Highly efficient and generalized asymmetric synthesis of quaternary stereogenic carbon-containing β-amino indanones/indanoles via Mannich-type additions between 1-indanones and N-tert-butanesulfinylketimines

Article abstract of DOI:10.1039/c4ob00489b

Here we report that, unlike other ketones, 1-indanone and acetophenone derived enolates undergo Mannich-type addition reactions with N-tert-butanesulfinyl ketimines with excellent yields (up to 98%) and diastereoselectivity (>99/1). The resulting compounds represent a new type of biologically relevant β-aminoketone derivative bearing quaternary stereogenic carbon, which could be further converted into the corresponding β-amino ketones and β-amino alcohols, possessing three consecutive stereogenic centres. This journal is

Full text of DOI:10.1039/c4ob00489b

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Biomolecular Chemistry
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Highly efficient and generalized asymmetric
synthesis of quaternary stereogenic carbon-
containing β-amino indanones/indanoles via
Mannich-type additions between 1-indanones
and N-tert-butanesulfinylketimines†
Cite this: Org. Biomol. Chem., 2014,
12, 4620
Lingmin Wu,a Chen Xie,a Haibo Mei,a Vadim A. Soloshonok,b,c Jianlin Han*a,d,e and
Yi Pana
Here we report that, unlike other ketones, 1-indanone and acetophenone derived enolates undergo
Mannich-type addition reactions with N-tert-butanesulfinyl ketimines with excellent yields (up to 98%)
and diastereoselectivity (>99/1). The resulting compounds represent a new type of biologically relevant
β-aminoketone derivative bearing quaternary stereogenic carbon, which could be further converted into
the corresponding β-amino ketones and β-amino alcohols, possessing three consecutive stereogenic
centres.
Received 4th March 2014,
Accepted 29th April 2014
DOI: 10.1039/c4ob00489b
www.rsc.org/obc
compounds possessing quaternary stereogenic centres still pre-
sents a formidable synthetic challenge.4 From a conceptual
Introduction
β-Amino carbonyl compounds are key intermediates in the pro- standpoint, the Mannich-type reactions between enolizable
duction of numerous nitrogen-containing natural products ketones and (S)- or (R)-N-tert-butanesulfinyl ketimines would
and pharmaceuticals, in particular amino alcohols, amino present an ideal approach for asymmetric synthesis of quatern-
acids, peptides and lactams.1 Among numerous approaches ary β-amino carbonyl compounds. However, quite surprisingly,
for preparation of β-amino ketones,2,3 the Mannich reaction this type of Mannich-type reaction has virtually not been
has been proven to be the most generalized and reliable studied.5 Thus, there is only a handful of data on the additions
method.4 In its classic version, the Mannich reaction involves of only ester enolates and not a single report dealing with the
a carbon–carbon bond formation via addition of an enolizable reactions of butanesulfinyl ketimines with ketone derived eno-
ketone to an in situ formed Schiff base. Since most of the lates.5,6 Furthermore, there is only one example of the corres-
Mannich reaction products contain a stereogenic carbon, the ponding product possessing a quaternary stereogenic carbon
issue of stereocontrol in these reactions has received consider- next to another α-stereogenic carbon.6e One of the reasons that
able attention.3
this chemistry of promising synthetic potential remains practi-
Nevertheless, in spite of the significant methodological cally unexplored is the notably lower reactivity of N-tert-butane-
developments in this area, preparation of β-amino carbonyl sulfinyl ketimines, as compared with the corresponding
aldimines.5,6 Additionally, N-tert-butanesulfinyl ketimines are
configurationally unstable and undergo easy enaminolization;
aSchool of Chemistry and Chemical Engineering, Nanjing University, Nanjing,
210093, China. E-mail: hanjl@nju.edu.cn; Fax: +86-25-83593153;
Tel: +86-25-83593153
their reactivity and structural factors plague their synthetic
applications.
Following our interest in the chemistry of N-tert-butane-
sulfinyl imines7 and synthesis of biologically relevant β-trifluoro-
methyl-β-amino indanone derivatives,8 we found that unlike
other ketones, 1-indanone and acetophenone derived enolates
undergo clean Mannich-type addition reactions with N-tert-
butanesulfinyl ketimines with an excellent stereochemical
outcome (up to 98% yields and 100/1 diastereoselectivity). The
resulting products represent a new type of biologically relevant
β-amino indanone derivative9–11 containing amino group-
bDepartment of Organic Chemistry I, Faculty of Chemistry, University of the Basque
Country UPV/EHU, 20018 San Sebastian, Spain
cIKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain
dInstitute for Chemistry & BioMedical Sciences, Nanjing University, Nanjing, 210093,
China
eHigh-Tech Research Institute of Nanjing University, Changzhou, 213164, China
†Electronic supplementary information (ESI) available: Experimental pro-
cedures, full spectroscopic data for compounds 3, 4 and 5 and copies of 1H NMR
and 13C NMR spectra. CCDC 951440. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c4ob00489b
4620 | Org. Biomol. Chem., 2014, 12, 4620–4627
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bearing quaternary stereogenic carbon. The scope and limit- metry between 1-indanone 1a and the base (LiHMDS) was
ations of these reactions, the mechanistic rationale for the examined showing that the use of 1.5 equiv. of 1a and
observed stereochemical outcome and synthetic elaboration of 1.7 equiv. of LiHMDS allows for optimized yields without any
the addition products into the corresponding free β-amino effect on the diastereoselectivity (entry 6, Table 1).
ketones and β-amino alcohols are also reported.
Another important reaction factor was found to be the
temperature. Elevating reaction temperature brought an
increase in the yield (up to 90%), but caused a dramatic
decrease in the diastereoselectivity (entries 7, 8). These results
suggested an experiment in which ketimine 2a was pre-cooled
to −78 °C before being added to the reaction mixture. As
shown in entry 9 this modification to the reaction procedure
gave a much improved stereochemical outcome confirming
the key role of the reaction temperature in the chemical yield
and diastereoselectivity.
With the optimized reaction conditions in hand, our next
goal was to explore the scope of these asymmetric Mannich-
type reactions. First, we studied a series of substituted keti-
mines 2b–l (Table 2). In general, all ketimines 2b–l easily
reacted with 1-indanone 1a under standard conditions allow-
ing preparation of the target products in good yields. In terms
of diastereoselectivity, the results obtained were rather un-
expected. Thus in the series of para-substituted derivatives 2b–h
(entries 2–8) we clearly observed some effect of the substituent
steric bulk on the diastereoselectivity. For example, the highest
level of selectivity (99 : 1) was observed in the series of
p-halogen substituted derivatives 2d–f (entries 4–6). By contrast,
in the reactions of ketimines bearing bulkier substituents,
such as 2b (p-Me, entry 2), 2c (p-MeO, entry 3), 2g (p-NO2,
entry 7) and 2h (p-CF3, entry 8) the observed diastereo-
selectivity was in the range of 100 : 3 to 95 : 5. It should be
emphasized that the electronic effect of the substituents was
unnoticeable in terms of diastereoselectivity. For example, keti-
Results and discussion
Taking advantage of our previous experience in asymmetric
Mannich-type additions of N-tert-butanesulfinyl imines with
C-nucleophiles,7,8,12 the preliminary scan of the reaction con-
ditions was focused on the following factors: the stoichiometry
of starting compounds, the nature of the base, the solvent and
the reaction temperature. We found that the use of equimolar
amounts of ketimine 2a and 1-indanone 1a is essential for
the reaction outcome (Table 1). Quite successful result was
obtained in the addition reaction conducted in THF in the
presence of LDA at −78 °C. The reaction proceeded cleanly,
affording the desired β-amino ketone 3a in 88% yield and with
92 : 8 diastereoselectivity (entry 1, Table 1). It should be noted
that with generation of two new stereogenic centres there
could possibly be up to four stereoisomeric products. Detailed
examination of the crude reaction mixtures by H-NMR allowed
clear detection of only two diastereomers. Application of
LiHMDS as the base (entry 2) led to a higher diastereo-
selectivity but also resulted in a lower yield. The use of stron-
ger bases gave rather interesting results. Thus in the series of
LiHMDS (entry 1), NaHMDS (entry 3) and KHMDS (entry 4) we
observed a notably worsening outcome, possibly indicating the
paramount importance of the coordinating/chelating pro-
perties of Li cations for the successful outcome of the reac-
tions under study. Switching back to Li-derived strong bases,
we also tried n-BuLi, which gave a rather disappointing yield
and diastereoselectivity (entry 5). Furthermore, the stoichio-
Table 2 Scope of N-tert-butanesulfinylketimines in the asymmetric
additionsa
Table 1 Optimization of reaction conditionsa
Entry
Ar
Product
Yieldb (%)
drc
1
2
3
4
5
6
7
8
9
10
C6H5
3a
3b
3c
3d
3e
3f
3g
3h
3i
92
89
83
94
93
94
98
95
81
76
83
82
98 : 2
97 : 3
95 : 5
99 : 1
99 : 1
99 : 1
97 : 3
96 : 4
91 : 9
90 : 10
93 : 7
93 : 7
Ratio
(1a/2a/base)
Temp
(°C)
Yielda
(%)
4-MeC6H4
4-MeOC6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
4-NO2C6H4
4-CF3C6H4
3-ClC6H4
3-BrC6H4
2-Furyl
Entry
Base
drb
1
2
3
4
5
6
7
8
9
LDA
1.0 : 1.0 : 1.0
1.0 : 1.0 : 1.0
1.0 : 1.0 : 1.0
1.0 : 1.0 : 1.0
1.0 : 1.0 : 1.0
1.5 : 1.0 : 1.7
1.0 : 1.0 : 1.0
1.0 : 1.0 : 1.0
1.5 : 1.0 : 1.7
−78
−78
−78
−78
−78
−78
−40
−40
−78
88
85
12
<5
54
90
93
91
92
92 : 8
93 : 7
89 : 11
n.d.c
87 : 13
93 : 7
LiHMDS
NaHMDS
KHMDS
n-BuLi
LiHMDS
LDA
3j
3k
3l
85 : 15 11
88 : 12 12
98 : 2d
LiHMDS
LiHMDS
2-Thienyl
a Reaction conditions: 1-indanone 1a (1.5 mmol), ketimine
2
a Isolated yields. b The ratio determined by 1H NMR on crude reaction (1.0 mmol), LiHMDS (1.7 mmol), THF (5 mL). b Isolated yields. c The
mixtures. c Not determined. d Ketimine 2a was pre-cooled to −78 °C, isomer ratio determined by 1H NMR integration of crude reaction
and then transferred via a cannula to the reaction mixture.
mixtures.
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mines 2c (p-MeO, entry 3) and 2h (p-CF3, entry 8) showed vir-
tually the same level of stereoselectivity. On the other hand,
the electronic effect had a notable impact on the chemical
yield. Thus, the lowest yield of 83% (entry 3) was obtained with
ketimine 2c (p-MeO) while the highest (98%, entry 7) was
observed in the reaction of ketimine 2g (p-NO2). The position
of the substituent on the aromatic ring of the acetophenone
moiety in ketimines 2a–l had an even more pronounced effect.
As one can see from the entries 9 and 10, in the reactions of
m-substituted imines 2i (m-Cl) and 2j (m-Br) the lowest
diastereoselectivity of about 91 : 9 was observed. As discussed
above, the same Cl- and Br-substituents but located in the
p-position in the imines 2e and 2f gave the highest selectivity
(99 : 1) (entry 5 vs. 9 and 6 vs. 10) in this study. Finally, we also
conducted the addition reactions of ketimines 2k (entry 11)
and 2l (entry 12) bearing 2-furyl and 2-thienyl rings, respecti-
vely. The results were rather satisfactory allowing preparation
of adducts 2k,l in reasonably good yields and diastereo-
selectivity. As one may agree, the data shown in Table 2 clearly
suggest a rather high degree of the scope of this asymmetric
Mannich-type reaction for preparation of β-amino indanones
bearing various substituents in the α-position to the amino
group.
Fig. 1 OPTER diagram of compound 3d.
Considering the unexpected and complex effect of the sub-
stituents in ketimines 2 on the stereochemical outcome of the
reactions under study, it was quite logical to have some pre-
liminary data on whether a similar effect can be observed
using derivatives of starting 1-indanone 1. As one can see from
Table 3, in all cases studied (entries 2–7) an excellent level of
diastereoselectivity (99 : 1) was observed and the target pro-
ducts were isolated with the yields exceeding 90%. The only
exception was the addition of 6-Me substituted indanone
(entry 1) resulting in a slightly lower yield and stereoselectivity.
While the range and position of the substituents studied is
Fig. 2 Proposed mechanism for the Mannich addition.
somehow limited, these preliminary results suggest that the
effect of substitution on the indanone component might not
be as dramatic as it is on the ketimine part.
To assign the absolute configuration of the two newly
created stereogenic centres, we performed crystallographic
analysis of compound 3d (Fig. 1). As revealed by the X-ray
study, the product 3d has the (S,R,SS) configuration. The absol-
ute configurations of other products 3 were assigned as
(S,R,SS) by analogy, based on the similarity of their spectro-
scopic and chiroptical properties.
Table 3 Scope of 1-indanones in the asymmetric Mannich-type
additionsa
To account for the observed reactivity, the effect of the sub-
stituents and the absolute configuration of products 3, we can
propose transition state (TS) A as shown in Fig. 2. The follow-
ing features were taken into consideration for construction of
a plausible TS in the reactions under study: first, TS A is cyclic,
chair-like,13 and Li chelated, accounting for the poor reactivity
in the case of Na- and K-cations; Second, the ketimines 2 react
in the (E)-geometric configuration, as it is known that imines
of this type exist as single stereoisomers.14 Finally, as it is
better seen from the Newman projection A′, the aromatic rings
of both indanone 1 and ketimines 2 are over each other ren-
dering TS A quite sensitive to the steric bulk and position of
the substituents, in particular, on the ketimine phenyl. On the
other hand, according to TS A, the substitution on the inda-
none aromatic ring, especially in the positions 5 and 6, might
have much lesser effect on its stability. Another mechanistic
Entry
R
Product
Yieldb (%)
drc
1
2
3
4
5
6
7
6-Me
6-F
6-Cl
6-Br
5-F
5-Cl
5-Br
3m
3n
3o
3p
3q
3r
86
96
91
94
95
90
93
97 : 3
99 : 1
99 : 1
99 : 1
99 : 1
99 : 1
99 : 1
3s
a Reaction conditions: 1-indanone 1a (1.5 mmol), ketimine
2
(1.0 mmol), LiHMDS (1.7 mmol), THF (5 mL). b Isolated yields. c The
isomer ratio determined by 1H NMR integration of crude reaction
mixtures.
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Table 4 Scope of acetophenone derivatives in the asymmetric
Mannich-type additionsa
Scheme 1 Deprotection of 3g.
Entry
R1
R2
Product
Yieldb (%)
drc
1
2
3
H
H
Br
H
NO2
Br
7a
7b
7c
52
65
73
99 : 1
99 : 1
99 : 1
a Reaction conditions: acetophenone derivatives
6
(1.5 mmol),
ketimine 2 (1.0 mmol), LiHMDS (1.7 mmol), THF (5 mL). b Isolated
yields. c The isomer ratio determined by 1H NMR integration of crude
reaction mixtures.
Scheme 2 Reduction of 3a.
conclusion one can draw based on these results is that the
configurational homogeneity is of paramount importance to
reduce the number of possible TSs15 and obtain high stereo-
chemical outcome. As in the present example, both reaction
partners, indanones 1 and ketimines 2, can react only in the
corresponding (E)-configurations, which can account for gen-
erally high level of the observed diastereoselectivity.
nol at room temperature (Scheme 1). Stirring the mixture for
two hours gave rise to the corresponding hydrochloride 4,
which was isolated in 92% yield.
For the second objective, we demonstrate that DIBAL can
be successfully used for highly stereoselective reduction of
β-amino ketone 3a to the corresponding β-amino alcohol 5,
isolated as a single product in 90% yield (Scheme 2). One may
agree that the whole process including the described here
Mannich-type addition reactions followed by DIBAL assisted
reduction provides quite a simple and synthetically sound
approach for preparation of enantiomerically pure β-amino
alcohols possessing three consecutive stereogenic centres.
In order to have some additional verification of the pro-
posed mechanistic rationale, we decided to conduct experi-
ments on the addition reactions between ketimines 2 and
aceto- and propiophenones. As one may expect,16 aceto-
phenone can form only one homogeneous enolate, and therefore
its reactions with imine 2a should be highly diastereoselective.
Quite agreeably, the addition of an acetophenone-derived
enolate with 2a afforded the product 7a (Table 4) with excellent
diastereoselectivity, although in a moderate chemical yield
(entry 1). Encouraged by this result, we conducted additional
experiments to briefly assess the generality of acetophenone-
type substrates in these reactions. As an example of substituted
imine reactions we studied the addition reaction of p-NO2-
imine 2 with acetophenone which gave the product 7b in 65%
yield and excellent (99 : 1) diastereoselectivity (entry 2). Finally,
as an example of a substituted acetophenone reaction, the
addition of p-Br-acetophenone with imine 2a was conducted.
The expected product 7c was isolated in a good yield and, once
again, with virtually complete stereoselectivity (entry 3). In
sharp contrast, the reaction of propiophenone, which is
expected to produce a mixture of (E)- and (Z)-enolates, virtually
did not proceed (∼5% yield of the mixture of products) under
the standard conditions. This outcome clearly highlighted the
anticipated sterically congested nature of the proposed TS A
(Fig. 2) as well as the importance of enolate homogeneity.
As the final objective of this work, we believed that it might
be important to demonstrate a preparation of free amino pro-
ducts as well as elaboration of compounds 3 to some more
synthetically complex derivatives. To this end we conducted
the deprotection of compound 3g with gaseous HCl in metha-
Conclusions
In summary, we have developed the first highly efficient asym-
metric Mannich-type addition reactions between N-tert-butane-
sulfinylketimines and indanone enolates. Preliminary results
also indicate that this type of asymmetric addition can be
extended to acetophenone derivatives, rendering the reported
results of greater synthetic potential. The compounds available
by these reactions represent a new family of biologically rele-
vant β-amino indanone derivatives bearing quaternary stereo-
genic carbon. The synthetic generality of this approach is
demonstrated by using different substituents on aromatic
rings of both 1-indanones and N-tert-butanesulfinylketimines.
In all cases studied, practically useful levels of diastereo-
selectivity and chemical yields are obtained. It is suggested
that the geometric homogeneity [(E)-configuration] of both
ketimines and indanone enolates is a key feature providing for
the excellent stereochemical outcome in these reactions. We
also showed that the addition products could be further highly
selectively converted into the corresponding free β-amino
ketones and β-amino alcohols, possessing three consecutive
stereogenic centres.
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General information
1H), 2.38 (s, 3H), 1.65 (s, 3H), 1.27 (s, 9H). 13C NMR (101 MHz,
CDCl3): δ 208.4, 153.9, 140.0, 137.4, 137.2, 135.4, 129.1, 127.7,
127.3, 126.4, 124.0, 62.5, 57.2, 56.2, 30.1, 22.9, 21.7, 21.1. IR
(cm−1): 3262, 2977, 2947, 2921, 2852, 1687, 1607, 1466, 1378,
1293, 1204, 1067, 1060, 851, 819, 754. HRMS (ESI): [M + H+]
calcd for: C22H28NO2S 370.1841, Found: 370.1848.
All reagents were obtained from commercial suppliers and
used without further purification. The reactions were con-
ducted in a closed system in an atmosphere of N2 and were
monitored by TLC. Solvents were dried and distilled prior to
use. Flash chromatography was performed using silica gel 60
(200–300 mesh). Thin layer chromatography was carried out on
3c: White solid (320 mg, 83%). mp 159–160 °C. [α]2D5 = 58.5
(c = 0.38, CHCl3). 1H NMR (400 MHz, CDCl3): δ 7.76 (d, J =
7.7 Hz, 1H), 7.58 (td, J = 7.6, 1.0 Hz, 1H), 7.45–7.32 (m, 4H),
6.94–6.88 (m, 2H), 6.14 (s, 1H), 3.84 (s, 3H), 3.22 (dd, J = 8.2,
4.4 Hz, 1H), 2.79 (dd, J = 18.0, 8.2 Hz, 1H), 2.53 (dd, J = 18.0,
4.4 Hz, 1H), 1.64 (s, 3H), 1.27 (s, 9H). 13C NMR (101 MHz,
CDCl3): δ 208.4, 159.0, 153.9, 137.2, 135.4, 135.0, 128.6, 127.7,
126.4, 124.0, 113.6, 62.4, 57.3, 56.1, 55.2, 30.1, 22.9, 21.7. IR
(cm−1): 3265, 2978, 2958, 2925, 2853, 1689, 1608, 1518, 1464,
1379, 1256, 1189, 1056, 1029, 844, 756, 740. HRMS (ESI):
[M + Na]+ calcd for: C22H27NNaO3S 408.1609, Found: 408.1610.
3d: White solid (351 mg, 94%). mp 112–113 °C. [α]2D5 = 98.6
(c = 1.05, CHCl3). 1H NMR (400 MHz, CDCl3): δ 7.77 (d, J =
silica gel 60 F-254 TLC plates of 20 cm × 20 cm. H, 13C and
1
19F NMR spectra were recorded on a Bruker AVANCE400M
spectrometer. Melting points are uncorrected. Values of
optical rotation were measured on a Rudolph Automatic
Polarimeter A21101. Infrared spectra were obtained on a
Bruker Vector 22 in KBr pellets. HRMS were conducted on an
Agilent 6540Q-TOF LC/MS equipped with an electrospray
ionization (ESI) probe operating in positive or negative ion
mode.
Typical procedure for asymmetric addition of sulfinylimine
Into an oven-dried reaction vial flushed with N2 was taken 7.7 Hz, 1H), 7.59 (td, J = 7.5, 1.1 Hz, 1H), 7.52–7.45 (m, 2H),
1-indanone 1 (1.5 mmol) and anhydrous THF (5.0 mL). The 7.42–7.33 (m, 2H), 7.12–7.04 (m, 2H), 6.19 (s, 1H), 3.20 (dd, J =
reaction vial was cooled to −78 °C and LiHMDS (2 M in THF, 8.2, 4.5 Hz, 1H), 2.78 (dd, J = 18.0, 8.2 Hz, 1H), 2.52 (dd, J =
0.85 mL) was added dropwise with stirring. After 40 min at 18.0, 4.4 Hz, 1H), 1.66 (s, 3H), 1.27 (s, 9H). 13C NMR
−78 °C, sulfinyl-imine 2 (1.0 mmol) dissolved in anhydrous (101 MHz, CDCl3): δ 208.0, 162.2 (d, JFC = 247.3 Hz), 153.7,
5
4
THF (2 mL) was pre-cooled to −78 °C, and then added drop- 138.8 (d, JFC = 3.2 Hz), 137.1, 135.5, 129.2 (d, JFC = 8.1 Hz),
3
wise to the reaction mixture. Stirring was continued at −78 °C 127.8, 126.4, 124.1, 115.2 (d, JFC = 21.3 Hz), 62.4, 57.1, 56.3,
for 24 h, and then the reaction was quenched with saturated 29.9, 22.9, 21.8. 19F NMR (376 MHz, CDCl3): δ −114.51. IR
NH4Cl (3.0 mL), followed by H2O (5.0 mL) and the mixture was (cm−1): 3665, 3256, 2981, 2961, 2925, 1686, 1606, 1512, 1467,
brought to room temperature. The organic layer was taken and 1379, 1286.9, 1226, 1206, 1169, 1066, 1060, 856, 754. HRMS
the aqueous layer was extracted with EtOAc (2 × 20 mL). The (ESI): [M + Na]+ calcd for: C21H24FNO2SNa 396.1409, Found:
combined organic layers were washed with water (1 × 30 mL) 396.1409.
and brine solution (1 × 30 mL) and dried over anhydrous
3e: White solid (362 mg, 93%). mp 175–176 °C. [α]2D5 = 60.0
Na2SO4. The solvent was evaporated, and the crude mixture (c = 1.01, CHCl3). 1H NMR (400 MHz, CDCl3): δ 7.77 (d, J =
was charged onto silica gel and purified by flash chromato- 7.7 Hz, 1H), 7.59 (t, J = 7.4 Hz, 1H), 7.49–7.33 (m, 6H), 6.19 (s,
graphy to furnish the corresponding product 3.
1H), 3.18 (dd, J = 8.1, 4.4 Hz, 1H), 2.78 (dd, J = 18.0, 8.2 Hz,
3a: White solid (327 mg, 92%). mp 199–200 °C. [α]2D5 = 89.0 1H), 2.52 (dd, J = 18.0, 4.3 Hz, 1H), 1.66 (s, 3H), 1.27 (s, 9H).
(c = 0.58, CHCl3). 1H NMR (400 MHz, CDCl3): δ 7.77 (d, J = 13C NMR (101 MHz, CDCl3): δ 207.9, 153.6, 141.7, 137.1, 135.6,
7.7 Hz, 1H), 7.58 (td, J = 7.5, 1.1 Hz, 1H), 7.54–7.49 (m, 2H), 133.7, 128.9, 128.6, 127.9, 126.4, 124.1, 62.4, 56.9, 56.3, 29.9,
7.43–7.30 (m, 5H), 6.19 (s, 1H), 3.24 (dd, J = 8.2, 4.4 Hz, 1H), 22.9, 21.6. IR (cm−1): 3257, 2978, 2924, 1685, 1606, 1465, 1293,
2.76 (dd, J = 18.1, 8.2 Hz, 1H), 2.54 (dd, J = 18.0, 4.4 Hz, 1H), 1207, 1093, 1068, 1061, 1012, 854, 753, 618. HRMS (ESI):
1.68 (s, 3H), 1.28 (s, 9H). 13C NMR (101 MHz, CDCl3): δ 208.3, [M + Na]+ calcd for: C21H24ClNO2SNa 412.1114, Found:
153.8, 142.9, 137.1, 135.5, 128.4, 127.7, 127.7, 127.4, 126.4, 412.1114.
124.0, 62.7, 57.1, 56.2, 30.0, 22.9, 21.6. IR (cm−1): 3259, 2954,
3f: White solid (407 mg, 94%). mp 178–179 °C. [α]2D5 = 42.3
2923, 2853, 1697, 1605, 1461, 1451, 1367, 1203, 1058, 780, 754, (c = 1.01, CHCl3). 1H NMR (400 MHz, CDCl3): δ 7.77 (d, J =
706, 614. HRMS (ESI): [M + Na]+ calcd for: C21H25NO2SNa 7.7 Hz, 1H), 7.59 (td, J = 7.6, 1.0 Hz, 1H), 7.55–7.50 (m, 2H),
378.1504, Found: 378.1503.
7.42–7.33 (m, 4H), 6.19 (s, 1H), 3.17 (dd, J = 8.2, 4.4 Hz, 1H),
1
3a′: H NMR (400 MHz, CDCl3): δ 7.69 (d, J = 7.7 Hz, 1H), 2.78 (dd, J = 18.0, 8.2 Hz, 1H), 2.51 (dd, J = 18.0, 4.4 Hz, 1H),
7.54 (td, J = 7.5, 1.0 Hz, 1H), 7.37–7.31 (m, 2H), 7.22–7.12 (m, 1.65 (s, 3H), 1.27 (s, 9H). 13C NMR (101 MHz, CDCl3): δ 207.9,
5H), 6.37 (s, 1H), 3.52 (dd, J = 8.2, 5.0 Hz, 1H), 3.36 (dd, J = 153.6, 142.2, 137.1, 135.6, 131.6, 129.2, 127.9, 126.4, 124.1,
17.2, 8.2 Hz, 1H), 3.02 (dd, J = 17.2, 5.0 Hz, 1H), 1.99 (s, 3H), 121.9, 62.5, 56.9, 56.3, 29.9, 22.9, 21.5. IR (cm−1): 3258, 2959,
1.30 (s, 9H).
2923, 1686, 1605, 1465, 1400, 1293, 1207, 1077, 1067, 1060,
3b: White solid (329 mg, 89%). mp 136–137 °C. [α]D25 = 68.3 1007, 851, 755, 615. HRMS (ESI): [M + Na]+ calcd for:
(c = 0.76, CHCl3). 1H NMR (400 MHz, CDCl3): δ 7.76 (d, J = C21H24BrNO2SNa 456.0609, Found: 456.0607.
7.7 Hz, 1H), 7.57 (td, J = 7.6, 1.0 Hz, 1H), 7.42–7.31 (m, 4H),
3g: Pale yellow solid (392 mg, 98%). mp 97–98 °C. [α]D25
=
7.19 (d, J = 8.0 Hz, 2H), 6.14 (s, 1H), 3.22 (dd, J = 8.2, 4.4 Hz, 27.1 (c = 1.02, CHCl3). 1H NMR (400 MHz, CDCl3): δ 8.26 (d, J =
1H), 2.77 (dd, J = 18.0, 8.2 Hz, 1H), 2.53 (dd, J = 18.0, 4.4 Hz, 8.9 Hz, 2H), 7.79 (d, J = 7.7 Hz, 1H), 7.72 (d, J = 8.9 Hz, 2H),
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7.62 (td, J = 7.6, 0.9 Hz, 1H), 7.45–7.35 (m, 2H), 6.33 (s, 1H), 7.8 Hz, 1H), 7.59 (t, J = 7.4 Hz, 1H), 7.42–7.33 (m, 3H),
3.22 (dd, J = 8.2, 4.5 Hz, 1H), 2.77 (dd, J = 17.8, 8.3 Hz, 1H), 7.08–7.04 (m, 1H), 6.97 (dd, J = 4.8, 3.9 Hz, 1H), 6.24 (s, 1H),
2.52 (dd, J = 17.8, 4.5 Hz, 1H), 1.74 (s, 3H), 1.29 (s, 9H). 3.21 (dd, J = 8.2, 4.4 Hz, 1H), 2.98 (dd, J = 18.0, 8.3 Hz, 1H),
13C NMR (101 MHz, CDCl3): δ 207.3, 153.3, 150.4, 147.4, 136.8, 2.68 (dd, J = 18.0, 4.4 Hz, 1H), 1.71 (s, 3H), 1.29 (s, 9H).
135.8, 128.5, 128.1, 126.5, 124.2, 123.6, 62.7, 56.7, 56.5, 29.7, 13C NMR (101 MHz, CDCl3): δ 207.2, 153.7, 149.0, 137.0,
22.8, 21.6. IR (cm−1): 3244, 2954, 2922, 1698, 1605, 1517, 1470, 135.6, 127.8, 126.5, 126.5, 126.2, 126.1, 124.1, 61.8, 58.5,
1346, 1066, 874, 856, 758, 703. HRMS (ESI): [M + Na]+ calcd 56.4, 30.1, 23.0, 22.8. IR (cm−1): 3241, 2923, 1686, 1607,
for: C21H24N2O4SNa 423.1354, Found: 423.1356.
1465, 1385, 1291, 1240, 1188, 1062, 971. HRMS (ESI):
Na]+ calcd for: C19H23NO2S2Na 384.1068, Found:
3h: White solid (402 mg, 95%). mp 134–135 °C. [α]2D5 = 75.1 [M
+
(c = 1.00, CHCl3). 1H NMR (400 MHz, CDCl3): δ 7.78 (d, J = 384.1066.
7.7 Hz, 1H), 7.70–7.57 (m, 5H), 7.44–7.33 (m, 2H), 6.26 (s, 1H),
3m: White solid (384 mg, 86%). mp 145–146 °C. [α]2D5 = 29.6
1
3.21 (dd, J = 8.1, 4.5 Hz, 1H), 2.76 (dd, J = 17.9, 8.2 Hz, 1H), (c = 1.00, CHCl3). H NMR (400 MHz, CDCl3): δ 7.57–7.48 (m,
2.51 (dd, J = 17.9, 4.4 Hz, 1H), 1.71 (s, 3H), 1.28 (s, 9H). 13C 3H), 7.43–7.35 (m, 3H), 7.28–7.20 (m, 1H), 6.21 (s, 1H), 3.16
NMR (101 MHz, CDCl3): δ 207.7, 153.5, 147.1, 137.0, 135.7, (dd, J = 7.8, 4.1 Hz, 1H), 2.72 (dd, J = 17.8, 8.1 Hz, 1H),
130.0 (q, 3JFC = 32.6 Hz), 128.0, 127.9, 126.4, 125.4 (q, 4JFC = 3.8 2.50–2.35 (m, 4H), 1.63 (s, 3H), 1.27 (s, 9H). 13C NMR
Hz), 124.2, 124.0 (q, JFC = 273.1 Hz), 62.7, 56.8, 56.5, 29.8, 22.9, (101 MHz, CDCl3): δ 207.9, 151.1, 142.3, 137.9, 137.2, 136.9,
21.6. 19F NMR (376 MHz, CDCl3): δ −62.54. IR (cm−1): 3257, 131.5, 129.3, 126.1, 123.9, 121.9, 62.5, 57.2, 56.3, 29.5, 22.9,
2978, 2925, 1686, 1608, 1467, 1414, 1380, 1325, 1289, 1208, 21.5, 21.1. IR (cm−1): 3255, 2977, 1686, 1493, 1399, 1284, 1163,
1167, 1124, 1074, 1069, 1058, 1015, 861, 840, 759, 750, 620. 1068, 850. HRMS (ESI): [M + H]+ calcd for: C22H27BrNO2S
HRMS (ESI): [M + Na]+ calcd for: C22H24F3NO2SNa 446.1378, 448.0946, Found: 448.0950.
Found: 446.1378.
3n: White solid (433 mg, 96%). mp 158–159 °C. [α]2D5 = 43.2
3i: White solid (315 mg, 81%). mp 146–147 °C. [α]D25 = 24.8 (c = 0.66, CHCl3). 1H NMR (400 MHz, CDCl3): δ 7.52 (d, J =
(c = 0.36, CHCl3). 1H NMR (400 MHz, CDCl3): δ 7.77 (d, J = 8.5 Hz, 2H), 7.42–7.35 (m, 3H), 7.34–7.29 (m, 2H), 6.05 (s, 1H),
7.7 Hz, 1H), 7.63–7.57 (m, 1H), 7.51 (s, 1H), 7.43–7.28 (m, 5H), 3.23 (dd, J = 8.0, 4.3 Hz, 1H), 2.75 (dd, J = 17.8, 8.1 Hz, 1H),
6.24 (s, 1H), 3.18 (dd, J = 8.1, 4.4 Hz, 1H), 2.80 (dd, J = 18.0, 2.48 (dd, J = 17.7, 3.7 Hz, 1H), 1.65 (s, 3H), 1.27 (s, 9H). 13C
5
8.2 Hz, 1H), 2.54 (dd, J = 18.0, 4.4 Hz, 1H), 1.66 (s, 3H), 1.29 (s, NMR (101 MHz, CDCl3): δ 207.0 (d, JFC = 2.9 Hz), 162.4 (d,
5
4
9H). 13C NMR (101 MHz, CDCl3): δ 207.9, 153.7, 145.3, 137.0, JFC = 249.2 Hz), 149.1 (d, JFC = 2.0 Hz), 141.9, 138.6 (d, JFC
=
=
4
3
135.6, 134.5, 129.7, 128.0, 127.9, 127.9, 126.5, 125.6, 124.1, 7.3 Hz), 131.6, 129.2, 127.9 (d, JFC = 8.0 Hz), 123.4 (d, JFC
3
62.6, 56.8, 56.4, 29.8, 22.9, 21.5. IR (cm−1): 3248, 2956, 2917, 23.8 Hz), 122.0, 109.8 (d, JFC = 21.8 Hz), 62.5, 57.8, 56.4, 29.4,
2850, 1695.3, 1606, 1473, 1419, 1379, 1290, 1206, 1060, 789. 22.8, 21.6. 19F NMR (376 MHz, CDCl3): δ −113.26. IR (cm−1):
HRMS (ESI): [M + Na]+ calcd for: C21H24ClNO2SNa 412.1114, 3262, 2978, 2961, 1690, 1488, 1442, 1400, 1266, 1076, 852.
Found: 412.1114.
HRMS (ESI): [M + Na]+ calcd for: C21H23BrFNO2SNa 474.0515,
3j: White solid (329 mg, 76%). mp 119–120 °C. [α]2D5 = 89.5 Found: 474.0514.
(c = 1,01, CHCl3). 1H NMR (400 MHz, CDCl3): δ 7.77 (d, J =
3o: White solid (425 mg, 91%). mp 137–138 °C. [α]2D5 = 23.5
7.7 Hz, 1H), 7.67 (t, J = 1.8 Hz, 1H), 7.60 (td, J = 7.6, 1.0 Hz, (c = 0.68, CHCl3). 1H NMR (400 MHz, CDCl3): δ 7.71 (s, 1H),
1H), 7.49–7.34 (m, 4H), 7.27 (t, J = 7.9 Hz, 1H), 6.22 (s, 1H), 7.57–7.49 (m, 3H), 7.37 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 8.1 Hz,
3.17 (dd, J = 8.2, 4.5 Hz, 1H), 2.80 (dd, J = 18.0, 8.2 Hz, 1H), 1H), 6.03 (s, 1H), 3.22 (dd, J = 7.9, 4.2 Hz, 1H), 2.75 (dd, J =
2.55 (dd, J = 18.0, 4.4 Hz, 1H), 1.65 (s, 3H), 1.28 (s, 9H). 18.0, 8.1 Hz, 1H), 2.48 (dd, J = 18.1, 4.0 Hz, 1H), 1.64 (s, 3H),
13C NMR (101 MHz, CDCl3): δ 207.8, 153.6, 145.6, 137.0, 135.6, 1.27 (s, 9H). 13C NMR (101 MHz, CDCl3): δ 206.5, 151.6, 141.9,
130.9, 130.9, 129.9, 127.9, 126.5, 126.0, 124.1, 122.7, 62.6, 56.9, 138.5, 135.6, 134.3, 131.6, 129.2, 127.7, 123.8, 122.1, 62.5, 57.5,
56.4, 29.9, 22.9, 21.5. IR (cm−1): 3273, 2973, 2958, 2924, 1694, 56.4, 29.6, 22.9, 21.6. IR (cm−1): 3262, 2978, 2961, 2926, 1692,
1567, 1474, 1463, 1368, 1291, 1204, 1064, 1024, 856. HRMS 1468.3, 1399, 1240, 1196, 1078, 1060, 1007, 850, 837, 719.
(ESI): [M + H]+ calcd for: C21H25BrNO2S 434.0789, Found: HRMS (ESI): [M + Na]+ calcd for: C21H23BrClNO2SNa 490.0219,
434.0790.
3k: Yellow solid (286 mg, 83%). mp 147–148 °C. [α]2D5 = 51.5
Found: 490.0222.
3p: White solid (482 mg, 94%). mp 170–171 °C. [α]2D5 = 9.8
(c = 1.03, CHCl3). 1H NMR (400 MHz, CDCl3): δ 7.76 (d, J = (c = 0.69, CHCl3). 1H NMR (400 MHz, CDCl3): δ 7.88 (d, J =
7.7 Hz, 1H), 7.63–7.57 (m, 1H), 7.45–7.35 (m, 3H), 5.81 (s, 1H), 1.4 Hz, 1H), 7.69 (dd, J = 8.1, 1.7 Hz, 1H), 7.52 (d, J = 8.6 Hz,
3.46 (dd, J = 8.3, 4.4 Hz, 1H), 3.02 (dd, J = 17.9, 8.3 Hz, 1H), 2H), 7.37 (d, J = 8.6 Hz, 2H), 7.26 (d, J = 7.0 Hz, 1H), 6.02 (s,
2.63 (dd, J = 17.9, 4.4 Hz, 1H), 1.59 (s, 3H), 1.24 (s, 9H). 13C 1H), 3.21 (dd, J = 8.1, 4.4 Hz, 1H), 2.73 (dd, J = 18.1, 8.2 Hz,
NMR (101 MHz, CDCl3): δ 207.8, 155.0, 153.6, 142.6, 137.1, 1H), 2.45 (dd, J = 18.1, 4.3 Hz, 1H), 1.64 (s, 3H), 1.26 (s, 9H).
135.5, 127.7, 126.4, 123.9, 110.1, 109.4, 59.7, 55.8, 54.3, 29.6, 13C NMR (101 MHz, CDCl3): δ 206.3, 152.1, 141.9, 138.8, 138.3,
22.7, 21.2. IR (cm−1): 3258, 2923, 1696, 1605, 1463, 1387, 1367, 131.6, 129.2, 128.0, 127.0, 126.8, 122.1, 62.5, 57.4, 56.4, 29.6,
1293, 1204, 1059, 1012, 865. HRMS (ESI): [M + Na]+ calcd for: 22.9, 21.6. IR (cm−1): 3261, 2977, 2961, 2924, 1694, 1466, 1399,
C19H23NO3SNa 368.1296, Found: 368.1297.
1374, 1239, 1195, 1077, 1060, 1007, 849, 835, 717. HRMS (ESI):
[M + Na]+ calcd for: C21H23Br2NO2SNa 535.9693, Found:
3l: Pale yellow solid (296 mg, 82%). mp 193–194 °C. [α]D25
=
78.8 (c = 0.95, CHCl3). 1H NMR (400 MHz, CDCl3): δ 7.76 (d, J = 535.9695.
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3q: White solid (428 mg, 95%). mp 187–188 °C. [α]2D5 = 49.0 (t, J = 8.0 Hz,2H), 5.62 (s, 1H), 4.00 (d, J = 18.4 Hz, 1H), 3.95 (d,
(c = 0.99, CHCl3). 1H NMR (400 MHz, CDCl3): δ 7.78 (dd, J = J = 18.4 Hz, 1H), 1.78 (s, 3H), 1.31 (s, 9H). 13C NMR (101 MHz,
8.5, 5.3 Hz, 1H), 7.52 (d, J = 8.5 Hz, 2H), 7.38 (d, J = 8.6 Hz, CDCl3): δ 199.0, 154.6, 146.7, 136.6, 133.9, 128.8, 128.1, 126.0,
2H), 7.09 (td, J = 8.6, 1.9 Hz, 1H), 7.01 (d, J = 8.3 Hz, 1H), 6.13 123.8, 59.5, 56.3, 49.3, 29.3, 22.9. IR (cm−1): 3277, 2975, 2961,
(s, 1H), 3.20 (dd, J = 8.2, 4.4 Hz, 1H), 2.77 (dd, J = 18.2, 8.3 Hz, 2924, 1677, 1584, 1486, 1397, 1382, 1219, 1070, 1055, 1004,
1H), 2.50 (dd, J = 18.2, 4.3 Hz, 1H), 1.65 (s, 3H), 1.27 (s, 9H). 907, 823, 639. HRMS (ESI): [M + Na]+ calcd for: 521.9714,
13C NMR (101 MHz, CDCl3): δ 205.8, 167.6 (d, JFC = 258.2 Hz), Found: 521.9711.
4
5
156.5 (d, JFC = 10.3 Hz), 142.0, 133.5 (d, JFC = 1.6 Hz), 131.6,
129.2, 126.5 (d, 4JFC = 10.7 Hz), 122.1, 116.4 (d, 3JFC = 24.0 Hz),
113.1 (d, 3JFC = 22.4 Hz), 62.4, 57.1, 56.4, 29.8 (d, 5JFC = 1.9 Hz),
22.9, 21.5. 19F NMR (376 MHz, CDCl3): δ −100.78. IR (cm−1):
3263, 2976, 2965, 2928, 1689, 1613, 1590, 1481, 1400, 1271,
1244, 1084, 1057, 1007, 936, 852, 825, 794. HRMS (ESI): [M +
Na]+ calcd for: C21H23BrFNO2SNa 474.0515, Found: 474.0515.
3r: White solid (420 mg, 90%). mp 188–189 °C. [α]2D5 = 28.4
General procedure for deprotection
0.5 mmol 3g and 5 mL MeOH were placed in a 25 mL round-
bottom flask and then 1 mL aqueous HCl (36%) was added
dropwise with stirring at room temperature. Then a white solid
was produced and the reaction process was monitored by TLC.
After 2 h, the reaction was complete and the hydrochloride
solid 4 was filtered. The crude product was washed with
MeOH three times for purification.
1
(c = 1.01, CHCl3). H NMR (400 MHz, CDCl3): δ 7.69 (d, J = 8.1
4: White solid (153 mg, 92%). mp 192–193 °C. [α]2D5 = 101.1
Hz, 1H), 7.52 (d, J = 8.3 Hz, 2H), 7.41–7.32 (m, 4H), 6.08 (s,
1H), 3.19 (dd, J = 7.8, 4.2 Hz, 1H), 2.76 (dd, J = 18.1, 8.2 Hz,
1H), 2.49 (dd, J = 18.2, 3.8 Hz, 1H), 1.64 (s, 3H), 1.26 (s, 9H).
13C NMR (101 MHz, CDCl3): δ 206.3, 155.0, 142.3, 142.0, 135.5,
131.6, 129.2, 128.8, 126.7, 125.2, 122.1, 62.5, 57.0, 56.4, 29.7,
22.9, 21.6. IR (cm−1): 3256, 2983, 1701, 1597, 1399, 1323, 1201,
1067, 1053, 1008, 881, 833, 827, 789. HRMS (ESI): [M + Na]+
calcd for: C21H23BrClNO2SNa 490.0219, Found: 490.0220.
3s: White solid (477 mg, 93%). mp 201–203 °C. [α]2D5 = 19.7
1
(c = 0.68, MeOH). H NMR (400 MHz, DMSO): δ 9.01 (s, 3H),
7.71–7.60 (m, 4H), 7.53–7.32 (m, 4H), 3.72–3.65 (m, 1H),
3.07–2.97 (m, 1H), 2.83 (dd, J = 17.8, 4.4 Hz, 1H), 1.74 (s,
3H).13C NMR (101 MHz, DMSO): δ 204.7, 153.1, 139.6, 136.2,
135.6, 128.6, 128.3, 127.8, 126.8, 126.0, 123.3, 59.6, 53.6, 29.4,
20.8. IR (cm−1): 3069, 2923, 2861, 2813, 2745, 1703.9, 1603,
1575, 1504, 1288, 762, 701. HRMS (ESI): [M + Na]+ calcd for:
C17H17ClN2O3Na 355.0825, Found: 355.1276.
1
(c = 0.99, CHCl3). H NMR (400 MHz, CDCl3): δ 7.62 (d, J = 8.4
Reduction procedure
Hz, 1H), 7.55–7.50 (m, 4H), 7.37 (d, J = 8.3 Hz, 2H), 6.07 (s,
1H), 3.18 (dd, J = 7.6, 4.1 Hz, 1H), 2.76 (dd, J = 18.2, 8.2 Hz,
1H), 2.50 (dd, J = 18.2, 3.8 Hz, 1H), 1.64 (s, 3H), 1.26 (s, 9H).
13C NMR (101 MHz, CDCl3): δ 206.5, 155.1, 142.0, 135.9, 131.6,
131.2, 129.8, 129.2, 126.8, 125.3, 122.1, 62.5, 56.9, 56.4, 29.6,
22.9, 21.6. IR (cm−1): 3259, 2983, 2965, 1698, 1594, 1575, 1399,
1321, 1200, 1052, 1007, 870, 830, 826, 787. HRMS (ESI): [M +
Na]+ calcd for: C21H23Br2NO2SNa 535.9693, Found: 535.9692.
7a: Colourless oil (178 mg, 52%). [α]2D5 = −3.5 (c = 0.47,
A solution of 3a (710 mg, 0.2 mmol) in 3 mL of anhydrous
THF was cooled to −78 °C. Then, DIBAL (1.0 M in toluene,
0.6 mL, 0.6 mmol) was added dropwise and the mixture was
stirred at this temperature for 4 h. After completion of the reac-
tion, several drops of saturated ammonium chloride solution
were added and the mixture was allowed to come to room
temperature. The solvents were removed, and the residue was
dissolved in dichloromethane and extracted with brine. The
combined organic layers were dried over anhydrous Na2SO4
and concentrated in vacuo, and the crude mixture was charged
onto silica gel and purified by flash chromatography to
furnish the corresponding product 5 in 90% yield.
1
CHCl3). H NMR (400 MHz, CDCl3): δ 7.90 (d, J = 4.0 Hz, 2H),
7.52 (t, J = 8.0 Hz, 1H), 7.40 (t, J = 7.2 Hz, 4H), 7.29 (t, J = 8.0
Hz, 2H), 7.20 (t, J = 7.2 Hz, 1H), 5.73 (s, 1H), 3.91 (d, J = 16.0
Hz, 1H), 3.79 (d, J = 16.0 Hz, 1H), 1.78 (s, 3H), 1.30 (s, 9H). 13C
NMR (101 MHz, CDCl3): δ 199.4, 146.7, 137.2, 133.5, 128.6,
128.5, 128.1, 127.0, 125.1, 59.5, 56.0, 49.4, 29.4, 23.0.IR (cm−1):
3279, 2976, 2961, 2925, 1677, 1447, 1377, 1348, 1223, 1059,
761, 699, 690. HRMS (ESI): [M + Na]+ calcd for: 366.1504,
Found: 366.1502.
5: White solid (64 mg, 90%). mp 225–226 °C. [α]2D5 = 64.6
(c = 0.13, CHCl3). 1H NMR (400 MHz, CDCl3): δ 7.61–7.56
(m, 2H), 7.42–7.35 (m, 2H), 7.32–7.20 (m, 4H), 7.14 (t, J = 7.1
Hz, 1H), 6.13 (s, 1H), 4.77 (t, J = 5.1 Hz, 1H), 3.66 (dd, J = 16.1,
9.8 Hz, 1H), 2.97 (dd, J = 16.1, 7.6 Hz, 1H), 2.76 (ddd, J = 9.7,
7.6, 5.3 Hz, 1H), 2.54 (d, J = 5.3 Hz, 1H), 1.80 (s, 3H), 1.29 (s,
9H).13C NMR (101 MHz, CDCl3): δ 147.8, 143.8, 143.8, 128.8,
128.3, 126.7, 126.7, 125.7, 125.4, 124.1, 62.8, 56.2, 54.8, 31.8,
29.7, 26.9, 23.2. IR (cm−1): 3227, 2981, 2957, 2914, 1466, 1390,
1180, 1025, 1012, 960, 753, 734, 697. HRMS (ESI): [M + Na]+
calcd for: C21H27NO2SNa 380.1660, Found: 380.1657.
7b: Yellow oil (252 mg, 65%). [α]2D5 = −35.8 (c = 0.91, CHCl3).
1H NMR (400 MHz, CDCl3): δ8.15 (d, J = 8.0 Hz, 2H), 7.89 (d,
J = 8.0 Hz, 2H), 7.57 (d, J = 8.0 Hz, 3H), 7.43 (t, J = 8.0 Hz, 2H),
5.62 (s, 1H), 4.00 (d, J = 18.4 Hz, 1H), 3.95 (d, J = 18.4 Hz, 1H),
1.78 (s, 3H), 1.31 (s, 9H). 13C NMR (101 MHz, CDCl3): δ 199.0,
154.6, 146.7, 136.6, 133.9, 128.8, 128.1, 126.0, 123.8, 59.5, 56.3,
49.3, 29.3, 22.9. IR (cm−1): 3278, 2976, 2926, 1676, 1597, 1519,
1449, 1347, 1225, 1058, 856, 757, 700, 689. HRMS (ESI): [M +
Na]+ calcd for: 411.1354, Found: 411.1352.
Acknowledgements
7c: White solid (364 mg, 73%). Mp 59–60 °C. [α]2D5 = −41.3
1
(c = 0.77, CHCl3). H NMR (400 MHz, CDCl3): δ7.76 (d, J = 8.0 We gratefully acknowledge the financial support from the
Hz, 2H), 7.59 (d, J = 12.0 Hz, 2H), 7.57 (d, J = 8.0 Hz, 3H), 7.43 National Natural Science Foundation of China (no. 21102071)
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Paper
and the Fundamental Research Funds for the Central Univer-
sities (no. 1107020522 and 1082020502). The Jiangsu 333
program (for Pan) and the Changzhou Jin-Feng-Huang
program (for Han) are also acknowledged.
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