), 1.66 (s, 9H), 4.28-
4.38 (m, 3H), 7.12 (t, J = 6.0 Hz, 1H), 7.26-7.30 (m, 1H), 7.34-
7.38 (m, 4H), 7.55-7.58 (m, 3H), 8.12-8.14 (m, 1H); 13C NMR
(100 MHz, CDCl3): δ 14.0, 28.1, 63.1, 83.9, 115.1, 121.5, 121.9,
Compound 7o. Colorless oil, 76 mg, 74% yield, 95% ee. 1H
NMR (300 MHz, CDCl3): δ 1.28 (t, J = 5.4 Hz, 3H), 1.67 (s, 9H),
4.27-4.47 (m, 3H), 7.13 (t, J = 5.4 Hz, 1H), 7.25-7.27 (m, 1H),,
122.6, 124.4, 125.0, 126.8, 128.2, 128.3, 135.9, 140.3, 149.6, 90 7.29-7.32 (m, 2H), 7.36 (d, J = 6.0 Hz, 1H) , 7.44-7.47 (m, 1H),
35 174.0; MS m/z (ESI, relative intensity) 418 ([M+Na]+, 26), 322
(100), 278 (11); HRMS (ESI-FT) for C23H25NO5 [M +Na]+: calcd
418.1630, found 418.1618.
7.55 (s, 1H), 7.61 (s, 1H), 8.11-8.13 (m, 1H); 13C NMR (100
MHz, CDCl3): δ 20.2, 23.0, 58.2, 79.0, 110.0, 116.17, 116.24,
117.5 (2JCF = 18 Hz), 119.6 (2JCF = 16 Hz), 120.0, 121.9, 122.9,
123.3, 124.2, 129.0, 130.7, 137.2, 144.4, 168.3; MS m/z (ESI,
95 relative intensity) 436 ([M+Na]+, 15), 340 (100), 296 (11);
HRMS (ESI-FT) for C23H24FNO5 [M +Na]+: calcd 436.1536,
found 436.1546.
Compound 7j. Colorless oil 91 mg, 85% yield, 96% ee. 1H NMR
(300 MHz, CDCl3): δ 1.27 (t, J = 5.4 Hz, 3H), 1.67 (s, 9H), 4.26-
40 4.40 (m, 3H), 7.12 (t, J = 6.0 Hz, 1H), 7.27-7.35 (m, 4H), 7.51 (d,
J = 6.3 Hz, 2H), 7.55 (s, 1H), 8.10-8.13 (m, 1H); 13C NMR (100
MHz, CDCl3): δ 14.0, 28.1, 63.3, 84.1, 115.1, 121.4, 121.5, 122.7,
124.6, 124.8, 128.1, 128.3, 134.2, 135.9, 138.9, 149.6, 173.6; MS
Compound 7p. Colorless oil, 87 mg, 78% yield, 94% ee. 1H
NMR (300 MHz, CDCl3): δ 1.14 (t, J = 5.4 Hz, 3H), 1.68 (s, 9H),
m/z (ESI, relative intensity) 452 ([M+Na]+, 27), 356 (100), 102 100 4.20-4.34 (m, 3H), 7.12 (t, J = 5.4 Hz, 1H), 7.26-7.34 (m, 3H),
45 (23); HRMS (ESI-FT) for C23H24ClNO5 [M +Na]+: calcd
452.1241, found 452.1227.
7.46-7.54 (m, 3H),, 7.77 (s, 1H), 7.83-7.85 (m, 1H), 7.87-7.90 (m,
1H), 8.21-8.23 (m, 1H), 8.26-8.29 (m, 1H); 13C NMR (100 MHz,
CDCl3): δ 13.9, 28.2, 63.0, 84.0, 115.1, 122.5, 122.7, 124.5,
125.0, 125.1, 126.3, 127.3, 128.9, 129.8, 134.4, 149.5, 175.1; MS
105 m/z (ESI, relative intensity) 468 ([M+Na]+, 31), 372 (100), 328
(12); HRMS (ESI-FT) for C27H27NO5 [M +Na]+: calcd 468.1787,
found 468.1778.
Compound 7k. Colorless oil 87 mg, 84% yield, 96% ee. 1H
NMR (300 MHz, CDCl3): δ 1.26 (t, J = 5.6 Hz, 3H), 1.66 (s, 9H),
4.26-4.40 (m, 3H), 7.03 (t, J = 6.3 Hz, 2H), 7.12 (t, J = 6.0 Hz,
50 1H), 7.27-7.31 (m, 1H), 7.34 (d, J = 5.7 Hz, 1H), 7.52-7.56 (m,
3H), 8.11-8.13 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 14.0,
2
28.1, 63.2, 84.1, 115.0 (d, JCF = 22 Hz), 121.4, 121.8, 122.6,
Compound 7q. Colorless oil, 90 mg, 81% yield, 93% ee. 1H
NMR (300 MHz, CDCl3): δ 1.27 (t, J = 5.4 Hz, 3H), 1.67 (s, 9H),
1
124.6, 124.8, 128.7, 128.8, 136.1, 136.2, 149.6, 162.6 (d, JCF
=
245 Hz), 173.8; MS m/z (ESI, relative intensity) 436 ([M+Na]+, 110 4.28-4.40 (m, 2H), 4.42 (s, 1H), 7.08 (t, J = 6.0 Hz, 1H), 7.28 (t, J
55 26), 340 (100), 296 (19); HRMS (ESI-FT) for C23H24FNO5 [M
+Na]+: calcd 436.1536, found 436.1522.
= 5.7 Hz, 1H), 7.38 (d, J = 6.0 Hz, 1H), 7.48-7.51 (m, 2H), 7.62-
7.65 (m, 2H), 7.80-7.85 (m, 3H), 8.08 (s, 1H), 8.13-8.16 (m, 1H);
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Journal Name, [year], [vol], 00–00 | 5

Organic & Biomolecular Chemistry
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1
13C NMR (100 MHz, CDCl3): δ 14.1, 28.1, 63.2, 84.0, 115.1,
121.6, 122.6, 124.5, 124.9, 125.0, 125.8, 126.1, 126.4, 127.5,
127.9, 128.5, 149.6, 174.0; MS m/z (ESI, relative intensity) 468
([M+Na]+, 10), 428 (21), 372 (100); HRMS (ESI-FT) for
C27H27NO5 [M +Na]+: calcd 468.1787, found 468.1804.
Compound 7w. Colorless oil 116 mg, 92% yield, 97% ee. H
NMR (300 MHz, CDCl3): δ 1.24 (t, J = 5.4 Hz, 3H), 1.64 (s, 9H),
3.79 (s, 3H), 4.24 (s, 1H), 4.25-4.34 (m, 2H), 6.85 (d, J = 6.6 Hz,
2H), 7.17-7.22 (m, 2H), 7.38 (d, J = 6.6 Hz, 2H), 7.53 (s, 1H),
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5
60 8.33 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 14.1, 28.1, 55.2,
63.1, 84.5, 113.6, 118.3, 122.0, 122.8, 125.2, 125.8, 127.2, 128.0,
132.3, 149.2, 159.5, 174.0; MS m/z (ESI, relative intensity) 528
([M+Na+2]+, 11), 526([M+Na]+, 12), 488 (52), 432 (100); HRMS
(ESI-FT) for C24H26BrNO6 [M +Na]+: calcd 526.0841, found
65 526.0851.
Compound 7r. Colorless oil, 75 mg, 68% yield, 40% ee. 1H
NMR (300 MHz, CDCl3): δ 1.30 (t, J = 5.4 Hz, 3H), 1.64 (s, 9H),
2.25 (s, 3H), 3.81 (s, 3H), 4.18 (s, 1H), 4.24-4.45 (m, 2H), 6.86 (d,
J = 6.9 Hz, 2H), 6.96 (d, J = 5.4 Hz, 1H), 7.20 (t, J = 6.0 Hz, 1H),
10 7.30 (s, 1H), 7.44 (d, J = 6.6 Hz, 2H), 8.04-8.06 (m, 1H); 13
C
NMR (100 MHz, CDCl3): δ 14.1, 21.5, 28.1, 55.2, 62.9, 83.9,
112.6, 113.4, 122.4, 124.6, 125.5, 126.2, 127.3, 127.9, 131.8,
133.8, 136.7, 149.4, 159.3, 174.7; MS m/z (ESI, relative intensity)
462 ([M+Na]+, 48), 422 (100), 366 (91); HRMS (ESI-FT) for
15 C25H29NO6 [M +Na]+: calcd 462.1893, found 462.1871.
Compound 7x. Colorless oil, 95 mg, 87% yield, 96% ee. 1H
NMR (300 MHz, CDCl3): δ 1.26 (t, J = 5.4 Hz, 3H), 1.62 (s, 9H),
2.61 (s, 3H), 3.81 (s, 3H), 4.24 (s, 1H), 4.26-4.37 (m, 2H), 6.85-
6.87 (m, 2H), 7.00-7.08 (m, 2H), 7.18 (d, J = 6.6 Hz, 1H), 7.44 (d,
70 J = 6.9 Hz, 2H), 7.50 (s, 1H); 13C NMR (100 MHz, CDCl3): δ
14.1, 22.2, 28.0, 55.2, 62.9, 83.6, 113.4, 119.3, 121.6, 122.9,
125.1, 127.2, 127.7, 128.2, 129.6, 132.5, 135.5, 149.4, 159.3,
174.3; MS m/z (ESI, relative intensity) 462 ([M+Na]+, 23), 422
(84), 366 (100); HRMS (ESI-FT) for C25H29NO6 [M +Na]+: calcd
75 462.1893, found 462.1888.
Compound 7s. Colorless oil, 87 mg, 79% yield, 95% ee. 1H
NMR (300 MHz, CDCl3): δ 1.26 (t, J = 5.4 Hz, 3H), 1.65 (s, 9H),
2.34 (s, 3H), 3.81 (s, 3H), 4.23 (s, 1H), 4.25-4.39 (m, 2H), 6.87 (d,
J = 6.9 Hz, 2H), 7.10 (d, J = 7.5 Hz, 1H), 7.19 (s, 1H), 7.46-7.48
20 (m, 3H), 7.98-8.01 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 14.0,
21.4, 28.1, 55.2, 63.0, 83.7, 113.5, 114.7, 121.3, 121.8, 125.0,
125.9, 128.0, 128.5, 132.0, 132.5, 159.3, 174.3; MS m/z (ESI,
relative intensity) 462 ([M+Na]+, 44), 422 (68), 366 (100), 322
(11); HRMS (ESI-FT) for C25H29NO6 [M +Na]+: calcd 462.1893,
25 found 462.1889.
Compound 7y. Colorless oil, 79 mg, 73% yield, 95% ee. 1H
NMR (300 MHz, CDCl3): δ 1.21 (t, J = 5.4 Hz, 3H), 1.67 (s, 9H),
2.30 (s, 3H), 3.84 (s, 3H), 4.17 (s, 1H), 4.20-4.37 (m, 2H), 6.85-
6.90 (m, 3H), 7.00 (t, J = 5.4 Hz, 1H), 7.17 (t, J = 5.4 Hz, 1H)
80 7.52 (d, J = 6.6 Hz, 2H), 8.07 (d, J = 6.3 Hz, 1H); 13C NMR (100
MHz, CDCl3): δ 13.8, 15.3, 28.2, 55.2, 62.9, 84.0, 113.5, 114.9,
118.9, 120.0, 122.2, 123.1, 128.1, 128.2, 133.7, 135.6, 136.5,
150.5, 159.3, 175.2; MS m/z (ESI, relative intensity) 462
([M+Na]+, 62), 422 (76), 366 (100); HRMS (ESI-FT) for
85 C25H29NO6 [M +Na]+: calcd 462.1893, found 462.1871.
Compound 7t. Colorless oil, 85 mg, 75% yield, 95% ee. 1H
NMR (300 MHz, CDCl3): δ 1.27 (t, J = 5.4 Hz, 3H), 1.64 (s, 9H),
3.70 (s, 3H), 3.81 (s, 3H), 4.27 (s, 1H), 4.28-4.36 (m, 2H), 6.77 (d,
J = 1.5 Hz, 1H), 6.83-6.90 (m, 3H), 7.46 (d, J = 6.6 Hz, 2H), 7.51
30 (s, 1H), 7.99-8.01 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 14.1,
28.1, 55.2, 55.5, 63.0, 83.8, 104.1, 105.0, 113.2, 113.5, 114.7,
115.7, 116.0, 121.8, 125.5, 128.1, 129.2, 132.4, 155.5, 159.4,
174.2; MS m/z (ESI, relative intensity) 478 ([M+Na]+, 8), 438
(76), 382 (100); HRMS (ESI-FT) for C25H29NO7 [M +Na]+: calcd
35 478.1842, found 478.1835.
Compound 8a. Colorless oil, 77 mg, 95% yield, 95% ee. 1H
NMR (300 MHz, CDCl3): δ 1.25 (t, J = 5.4 Hz, 3H), 3.81 (s, 3H),
4.29-4.34 (m, 3H), 6.86-6.90 (m, 2H), 7.15 (t, J = 5.4 Hz, 1H),
7.25-7.29 (m, 1H), 7.40 (d, J = 4.0 Hz, 1H), 7.45-7.49 (m, 3H),
90 7.59 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 14.0, 55.2, 63.1,
111.4, 113.6, 121.9, 122.6, 124.4, 125.9, 127.9, 132.3, 143.6,
155.7, 159.5, 173.9; MS m/z (ESI, relative intensity) 349
([M+Na]+, 52), 309 (100); HRMS (ESI-FT) for C19H18O5 [M
+Na]+: calcd 349.1052, found 349.1051.
1
Compound 7u. Colorless oil, 111 mg, 88% yield, 93% ee. H
NMR (300 MHz, CDCl3): δ 1.26 (t, J = 5.4 Hz, 3H), 1.64 (s, 9H),
3.80 (s, 3H), 4.24 (s, 1H), 4.26-4.38 (m, 2H), 6.86 (d, J = 6.6 Hz,
2H), 7.34-7.37 (m, 1H), 7.39 (d, J = 6.9 Hz, 2H), 7.53 (d, J = 1.5
40 Hz, 1H), 7.56 (s, 1H) 7.98-8.00 (m, 1H); 13C NMR (100 MHz, 95 Compound 8b. Colorless oil, 62 mg, 75% yield, 95% ee. 1H
CDCl3): δ 14.0, 28.1, 55.3, 63.2, 84.4, 113.6, 116.0, 116.5, 121.4,
124.3, 126.0, 127.3, 127.9, 130.0, 132.2, 134.7, 149.2, 159.5,
173.9; MS m/z (ESI, relative intensity) 528 ([M+Na+2]+, 9),
526([M+Na]+, 11), 488 (67), 432 (100); HRMS (ESI-FT) for
45 C24H26BrNO6 [M +Na]+: calcd 526.0841, found 526.0852.
NMR (300 MHz, CDCl3): δ 1.26 (t, J = 5.4 Hz, 3H), 4.30-4.36 (m,
3H), 7.15 (t, J = 5.7 Hz, 1H), 7.28-7.38 (m, 4H), 7.47-7.52 (m,
3H), 7.59 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 14.0, 29.7,
63.4, 111.6, 121.6, 122.8, 124.7, 128.1, 128.5, 134.3, 138.6,
100 143.4, 155.7, 173.4; MS m/z (ESI, relative intensity) 353
([M+Na]+, 100), 313 (62); HRMS (ESI-FT) for C18H15ClO4 [M
+Na]+: calcd 353.0557, found 353.0539.
1
Compound 7v. Colorless oil, 103 mg, 84% yield, 96% ee. H
NMR (300 MHz, CDCl3): δ 1.24 (t, J = 5.4 Hz, 3H), 1.64 (s, 9H),
2.43 (s, 3H), 3.79 (s, 3H), 4.21 (s, 1H), 4.25-4.36 (m, 2H), 6.84 (d,
J = 6.9 Hz, 2H), 6.93 (d, J = 6.3 Hz, 1H), 7.21 (d, J = 6.0 Hz, 1H),
Compound 9. Colorless oil, 71 mg, 83% yield, 97% ee. 1H NMR
(300 MHz, CDCl3): δ 1.23 (t, J = 5.4 Hz, 3H), 3.82 (s, 3H), 4.29-
50 7.42 (d, J = 6.6 Hz, 2H), 7.48 (s, 1H), 7.97 (s, 1H); 13C NMR 105 4.35 (m, 3H), 6.88-6.91 (m, 2H), 7.23-7.33 (m, 3H), 7.49 (d, J =
(100 MHz, CDCl3): δ 14.1, 21.9, 28.1, 55.2, 63.0, 83.7, 113.4,
115.3, 121.2, 122.0, 124.0, 124.2, 126.0, 128.1, 132.6, 134.4,
136.4, 149.7, 159.3, 174.2; MS m/z (ESI, relative intensity) 462
([M+Na]+, 11), 422 (83), 366 (100); HRMS (ESI-FT) for
55 C25H29NO6 [M +Na]+: calcd 462.1893, found 462.1887.
6.9 Hz, 2H), 7.66 (d, J = 6.9 Hz, 1H), 7.81 (d, J = 6.0 Hz, 1H);
13C NMR (100 MHz, CDCl3): δ 15.8, 57.0, 64.8, 115.2, 124.4,
125.7, 126.0, 127.6, 129.8, 134.2, 138.5, 138.9, 142.5, 161.1,
175.8; MS m/z (ESI, relative intensity) 365 ([M+Na]+, 37), 325
110 (100); HRMS (ESI-FT) for C19H18SO4 [M +Na]+: calcd 365.0823,
found 365.0813.
6
| Journal Name, [year], [vol], 00–00
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Page 7 of 8
Organic & Biomolecular Chemistry
G. R. Ganci and J. D. Chisholm, Tetrahedron Lett. 2007, 48, 8266; (d)
Acknowledgements
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We are grateful for financial support from the National Natural
Science Foundation of China (20972172, 21021063), the Chinese
Academy of Sciences, SIMM, and National Science
Technology Major Project.
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