Synthesis of Amide Enol Carbamates and Carbonates through Cu(OTf)2-Catalyzed Reactions of Ynamides with t-Butyl Carbamates/Carbonates

Article abstract of DOI:10.1021/acs.joc.9b03512

A highly regioselective approach to access amide enol carbamates and carbonates 5a-5c′, 7a-7h, and 9 was developed through Cu(OTf)₂-catalyzed reactions of ynamides 4 with t-butyl carbamates 2 and 8 and t-butyl carbonates 6. Moreover, this strategy was successfully applied to generate amide enol carbamates 11a-11s and 14a-14f from imides 10 and 13 with ynamides through an N-Boc cleavage-addition ring-opening process. A range of substituents was amenable to this transformation, and the desired amide enol carbamates and carbonates were obtained in moderate to good yields.

Full text of DOI:10.1021/acs.joc.9b03512

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Article
Synthesis of Amide Enol Carbamates and Carbonates through Cu(OTf)2-
Catalyzed Reaction of Ynamides with t-Butyl Carbamates/Carbonates
Pan Han, Zhuo-Ya Mao, Ming Li, Chang-Mei Si, Bang-Guo Wei, and Guo-Qiang Lin
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b03512 • Publication Date (Web): 12 Mar 2020
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Synthesis of Amide Enol Carbamates and Carbonates through
Cu(OTf)2-Catalyzed Reaction of Ynamides with t-Butyl Carbamates/Carbonates
Pan Han,†, ‡ Zhuo-Ya Mao,† Ming Li,† Chang-Mei Si,*,† Bang-Guo Wei*,† and Guo-Qiang Lin§
† Department of Natural Medicine, School of Pharmacy, Fudan University, 826 Zhangheng Road,
Shanghai 201203, China
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‡ College of Chemistry and Chemical Engineering, China West Normal University, 1 Shida Road,
Nanchong 637002, China
§
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road,
Shanghai 200032, China
Abstract
R2
X
R4
N
EWG
R1 R2
X
R3
4a-4r
O
R3
R1
Boc
N
O
R4
: X=N
EWG
2a-m
: X=N
Cu(OTf)2
1
5a-5c'
6a-d 8
, : X=O, R =H
7a-h 9
, : X=O, R1=H
R4
H
OTBS
n
EWG
O
O
N
(1) RMgBr
4,
R3
N
O
R
N
O
(2) Cu(OTf)2
n
H
Boc
OTBS
(n=0)
10
n = 0
11a~11s
14a~14f
(n=1)
13
n = 1
A highly regioselective approach to access amide enol carbamates and carbonates
5a-5c’, 7a-7h and 9 was developed through Cu(OTf)2 catalyzed reactions of ynamides
4 with t-butyl carbamates 2, 8 and t-butyl carbonates 6. Moreover, this strategy was
successfully applied to generate amide enol carbamates 11a-11s and 14a-14f from
imide 10 and 13 with ynamides through a N-Boc cleavage-addition-ring opening
process. A range of substituents were amenable to this transformation and the desired
amide enol carbamates and carbonates were obtained in moderate to good yields.
Introduction
The discovery of an efficient reaction or versatile synthetic method for new chemical
bonds or new functional groups is one of the most challenging and fascinating tasks in
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organic chemistry,1 as it provides important new applications in pharmaceuticals and
biologically active compounds.2 Among them, the formation of enamides (1a) is one
of the most important reactions in organic chemistry owing to the wide occurrence in
depsipeptides,3 pharmaceuticals4 and important natural products.5 Enol esters (1b) are
also versatile intermediates in organic chemistry, which are not only frequently used
as mild acylation reagents,6 but also applied as substrates in polymerization,7
hydrogenation,8 cycloaddition,9 aldol-10 and Mannich-type reactions11 and
cross-coupling reactions.12 However, amide enolates (1c) are rarely present in
literature. To our best knowledge, very few approaches were reported to synthesize
amide enolates: through metal salt or acid catalyzed hydroacyloxylation of ynamides
with carboxylic acids (Figure 1),13,14 suffering from complicated operation process or
harsh reaction conditions.15
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O
O
N
O
N
O
O
amide enolates (1c)
enol esters (1b)
enamides (1a)
Figure 1. The structures of enamides, enol esters and amide enolates.
The transition metal-catalyzed addition of carboxylic acids to alkynes was an efficient
method for the preparation of enol esters.16,17 Ynamide, a kind of functionalized
alkyne, is wildly used in modern organic synthesis and many important
transformations due to the advantages of high regio- and stereoselectivity.18,19
Hydroacyloxylation of ynamides is an efficient method for the synthesis of
α-acyloxyenamides. For example, Lam and co-workers reported an efficient and
regioselective Pd(OAc)2 catalyzed addition between carboxylic acids and ynamides
(Figure 2, a).13 A catalyst-free addition was later established by Bi and co-workers
(Figure 2, b).14 Gillaizeau achieved 3-amino isocoumarin derivatives through
acid-catalyzed intramolecular hydroacyloxylation of ynamide by tert-butyl
carboxylate (Figure 2, c).20 In addition, Zhao applied α-acyloxy enamide
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intermediates, in situ generated from ynamides and carboxylic acids, in the synthesis
of amides and peptides without causing any racemization.21
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Enol carbamates have been recognized as integral structural motifs of pharmaceuticals
and agrochemicals22 and have also served as versatile synthons in organic
transformations.23 Very recently, we found that the carbonyl oxygen atom of Boc
group could attack ynamide-derived intermediates upon the cleavage of t-butyl-O
bond under Lewis acid conditions.24 The driving force of this novel transformation
intrigued us to investigate the potential of such nucleophilic addition directly onto the
triple bond of ynamides. Herein we present an efficient approach for the synthesis of
amide enol carbamates and carbonates from ynamides through Cu(OTf)2-catalyzed
hydroacyloxylation with t-butyl carbamates/carbonates (Figure 2, d).
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Pd(OAc)2 catalytic addition of carboxylic acids to ynamides (Lam)13
O
EWG
7
8
9
O
R
Pd(OAc)2
70oC
N
Ar
RCO2H
+
(a)
EWG
R1
N
R1 Ar
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Catalyst-free addition of carboxylic acids to ynamides (Bi)14
O
toluene,100oC
EWG
O
R
RCO2H
+
N
R2
or DCM 25oC
(b)
EWG
R1
N
R1 R2
Acid catalyzed intramolecular addition-cyclization (Gillaizeau )20
R1
N
R1
N
R2
R2
protonic acid
or AgOTf
O
O
(c)
Ot-Bu
n
O
n = 0, 1
This work
Cu(OTf)2 catalyzed intermolecular addition-cyclization (
)
R3
R1 R2
N
R2
O
O
N
N
EWG
R1
Boc
or
R4
EWG
R4
Cu(OTf)2
DCM, rt
R3
N
+
(d)
or
R5
R3
O
R5
O
O
Boc
or
N
EWG
R4
O
OTBS
O
R3
O
R2
N
(1) RMgBr
n
or
O
O
R1
N
(2) Ynamides
Cu(OTf)2
R
N
n
Boc
n = 0,1
H
OTBS
H
Figure 2. Hydroacyloxylation of ynamides.
Results and discussions
Our investigation commenced with the reaction of ynamide 4a with carbamate 2a
under Brønsted acid or Lewis acid-promoted conditions. Obviously, the addition
reaction did not take place in the absence of catalyst (Table 1, entry 1). The
subsequent trials with Brønsted acid TFA and TfOH also turned out to be fruitless
.
(Table 1, entries 2-3). When catalytic amount of BF3 Et2O was examined, ynamide 4a
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.
was almost recovered (Table 1, entry 4). However, stoichiometric BF3 Et2O could lead
to the desired product 5a in 34% yield (Table 1, entry 5). Lewis acid LiCl and ZnCl2
proved to be effectiveless, likely due to their poor solubility in DCM (Table 1, entries
6-7). Then we moved to screen different triflate salts owing to their stronger acidity
and better solubility in DCM. As shown in Table 1, all the examined
trifluoromethanesulfonates could catalyze this addition reaction (Table 1, entries
8-13), and Cu(OTf)2 afforded 5a in the highest yield of 84% (Table 1, entry 13).
Different solvents were also examined for the Cu(OTf)2 catalyzed process (entries
14-16). Both DCE and toluene led to significant drop in yield for the formation of 5a,
and THF failed to deliver the desired product. It is worth mentioning that
benzylcarbamate 3 was not suitable for this transformation (Table 1, entry 17).
Ynamide 4a was almost completely recovered when copper salts Cu(OAc)2, CuBr2,
CuCl, CuBr or CuI was used as catalyst (Table 1, entry 18). Moreover, the reaction on
a gram scale (5 mmol of 2a) was also performed to obtain the addition product 5a
with 83% yield (Table 1, entry 19).
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Table 1. Optimization of reaction conditions.
Ts
N
N
catalyst
solvent
Ph
N
+
N
P
O
O
Bn
Ts
2a (P=Boc)
3 (P=Cbz)
Bn Ph
4a
5a
Entrya
Catalyst
--
Solvent
DCM
DCM
DCM
DCM
DCM
DCM
DCM
T(oC)
Y (%)f
1
2
3
4
5b
6
7
rt
NR
NR
NR
trace
34
TFA
TfOH
rt
rt
.
BF3 Et2O
-78~rt
-78~rt
rt
.
BF3 Et2O
ZnCl2
LiCl
NR
NR
rt
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Zn(OTf)2
AgOTf
DCM
DCM
DCM
DCM
DCM
DCM
DCE
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
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9
62
10
11
12
13
14
15
16
17c
18d
19e
AgNTf2
Ce(OTf)3
Ni(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
CuX
75
71
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70
84
45
PhMe
THF
58
NR
trace
NR
83
DCM
DCM
DCM
Cu(OTf)2
a The reactions were performed with 2a (0.5 mmol), 4a (0.5 mmol) and catalyst (0.05
b
mmol) in dry solvent (2 mL) at assigned reaction temperature for 15 min-1 h.
1
.
c
d
mmol BF3 Et2O was used; The protecting group of pyrrolidine was Cbz; CuX =
e
Cu(OAc)2, CuBr2, CuCl, CuBr or CuI. The reactions were performed with 2a (5
mmol), 4a (5 mmol) and Cu(OTf)2 (0.5 mmol) in dry DCM (20 mL) at rt for 30 min.
f Isolated yield. NR = No reaction.
Next, we turned to investigate the scope and limitation of ynamides 4 with carbamates
2 for this novel Cu(OTf)2-catalyzed transformation . As shown in Scheme 1, various
N-Ts ynamides with benzyl, aryl, alkyl and allyl substituents could afford the desired
products in moderate to good yields (5a-5m). N-Ms ynamides also worked well to
give the desired products 5n-5p in moderate yields. The low yield for 5k was
probably caused by the steric hindrance of o-methoxy group (38%). It is worth
mentioning that aliphatic alkyl substituted ynamides could also produce the desired
5l-5o in moderate yields. As for the carbamate substrates 2, both α-substituent (2b)
and β-substituent (2c) at N-Boc pyrrolidine were tolerated, providing the
corresponding products 5r and 5s in 60% and 61% yields, respectively. Other N-Boc
substrates were also tested. Piperidine and morpholine derivatives 2d and 2e
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successfully produced the desired 5t and 5u in 85% and 65% yields, respectively.
Seven-membered hexamethyleneimine derived substrate 2f, as well as bicyclic
carbamates 2g and 2h, also smoothly generated the desired products 5v-5x in
moderate yields. Notably, non-cyclic secondary amine-derived carbamates were also
suitable for this transformation (42-82% yield), except for the reaction with very
hindered N-Boc diisopropylamide (5a´).
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Scheme 1. The reactions of ynamides with t-butyl carbamatesa,b
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R1 R2
N
EWG
R1 R2
N
Cu(OTf)2
O
O
R3
N
+
DCM, rt
R4
EWG
Boc
N
R4 R3
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2a-2m
4
5
N
R
N
O
O
N
O
O
O
Ts
N
Bn
Ts
O
N
R
Ts
N
Ph
5f
5g
5h
R=4-MeOC6H4-, 69%
R=4-MeC6H4-, 73%
R=4-FC6H4-,80%
Me
5a
5b
5c
5d
5e
R=Bn, 84%
R=Ph, 80%
R=Me, 90%
R=n-C4H9-, 80%
R=Allyl-, 82%
5m
77%
5i
R=4-BrC6H4-,85%
5j
R=4-ClC6H4-,78%
R=2-MeOC6H4-, 38%
R=n-C4H9-,62%
5k
5l
Cl
N
N
N
N
O
O
O
O
O
O
O
O
Ms
Ms
Ms
O2S
N
N
N
N
Bn
Bn
Bn
Ph
85%
Bn Ph
5q
74%
5p
5n
74%
5o
77%
OTHP
X
COOBn
N
N
N
N
N
O
O
O
O
O
O
O
O
Ts
Ts
Ts
N
Ts
N
N
Bn Ph
Bn Ph
Bn Ph
Bn Ph
61%
5r
60%
H
5t
5u
X = CH2, 85%
X = O, 65%
5s
5v
76%
R1 R2
N
COOBn
N
O
O
H
O
N
Ts
O
N
Ts
O
O
Bn Ph
N
1
2
Ts
5y
5z
5a'
5b'
5c'
R = R = Ethyl-, 82%
R = R = n-Propyl-, 81%
R = R = i-Propyl-, 0%
R = Bn, R = Me, 74%
Bn
Ph
N
1
2
Bn Ph
1
2
1
2
5w
77%
5x
70%
1
2
R = R = Bn, 42%
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aThe reactions were performed with t-butyl carbamates 2 (0.5 mmol), ynamides 4 (0.5 mmol) and
5
6
Cu(OTf)2 (0.05 mmol) in dry DCM (2 mL) at rt for 15 min-1 h. b Isolated yield.
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8
9
Amide enol allyl carbonates, an important synthetic intermediates which have been
prepared by Stoltz and his collaborators through two complicated process in 2017.15b
Based on our above results, we continued to investigate the potential use of t-butyl
carbonates in this Cu(OTf)2-catalyzed process, and the results are summarized in
Scheme 2. The allylic carbonates 6a-c could react with different ynamides, producing
the desired products 7a-7g in moderate yields. Furthermore, the propargyl carbonate
6d could afford the desired amide enol carbonate 7h in 61% yield.
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Scheme 2. The reactions of ynamides with t-butyl carbonatesa,b
R
O
N
R
O
Cu(OTf)2
DCM, rt
EWG
O
R1
N
+
O
O
R2
O
EWG
R2 R1
6a-6d
4
7a-7h
R
O
O
O
N
O
N
O
O
O
O
O
Ts
Ts
N
R
Ms
Ph
Bn Ph
Bn Ph
7a R = Bn, 82%
7b R = Me, 58%
7c R = Allyl-, 77%
7f R = 1-methylallyl-, 54%
7g R = 3-phenylallyl-, 71%
7e 79%
7h R = propynyl-, 61%
7d R = n-C4H9-, 35%
a
The reactions were performed with t-butyl carbonates 6 (0.5 mmol), ynamide 4 (0.5 mmol) and
Cu(OTf)2 (0.05 mmol) in dry DCM (2 mL) at rt for 15 min-1 h. b Isolated yield.
This transformation could be extended to N,O-acetals. Compound 8, an unstable
carbamate intermediate prepared according to our previous process,25 successfully
reacted with ynamide 4r without destroying the N,O-acetal skeleton (Scheme 3), and
structure of the desired amide enol carbamate 9 was unambiguously confirmed by
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X-ray crystallographic analysis (see Supporting Information).
5
6
7
8
Scheme 3. The reaction of N,O-acetal 8 with ynamide 4r.
9
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Br
HN
O
O
O
Cu(OTf)2
+
O
NH
Ts
DCM
38%
N
Boc
Bn
N
Bn
Ts
Br
9
4r
8
Furthermore, we extended the method to imide substrates (10 and 13) to afford the
corresponding amide enol carbamates via two steps. The intermediates from addition
of Grignard reagent to imide reacted with ynamides were catalyzed by Cu(OTf)2 to
obtain amide enol carbamates (Schemes 4 and 5). Various addition products of
pyrrolidine imide 10 with different Grignard reagent were surveyed under the optimal
conditions. All proceeded smoothly to give the desired products in moderate yields
(11a-11s), with their structures unambiguously determined by X-ray crystallographic
analysis of the desilylation product 12 from compound 11a (see Supporting
Information). As for the piperidine imide 13 which reacted with Grignard reagent
to give intermediates bearing either an aryl (13a-d) or aliphatic (13e-f)
substituent could also lead to the desired keto products 14a-f in moderated
yields.
Scheme 4. The reactions of pyrrolidine imide with ynamidesa, b.
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R4
OTBS
O
EWG
OTBS
O
O
N
(1) RMgBr, THF, -78 oC
R3
N
H
O
o
R
N
4
(2) , Cu(OTf)2, DCM, 0 C-rt
7
8
9
Boc
10
11
10
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R
Me
Ts
OTBS
O
N
Me
Ts
OTBS
O
N
N
O
H
Ph
O
OMe
N
H
O
O
11a
11c
11e
11b
11d
11f
R = H, 84%
R = F, 68%
11g
72%
R = Me, 78%
R = MeO, 76%
R = Ph, 76%
-t
R = Bu , 46%
Me
Ts
Me
Ts
OTBS
O
N
N
OTBS
O
O
N
Ph
Ph
Ph
N
H
O
N
O
H
OMe
S
O
11h
42%
11i
69%
Me
Ts
Ts Bn
N
R
OTBS
O
O
OTBS
Ph
O
N
H
O
N
H
O
O
11j
0%
11k
11m
11o
R = H, 60%
11l
R = Cl, 55%
R = Me, 72%
R = OMe, 62%
Ts Bn
11n
R = Br, 60%
Ts Bn
N
OTBS
Ph
O
OTBS
Ph
O
N
N
O
N
O
H
H
O
Cl
O
MeO
11q
64%
11p
56%
Ts Ph
Bn
p-ClC6H4O2S
OTBS
Ph
O
N
OTBS
Ph
O
N
Ph
Ph
N
O
N
O
H
H
O
O
11r
, 65%
11s
, 59%
aReaction conditions: (1) 10 (1.0 mmol) and RMgBr (2.0 mmol) in dry THF (10 mL) at -78 oC for
1.5 h; (2) The crude product, ynamide 4 (0.5 mmol) and Cu(OTf)2 (0.05 mmol) in dry DCM (2
mL) at 0 oC - rt for 15 min-1 h. b Isolated yield.
Scheme 5. The reactions of piperidine imide with ynamidesa, b.
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5
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7
8
9
OTBS
O
Bn
Ts
(1) RMgBr, THF, -78 oC
N
O
O
Ph
o
N
4
R
(2) , Cu(OTf)2, DCM, 0 C-rt
N
H
O
Boc
13
OTBS
14
10
11
12
13
14
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17
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Bn
O
Ts
Bn
Ts
O
O
N
O
O
N
N
Ph
Ph
N
N
O
H
H
OTBS
OTBS
F
14b
14d
14a
62%
52%
74%
Bn
O
Ts
O
Ts
Ts
Bn
O
N
O
O
Ph
Ph
Ph
O
N
N
H
OTBS
69%
H
OTBS
OMe
Me
14c
Bn
O
Bn
O
Ts
O
O
O
N
O
N
Ph
N
H
N
H
OTBS
OTBS
14e
66%
14f
72%
aReaction conditions: (1) 13 (1.0 mmol) and RMgBr (2.0 mmol) in dry THF (10 mL) at -78 oC for
1.5 h; (2) The crude product, ynamide 4 (0.5 mmol) and Cu(OTf)2 (0.05 mmol) in dry DCM (2
mL) at 0 oC - rt for 15 min-1 h. b Isolated yield.
On the basis of our obtained experimental results and the precedent ynamide
chemistrys,24,26 a possible mechanism for this Cu(OTf)2-catalyzed transformation was
illustrated in Figure 3. First, the triple bond in ynamide 4 was activated by copper (II)
triflate. The resulting vinyl Cu(II) intermediate int-1 was subsequently attacked by
carbamates/carbonates through the cleavage of t-butyl group to give int-2, which was
finally hydrolyzed to generate the desired amide enol carbamates/carbonates.
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5
R1
O
Cu(OTf)2
EWG
R2
EWG
R1
N
6
7
8
X
O
N
R2
4
9
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EWG
R2
TfOCu
O
R1
R1
N
t-Bu
O
O
EWG
Cu
X
O
N
R2
TfO
OTf
X
int-2
EWG
TfOCu
R1
•
N
R2
int-1
Figure 3. The proposed reaction mechanism
Conclusion
In summary, we established a highly regioselective approach for the synthesis of
amide enol carbamates 5. The reaction went through a Cu(OTf)2-catalyzed process
from ynamides 4 and t-butyl carbamates 2. Moreover, t-butyl carbonates 6a-d could
also react with ynamides 4 to give amide enol carbonates 7a-7h under mild reaction
conditions. It is worth mentioning that amide enol carbamates 11a-11s and 14a-14f
were successfully synthesized through this Cu(OTf)2-catalyzed strategy from
N,O-acetals 10 and 13.
Experimental Section
I General Methods
THF was distilled from sodium/benzophenone, and DCM was distilled from
phosphorus pentoxide. Reactions were monitored by TLC-FID. Flash chromatography
was performed on silica gel (300−400 mesh) with petroleum/EtOAc as the eluent.
HRMS was conducted on a Thermo Scientific LTQ Orbitrap XL apparatus. IR spectra
were measured using a film on a Fourier transform infrared spectrometer. NMR
spectra were recorded at 400 MHz, and chemical shifts are reported in δ (ppm)
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referenced to an internal TMS standard for H NMR and CDCl3 (77.16 ppm) for
5
6
7
8
13C{1H} NMR. The heat source was an oil bath.
II Experimental
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General Procedure for Synthesis of N-Boc amides 2.27
To a solution of DMAP (0.25 mmol), amine (5 mmol) in DCM (10 mL) was slowly
added Boc2O (5.5 mmol) at rt. After stirring for 1 h, the mixture was concentrated in
vacuo and the resides was purified by flash chromatography to give pure N-Boc
amides.
General Procedure for Synthesis of O-Boc esters 6.28
To a solution of DMAP (0.25 mmol), alcohol (10 mmol) in DCM (10 mL) was slowly
added Boc2O (5 mmol) at rt. After stirring for 1 h, the mixture was concentrated in
vacuo and the residue was purified by flash chromatography to give pure O-Boc
esters.
General Procedure for Synthesis of ynamide 4. 29
To a mixture of an amide (2 mmol), K3PO4 (4 mmol), CuSO4•5H2O (0.2mmol,) and
1,10-phenanthroline (0.4 mmol,) in toluene at N2 atmosphere was added a solution
1-bromoalkyne (2.2 mmol) in toluene. The reaction was stirred at 75 oC for 24 h at N2
atmosphere. The reaction mixture was cooled to room temperature and diluted with
EtOAc and filtered through Celite and the filtrate was concentrated in vacuo. The
crude products were purified by silica gel flash chromatography to afford the desired
ynamide.
General Procedure for Synthesis of 5, 7 and 9.
To a solution of N-Boc amides 2 or O-Boc esters 6 (0.5 mmol) and ynamides 4 (0.5
mmol) in dry DCM (2 mL) was added Cu(OTf)2 (18 mg, 0.05 mmol) at rt. After
stirring for 15 min to 1 h, the reaction mixture was quenched with aqueous NaHCO3.
Extracted with DCM (10 ml × 3), and the combined organic layers were washed with
brine. Dried, filtered, and concentrated, the residue was purified by flash
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chromatography on silica gel.
5
6
7
Procedure for synthesis of 5a (5 mmol scale)
8
9
To a solution of N-Boc amide 2a (856 mg, 5 mmol) and ynamide 4a (1.81 g, 5 mmol)
in dry DCM (20 mL) was added Cu(OTf)2 (180 mg, 0.5 mmol) at rt. After stirring for
30 min, the reaction mixture was quenched with aqueous NaHCO3. Extracted with
DCM (30 mL × 3), and the combined organic layers were washed with brine. Dried,
filtered, and concentrated, the residue was purified by flash chromatography on silica
gel (PE/EtOAc = 4/1) to give colorless oil 5a (1.98 g, 83%).
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(E)-1-((N-benzyl-4-methylphenyl)sulfonamido)-2-phenylvinyl
pyrrolidine-1-carboxylate (5a). Colorless oil (200 mg, 84%); purified by column
chromatography on silica gel (PE/EtOAc = 4/1); IR (film): νmax 3062, 3029, 2974,
2877, 1727, 1404, 1355, 1164, 1065, 816, 710, 658 cm-1; 1H NMR (400 MHz, CDCl3)
δ 7.77 (d, J = 8.0 Hz, 2H), 7.31-7.21 (m, 6H), 7.15-7.09 (m, 6H), 6.34 (s, 1H), 4.47 (s,
2H), 3.36 (t, J = 6.0 Hz, 2H), 2.98 (t, J = 6.8 Hz, 2H), 2.41 (s, 3H), 1.86-1.77 (m, 4H)
13
ppm; C{1H} NMR (100 MHz, CDCl3) δ 152.1, 143.7, 137.3, 137.1, 134.9, 132.5,
129.9, 129.4, 128.7, 128.2, 128.1, 128.0, 127.9, 127.7, 122.5, 52.7, 46.5, 46.0, 25.7,
24.9, 21.6 ppm; HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for C27H29N2O4S,
477.1843; found, 477.1847.
(E)-1-((4-methyl-N-phenylphenyl)sulfonamido)-2-phenylvinyl
pyrrolidine-1-carboxylate (5b). Pale yellow solid (185 mg, 80%), purified by column
chromatography on silica gel (PE/EtOAc = 4/1); mp 118-120 oC; IR (film): νmax 3061,
1
2976, 2878, 1731, 1403, 1360, 1167, 1111, 693 cm-1; H NMR (400 MHz, CDCl3) δ
7.60-7.54 (m, 4H), 7.32-7.26 (m, 4H), 7.25-7.18 (m, 5H), 7.17 (s, 1H), 6.48 (s, 1H),
3.42 (t, J = 6.8 Hz, 2H), 3.13 (t, J = 6.8 Hz, 2H), 2.39 (s, 3H), 1.89-1.82 (m, 4H) ppm;
13C{1H} NMR (100 MHz, CDCl3) δ 151.5, 143.9, 139.5, 139.2, 137.1, 132.7, 129.2,
129.0, 128.9, 128.3, 128.2, 127.9, 127.6, 126.8, 120.6, 46.6, 46.2, 25.8, 25.0, 21.7
ppm; HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for C26H27N2O4S, 463.1686; found,
463.1690.
(E)-1-((N,4-dimethylphenyl)sulfonamido)-2-phenylvinyl
pyrrolidine-1-carboxylate (5c). White solid (180 mg, 90%), purified by column
o
chromatography on silica gel (PE/EtOAc = 4/1); mp 97-99 C; IR (film): νmax 3057,
1
2975, 2878, 1724, 1408, 1354, 1158, 1067, 694 cm-1; H NMR (400 MHz, CDCl3) δ
7.76 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 7.2 Hz, 2H), 7.36-7.31 (m, 2H), 7.29-7.25 (m,
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3H), 6.20 (s, 1H), 3.20-3.15 (m, 4H), 3.10 (s, 3H), 2.42 (s, 3H), 1.84-1.78 (m, 4H)
5
6
13
ppm; C{1H} NMR (100 MHz, CDCl3) δ 152.3, 143.6, 140.4, 136.9, 132.4, 129.4,
7
8
9
128.6, 128.5, 128.0, 127.6, 118.1, 46.3, 46.2, 36.9, 25.7, 24.9, 21.6 ppm; HRMS
(ESI-Orbitrap) m/z: [M + H]+ calcd for C21H25N2O4S, 401.1530; found, 401.1533.
(E)-1-((N-butyl-4-methylphenyl)sulfonamido)-2-phenylvinyl
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pyrrolidine-1-carboxylate (5d). Foam solid (177 mg, 80%); purified by column
chromatography on silica gel (PE/EtOAc = 4/1); IR (film): νmax 3056, 2958, 2874,
1
1728, 1405, 1355, 1166, 1065, 693 cm-1; H NMR (400 MHz, CDCl3) δ 7.80 (d, J =
8.4 Hz, 2H), 7.63 (d, J = 7.6 Hz, 2H), 7.34-7.24 (m, 5H), 6.44 (s, 1H), 3.34 (t, J = 6.8
Hz, 2H), 3.27 (t, J = 7.6 Hz, 2H), 2.94 (t, J = 6.4 Hz, 2H), 2.41 (s, 3H), 1.86-1.76 (m,
13
4H), 1.60-1.52 (m, 2H), 1.25-1.15 (m, 2H), 0.77 (t, J = 7.2 Hz, 3H) ppm; C{1H}
NMR (100 MHz, CDCl3) δ 152.1, 143.6, 137.4, 136.9, 132.8, 129.4, 129.1, 128.3,
128.2, 128.0, 122.5, 48.8, 46.5, 45.9, 30.0, 25.7, 24.9, 21.6, 20.2, 13.6 ppm; HRMS
(ESI-Orbitrap) m/z: [M + H]+ calcd for C24H31N2O4S, 443.1999; found, 443.2001.
(E)-1-((N-allyl-4-methylphenyl)sulfonamido)-2-phenylvinyl
pyrrolidine-1-carboxylate (5e). White solid (175 mg, 82%), purified by column
chromatography on silica gel (PE/EtOAc = 4/1); mp 102-103 oC; IR (film): νmax 3057,
1
3025, 2976, 2877, 1728, 1404, 1356, 1165, 1065, 663 cm-1; H NMR (400 MHz,
CDCl3) δ 7.78 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 7.2 Hz, 2H), 7.32-7.22 (m, 5H), 6.40
(s, 1H), 5.86-5.75 (m, 1H), 5.16-5.10 (m, 1H), 5.05-5.01 (m, 1H), 3.99 (d, J = 6.8 Hz,
2H), 3.32 (t, J = 6.8 Hz, 2H), 3.02 (t, J = 6.8 Hz, 2H), 2.41 (s, 3H), 1.84-1.78 (m, 4H)
13
ppm; C{1H} NMR (100 MHz, CDCl3) δ 151.9, 143.7, 138.0, 137.1, 132.8, 132.4,
129.4, 128.9, 128.4, 128.2, 128.0, 121.2, 119.4, 52.6, 46.4, 46.0, 25.7, 24.9, 21.6 ppm;
HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for C23H27N2O4S, 427.1686; found,
427.1692.
(E)-1-((N-benzyl-4-methylphenyl)sulfonamido)-2-(4-methoxyphenyl)vinyl
pyrrolidine-1-carboxylate (5f). Foam solid (175 mg, 69%); purified by column
chromatography on silica gel (PE/EtOAc = 2/1); IR (film): νmax 33032, 2955, 2878,
2837, 1725, 1607, 1161, 737 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 7.2 Hz,
2H), 7.48 (d, J = 8.0 Hz, 2H), 7.35-7.26 (m, 5H), 7.08 (d, J = 8.0 Hz, 2H), 6.76 (d, J =
8.0 Hz, 2H), 5.52 (s, 1H), 4.82 (s, 2H), 3.75 (s, 3H), 3.26-3.20 (m, 4H), 2.43 (s, 3H),
1.87-1.79 (m, 4H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 159.3, 151.3, 143.4,
137.8, 137.1, 136.7, 129.9, 129.6, 129.4, 128.4, 127.8, 127.7, 125.8, 120.6, 113.8,
55.3, 53.9, 46.4, 46.3, 25.8, 24.9, 21.6 ppm; HRMS (ESI-Orbitrap) m/z: [M + H]+
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calcd for C28H31N2O5S, 507.1948; found, 507.1952.
5
6
(E)-1-((N-benzyl-4-methylphenyl)sulfonamido)-2-(p-tolyl)vinyl
7
8
9
pyrrolidine-1-carboxylate (5g). White solid (179 mg, 73%), purified by column
chromatography on silica gel (PE/EtOAc = 4/1); mp 127-129 oC; IR (film): νmax 3060,
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1
2978, 2920, 2880, 1724, 1407, 1354, 1164, 1069, 736 cm-1; H NMR (400 MHz,
CDCl3) δ 7.77 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 7.2 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H),
7.17-7.10 (m, 5H), 6.93 (d, J = 8.0 H, 2H), 6.30 (s, 1H), 4.47 (s, 2H), 3.34 (t, J = 6.4
Hz, 2H), 2.98 (t, J = 6.4 Hz, 2H), 2.41 (s, 3H), 2.27 (s, 3H), 1.86-1.75 (m, 4H) ppm;
13C{1H} NMR (100 MHz, CDCl3) δ 152.2, 143.7, 137.6, 137.3, 136.8, 135.1, 129.9,
129.6, 129.4, 128.8, 128.6, 128.2, 128.1, 127.9, 122.5, 52.7, 46.5, 46.0, 25.7, 24.9,
21.6, 21.3 ppm; HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for C28H31N2O4S,
491.1999; found, 491.2006.
(E)-1-((N-benzyl-4-methylphenyl)sulfonamido)-2-(4-fluorophenyl)vinyl
pyrrolidine-1-carboxylate (5h). White solid (198 mg, 80%), purified by column
chromatography on silica gel (PE/EtOAc = 4/1); mp 160-162 oC; IR (film): νmax 3033,
2975, 2878, 1726, 1405, 1352, 1163, 1068, 658 cm-1; H NMR (400 MHz, CDCl3) δ
1
7.79 (d, J = 7.6 Hz, 2H), 7.31-7.25 (m, 4H), 7.22-7.17 (m, 2H), 7.16-7.10 (m, 3H),
6.78 (t, J = 8.4 Hz, 2H), 6.30 (s, 1H), 4.45 (s, 2H), 3.35 (t, J = 6.0 Hz, 2H), 2.96 (t, J =
6.4 Hz, 2H), 2.42 (s, 3H), 1.86-1.77 (m, 4H) ppm; 13C{1H} NMR (100 MHz, CDCl3)
δ 162.3 (d, J = 245.8 Hz, 1C), 152.0, 143.9, 137.0, 136.9, 134.8, 130.4, 130.3, 129.9,
129.5, 128.6, 128.5, 128.2, 128.1, 121.9, 115.0, 114.8, 52.5, 46.5, 46.0, 25.7, 24.9,
21.6 ppm; HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for C27H28FN2O4S, 495.1748;
found, 495.1757.
(E)-1-((N-benzyl-4-methylphenyl)sulfonamido)-2-(4-bromophenyl)vinyl
pyrrolidine-1-carboxylate (5i). White solid (236 mg, 85%), purified by column
chromatography on silica gel (PE/EtOAc = 4/1); mp 148-149 oC; IR (film): νmax 3032,
2974, 2878, 1728, 1404, 1355, 1164, 1071, 660 cm-1; H NMR (400 MHz, CDCl3) δ
1
7.78 (d, J = 7.6 Hz, 2H), 7.30-7.24 (m, 4H), 7.23-7.18 (m, 2H), 7.18-7.11 (m, 3H),
7.05 (d, J = 8.0 Hz, 2H), 6.28 (s, 1H), 4.46 (s, 2H), 3.36 (t, J = 6.4 Hz, 2H), 2.98 (t, J
= 6.8 Hz, 2H), 2.43 (s, 3H), 1.87-1.78 (m, 4H) ppm; 13C{1H} NMR (100 MHz,
CDCl3) δ 151.9, 143.9, 137.7, 137.0, 134.7, 131.6, 131.1, 130.2, 130.0, 129.5, 128.3,
128.2, 128.1, 121.7, 52.5, 46.5, 46.0, 25.7, 24.9, 21.7 ppm; HRMS (ESI-Orbitrap)
m/z: [M + H]+ calcd for C27H28BrN2O4S, 555.0948; found, 555.0955.
(E)-1-(N-benzylmethylsulfonamido)-2-(4-chlorophenyl)vinyl
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pyrrolidine-1-carboxylate (5j). White solid (170 mg, 78%), purified by column
chromatography on silica gel (PE/EtOAc = 4/1); mp 126-127 oC; IR (film): νmax 3064,
3032, 2976, 2879, 1726, 1405, 1348, 1157, 1067, 732, 708 cm-1; 1H NMR (400 MHz,
CDCl3) δ 7.41-7.37 (m, 2H), 7.23-7.19 (m, 5H), 7.16-7.11 (m, 2H), 6.33 (s, 1H), 4.52
(s, 2H), 3.49 (t, J = 6.8 Hz, 2H), 3.39 (t, J = 6.8 Hz, 2H), 2.90 (s, 3H), 1.96-1.91 (m,
4H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 152.1, 138.7, 134.8, 133.7, 131.0,
130.1, 129.8, 128.5, 128.4, 128.3, 120.3, 53.0, 46.8, 46.5, 41.1, 25.8, 25.0 ppm;
HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for C21H24ClN2O4S, 435.1140; found,
435.1147.
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(E)-1-((N-benzyl-4-methylphenyl)sulfonamido)-2-(2-methoxyphenyl)vinyl
pyrrolidine-1-carboxylate (5k). Foam solid (96 mg, 38%); purified by column
chromatography on silica gel (PE/EtOAc = 2/1); IR (film): νmax 3064, 2953, 2878,
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1726, 1405, 1352, 1163, 1068, 658 cm-1; H NMR (400 MHz, CDCl3) δ 7.74 (d, J =
8.4 Hz, 2H), 7.44 (dd, J = 7.6, 1.2 Hz, 1H), 7.27-7.24 (m, 2H), 7.22 (d, J = 8.0 Hz,
2H), 7.15-7.06 (m, 4H), 6.72 (t, J = 7.6 Hz, 1H), 6.64 (d, J = 7.6 Hz, 1H), 6.57 (s,
1H), 4.47 (s, 2H), 3.66 (s, 3H), 3.34 (t, J = 6.8 Hz, 2H), 3.03 (t, J = 6.8 Hz, 2H), 2.40
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(s, 3H), 1.85-1.78 (m, 4H) ppm; C{1H} NMR (100 MHz, CDCl3) δ 156.8, 152.2,
143.5, 137.5, 137.4, 135.1, 129.9, 129.3, 129.1, 129.0, 128.1, 128.0, 127.7, 121.6,
120.3, 116.9, 110.2, 55.5, 53.0, 46.4, 46.0, 25.7, 25.0, 21.6 ppm; HRMS
(ESI-Orbitrap) m/z: [M + H]+ calcd for C28H31N2O5S, 507.1948; found, 507.1952.
(E)-1-((N-benzyl-4-methylphenyl)sulfonamido)hex-1-en-1-yl
pyrrolidine-1-carboxylate (5l). This compound was obtained in 92% purity as judged
by NMR analysis. White solid (142 mg, 62%), purified by column chromatography
on silica gel (PE/EtOAc = 5/1); mp 83-84 oC; IR (film): νmax 3031, 2955, 2928, 2873,
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1727, 1404, 1353, 1164, 1085, 659 cm-1; H NMR (400 MHz, CDCl3) δ 7.81 (d, J =
8.4 Hz, 2H), 7.46-7.41 (m, 2H), 7.32-7.26 (m, 5H), 5.38 (t, J = 7.6 Hz, 1H), 4.42 (s,
2H), 3.31 (t, J = 6.4 Hz, 2H), 2.92 (t, J = 6.4 Hz, 2H), 2.42 (s, 3H), 1.82-1.73 (m, 6H),
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1.06-0.98 (m, 2H), 0.94-0.84 (m, 2H), 0.72 (t, J = 6.8 Hz, 3H) ppm; C{1H} NMR
(100 MHz, CDCl3) δ 152.4, 143.5, 137.6, 136.0, 135.8, 129.9, 129.5, 128.4, 128.0,
127.9, 125.3, 51.7, 46.4, 45.9, 30.9, 27.0, 25.7, 24.9, 22.4, 21.6, 13.9 ppm; HRMS
(ESI-Orbitrap) m/z: [M + H]+ calcd for C25H33N2O4S, 457.2156; found, 457.2164.
(E)-1-((N,4-dimethylphenyl)sulfonamido)hex-1-en-1-yl
pyrrolidine-1-carboxylate (5m). This compound was obtained in 89% purity as judged
by NMR analysis. Colorless oil (146 mg, 77%); purified by column chromatography
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on silica gel (PE/EtOAc = 5/1); IR (film): νmax 2955, 2930, 2874, 1725, 1407, 1354,
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1167, 1085, 711, 695 cm-1; H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.4 Hz, 2H),
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7.29 (d, J = 8.0 Hz, 2H), 5.31 (t, J = 7.6 Hz, 1H), 3.29-3.24 (m, 2H), 3.06 (s, 3H),
3.06-3.03 (m, 2H), 2.42 (s, 3H), 2.11-2.04 (m, 2H), 1.82-1.77 (m, 4H), 1.38-1.26 (m,
4H), 0.88 (t, J = 6.8 Hz, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 152.8, 143.5,
139.6, 136.5, 129.4, 127.8, 121.4, 46.3, 46.0, 36.9, 31.1, 26.4, 25.7, 24.9, 22.4, 21.6,
14.0 ppm; HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for C19H29N2O4S, 381.1843;
found, 381.1849.
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(E)-1-(N-benzylmethylsulfonamido)hex-1-en-1-yl
pyrrolidine-1-carboxylate
(5n). White solid (141mg, 74%), purified by column chromatography on silica gel
(PE/EtOAc = 5/1); mp 62-64 oC; IR (film): νmax 3035, 2955, 2930, 2873, 1714, 1642,
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1342, 1083, 755 cm-1; H NMR (400 MHz, CDCl3) δ 7.50-7.46 (m, 2H), 7.35-7.28
(m, 3H), 5.38 (t, J = 7.6 Hz, 1H), 4.50 (s, 2H), 3.45 (t, J = 6.4 Hz, 2H), 3.39 (t, J = 6.8
Hz, 2H), 3.00 (s, 3H), 1.97-1.89 (m, 4H), 1.84-1.77 (m, 2H), 1.10-1.02 (m, 2H),
1.00-0.91 (m, 2H), 0.74 (t, J = 7.2 Hz, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ
152.9, 136.5, 135.9, 129.9, 128.5, 128.1, 124.9, 51.8, 46.7, 46.4, 40.2, 30.9, 27.1,
25.9, 25.0, 22.4, 13.9 ppm; HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for
C19H29N2O4S, 381.1843; found, 381.1849.
(E)-1-(N-benzylmethylsulfonamido)-2-cyclopropylvinyl
pyrrolidine-1-carboxylate (5o). White solid (140 mg, 77%), purified by column
o
chromatography on silica gel (PE/EtOAc = 5/1); mp 71-73 C; IR (film): νmax 3064,
3006, 2976, 2878, 1722, 1408, 1343, 1155, 1075, 757, 703 cm-1; 1H NMR (400 MHz,
CDCl3, rotamers) δ 7.53 (d, J = 6.8 Hz, 1.48H), 7.43 (d, J = 6.8 Hz, 0.52H), 7.35-7.27
(m, 3H), 4.84 (d, J = 10.0 Hz, 0.74H), 4.66 (s, 0.52H), 4.60 (s, 1.48H), 4.47 (d, J =
9.6 Hz, 0.26H), 3.48-3.40 (m, 2.96H), 3.38-3.33 (m, 1.04H), 3.03 (s, 2.24H), 3.02 (s,
0.76H), 1.94-1.87 (m, 4H), 1.36-1.28 (m, 0.26H), 1.26-1.17 (m, 0.74H), 0.76-0.70 (m,
0.52H), 0.55-0.48 (m, 1.48H), 0.33-0.27 (m, 0.52H), 0.27-0.21 (m, 1.48H) ppm;
13C{1H} NMR (100 MHz, CDCl3, rotamers) δ 152.9 (152.3), 136.3 (136.7), 136.1
(136.8), 130.0, 129.4, 128.9, 128.45, 128.40 (127.9), 128.1 (126.4), 52.2 (52.1), 46.6
(46.5), 46.4, 40.6 (40.3), 25.8 (25.9), 25.00 (25.04), 9.6 (8.7), 7.0, 6.7 ppm; HRMS
(ESI-Orbitrap) m/z: [M + H]+ calcd for C18H25N2O4S, 365.1530; found, 365.1533.
(E)-1-(N-benzylmethylsulfonamido)-2-phenylvinyl
pyrrolidine-1-carboxylate
(5p). White solid (170 mg, 85%), purified by column chromatography on silica gel
(PE/EtOAc = 4/1); mp 91-93 oC; IR (film): νmax 2976, 2879, 1724, 1405, 1348, 1155,
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1065, 696 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.44-7.40 (m, 2H), 7.36-7.32 (m, 2H),
7.25-7.18 (m, 6H), 6.38 (s, 1H), 4.55 (s, 2H), 3.47 (t, J = 6.8 Hz, 2H), 3.36 (t, J = 6.8
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Hz, 2H), 2.83 (s, 3H), 1.94-1.89 (m, 4H) ppm; C{1H} NMR (100 MHz, CDCl3) δ
152.2, 138.7, 135.2, 132.5, 130.1, 128.6, 128.5, 128.4, 128.3, 128.0, 120.9, 53.2, 46.8,
46.4, 41.4, 25.8, 25.0 ppm; HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for
C21H25N2O4S, 401.1530; found, 401.1532.
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(E)-1-((N-benzyl-4-chlorophenyl)sulfonamido)-2-phenylvinyl
pyrrolidine-1-carboxylate (5q). White solid (184 mg, 74%), purified by column
chromatography on silica gel (PE/EtOAc = 4/1); mp 128-129 oC; IR (film): νmax 3063,
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2975, 2878, 1728, 1404, 1359, 1167, 1084, 754, 634 cm-1; H NMR (400 MHz,
CDCl3) δ 7.79-7.74 (m, 2H), 7.40-7.35 (m, 2H), 7.33-7.29 (m, 2H), 7.21-7.11 (m,
8H), 6.35 (s, 1H), 4.52 (s, 2H), 3.36 (t, J = 6.8 Hz, 2H), 3.00 (t, J = 6.8 Hz, 2H),
1.88-1.82 (m, 4H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 151.9, 139.4, 138.5,
137.1, 134.7, 132.3, 130.0, 129.6, 129.0, 128.6, 128.3, 128.2, 128.1, 127.9, 122.8,
53.1, 46.6, 46.1, 25.7, 24.9 ppm; HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for
C26H26ClN2O4S, 497.1296; found, 497.1302.
(E)-2-benzyl
1-(1-((N-benzyl-4-methylphenyl)sulfonamido)-2-phenylvinyl)
(S)-pyrrolidine-1,2-dicarboxylate (5r). Foam solid (183 mg, 60%); purified by
column chromatography on silica gel (PE/EtOAc = 3/1); IR (film): νmax 3063, 3031,
2955, 2882, 1729, 1401, 1355, 1164, 694 cm-1; 1H NMR (400 MHz, CDCl3, rotamers)
δ 7.76 (d, J = 8.4 Hz, 1H), 7.69 (d, J = 8.4 Hz, 1H), 7.35-7.31 (m, 4H), 7.29-7.24 (m,
3H), 7.24-7.18 (m, 3H), 7.15-7.10 (m, 5H), 7.10-7.07 (m, 2H), 6.35 (s, 0.56H), 6.21
(s, 0.44H), 5.23-5.12 (m, 2H), 4.50-4.39 (m, 2H), 4.38-4.34 (m, 0.56H), 3.99-3.94 (m,
0.44H), 3.66-3.60 (m, 0.44H), 3.50-3.42 (m, 0.44H), 3.19-3.13 (m, 0.56H), 3.08-3.00
(m, 0.56H), 2.40 (s, 1.69H), 2.38 (s, 1.31H), 2.22-2.12 (m, 1H), 2.08-1.96 (m, 1H),
1.92-1.80 (m, 2H) ppm; 13C{1H} NMR (100 MHz, CDCl3, rotamers) δ 171.9 (172.1),
152.2 (152.0), 143.76 (143.81), 137.2 (137.0), 137.1, 135.7 (135.5), 134.9 (135.0),
132.32 (132.28), 129.93 (129.89), 129.5, 128.8, 128.7, 127.68 (128.63), 128.38
(128.45), 128.25, 128.22, 128.20, 128.04 (128.02), 127.93 (127.97), 127.84 (127.78),
122.9, 67.1 (67.3), 59.5 (59.1), 52.5(52.2), 46.6 (47.2), 29.9 (30.9), 24.3 (23.3), 21.6
ppm; HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for C35H35N2O6S, 611.2210; found,
611.2211.
(E)-1-((N-benzyl-4-methylphenyl)sulfonamido)-2-phenylvinyl
(3S)-3-((tetrahydro-2H-pyran-2-yl)oxy)pyrrolidine-1-carboxylate (5s). Colorless oil
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(176 mg, 61%); purified by column chromatography on silica gel (PE/EtOAc = 4/1);
1H NMR (400 MHz, CDCl3) δ 7.80-7.75 (m, 2H), 7.29-7.19 (m, 6H), 7.15-7.10 (m,
6H), 6.35 (s, 1H), 4.71-4.59 (m, 1H), 4.52-4.44 (m, 2H), 4.42-4.30 (m, 1H), 3.91-3.81
(m, 1H), 3.58-3.42 (m, 3H), 3.24-3.12 (m, 1H), 3.12-3.04 (m, 1H), 2.41 (s, 3H),
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2.08-1.78 (m, 3H), 1.78-1.68 (m, 1H), 1.62-1.50 (m, 4H) ppm; C{1H} NMR (100
MHz, CDCl3) δ 152.2 (152.0), 143.8, 137.3, 137.1, 134.9, 132.5, 129.9, 129.8, 129.5,
128.7, 128.2, 128.19, 128.06, 128.02, 127.8, 122.7 (122.5), 98.1 (97.9), 97.6 (97.5),
75.0 (74.8), 74.1 (74.0), 63.2 (62.9), 62.8 (62.7), 52.7 (52.9), 52.5 (52.6), 51.7 (51.3),
44.8 (44.0), 44.4, 32.6 (31.9), 31.0 (30.2), 25.5 (21.7), 19.9 (19.7), 19.6 ppm; HRMS
(ESI-Orbitrap) m/z: [M + Na]+ calcd for C32H36N2NaO6S, 599.2186; found, 599.2191.
(E)-1-((N-benzyl-4-methylphenyl)sulfonamido)-2-phenylvinyl
piperidine-1-carboxylate (5t). Colorless oil (208 mg, 85%); purified by column
chromatography on silica gel (PE/EtOAc = 4/1); IR (film): νmax 3062, 3029, 2937,
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2857, 1721, 1426, 1356, 1229, 1164, 1058, 814, 693, 659 cm-1; H NMR (400 MHz,
CDCl3) δ 7.76 (d, J = 8.4 Hz, 2H), 7.31-7.27 (m, 2H), 7.26-7.21 (m, 4H), 7.15-7.09
(m, 6H), 6.29 (s, 1H), 4.45 (s, 2H), 3.42-3.36 (m, 2H), 3.09-3.03 (m, 2H), 2.40 (s,
3H), 1.60-1.50 (m, 4H), 1.39-1.31 (m, 2H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ
152.7, 143.7, 137.6, 137.2, 135.0, 132.4, 129.9, 129.5, 128.6, 128.2, 128.1, 128.0,
127.9, 127.8, 122.7, 52.6, 45.3, 25.9, 25.6, 24.3, 21.6 ppm; HRMS (ESI-Orbitrap)
m/z: [M + H]+ calcd for C28H31N2O4S, 491.1999; found, 491.1997.
(E)-1-((N-benzyl-4-methylphenyl)sulfonamido)-2-phenylvinyl
morpholine-4-carboxylate (5u). Foam solid (160 mg, 65%); purified by column
chromatography on silica gel (PE/EtOAc = 3/1); IR (film): νmax 3062, 3030, 2964,
2922, 2859, 1725, 1423, 1356, 1234, 1164, 1115, 1065, 849, 816, 693, 659 cm-1; H
1
NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.0 Hz, 2H), 7.29-7.24 (m, 2H), 7.24-7.21 (m,
2H), 7.20-7.11 (m, 8H), 6.32 (s, 1H), 4.48 (s, 2H), 3.69-3.61 (m, 2H), 3.51-3.46 (m,
2H), 3.46-3.41 (m, 2H), 3.11-3.05 (m, 2H), 2.41 (s, 3H) ppm; 13C{1H} NMR (100
MHz, CDCl3) δ 152.7, 143.9, 137.4, 137.2, 135.1, 132.1, 129.8, 129.5, 128.6, 128.2,
128.1, 127.9, 122.8, 66.6, 66.4, 52.9, 44.6, 44.2, 21.6 ppm; HRMS (ESI-Orbitrap)
m/z: [M + H]+ calcd for C27H29N2O5S, 493.1792; found, 493.1793.
(E)-1-((N-benzyl-4-methylphenyl)sulfonamido)-2-phenylvinyl
azepane-1-carboxylate (5v). Colorless oil (191, 76%), purified by column
chromatography on silica gel (PE/EtOAc = 4/1); IR (film): νmax 3062, 3029, 2927,
2855, 1720, 1356, 1164, 1059, 731 cm-1; H NMR (400 MHz, CDCl3) δ 7.76 (d, J =
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8.4 Hz, 2H), 7.33-7.29 (m, 2H), 7.25-7.19 (m, 4H), 7.16-7.08 (m, 6H), 6.29 (s, 1H),
4.46 (s, 2H), 3.40 (t, J = 6.0 Hz, 2H), 3.09-3.04 (m, 2H), 2.40 (s, 3H), 1.73-1.67 (m,
2H), 1.57-1.51 (m, 2H), 1.51-1.45 (m, 4H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ
153.7, 143.8, 137.5, 137.2, 135.1, 132.5, 129.9, 129.5, 128.6, 128.2, 128.1, 128.0,
127.7, 122.6, 52.5, 47.4, 46.9, 28.6, 28.1, 27.3, 27.1, 21.6 ppm; HRMS (ESI-Orbitrap)
m/z: [M + H]+ calcd for C29H33N2O4S, 505.2156; found, 505.2165.
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2-benzyl
1-((E)-1-((N-benzyl-4-methylphenyl)sulfonamido)-2-phenylvinyl)
(2S,3aS,7aS)-octahydro-1H-indole-1,2-dicarboxylate (5w). Foam solid (255 mg,
77%); purified by column chromatography on silica gel (PE/EtOAc = 3/1); IR (film):
νmax 3063, 3031, 2928, 2857, 1724, 1452, 1357, 1165, 1078, 694 cm-1; 1H NMR (400
MHz, CDCl3, rotamers) δ 7.76 (d, J = 8.0 Hz, 1.24H), 7.68 (d, J = 8.0 Hz, 0.76H),
7.36-7.28 (m, 6H), 7.28-7.24 (m, 2H), 7.21-7.14 (m, 4H), 7.14-7.10 (m, 3H),
7.08-7.02 (m, 2H), 6.31 (s, 0.62H), 6.17 (s, 0.38H), 5.26-5.14 (m, 2H), 4.50-4.39 (m,
2H), 4.36 (t, J = 9.2 Hz, 0.62H), 4.00 (t, J = 9.2 Hz, 0.38H), 3.92-3.84 (m, 0.38H),
3.45-3.37 (m, 0.62H), 2.41 (s, 1.86H), 2.38 (s, 1.14H), 2.32-2.21 (m, 1H), 2.20-2.11
(m, 1H), 2.08-1.91 (m, 1H), 1.76-1.64 (m, 2H), 1.62-1.52 (m, 2H), 1.52-1.45 (m, 1H),
1.45-1.10 (m, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3, rotamers) δ 172.4 (172.6),
152.2 (151.8), 143.7, 137.2, 137.0, 135.8 (135.5), 135.1, 132.4 (132.3), 129.9, 129.6
(129.5), 128.8 (128.5), 128.7, 128.3, 128.27, 128.24, 128.19, 128.1, 128.0 (127.9),
127.8 (127.7), 122.7 (122.9), 67.0 (67.3), 59.5 (59.0), 57.8 (58.4), 52.4 (52.2), 37.2
(36.5), 31.4 (32.6), 27.8 (27.0), 25.8 (25.7), 24.0 (23.6), 21.7 (21.6), 20.3 (20.5) ppm;
HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for C39H41N2O6S, 665.2680; found,
665.2676.
(E)-1-((N-benzyl-4-methylphenyl)sulfonamido)-2-phenylvinyl
3,4-dihydroisoquinoline-2(1H)-carboxylate (5x). Foam solid (189 mg, 70%); purified
by column chromatography on silica gel (PE/EtOAc = 4/1); IR (film): νmax 3062,
3028, 2926, 1724, 1356, 1164, 1108, 692 cm-1; 1H NMR (400 MHz, CDCl3, rotamers)
δ 7.78-7.70 (m, 2H), 7.31-7.25 (m, 3H), 7.24-7.18 (m, 4H), 7.18-7.08 (m, 9H), 6.36
(s, 0.51H), 6.33 (s, 0.49H), 4.58 (s, 0.98H), 4.50 (s, 1.02H), 4.49 (s, 0.98H), 4.20 (s,
1.02H), 3.65 (t, J = 5.6 Hz, 1.02H), 3.31 (t, J = 6.0 Hz, 0.98H), 2.82 (t, J = 5.6 Hz,
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1.02H), 2.65 (t, J = 6.0 Hz, 0.98H), 2.33 (s, 1.47H), 2.27 (s, 1.53H) ppm; C{1H}
NMR (100 MHz, CDCl3, rotamers) δ 152.9, 143.8, 137.7 (137.4), 137.3 (137.2),
135.0, 134.5 (134.2), 132.6 (133.1), 132.3, 129.9, 129.5, 129.0 (128.6), 128.7, 128.2,
128.17, 128.10, 128.04, 128.00, 127.9, 126.9, 126.6 (126.7), 126.2 (126.5), 122.6
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(123.0), 53.1 (52.8), 45.8 (46.0), 41.8 (42.0), 28.8 (29.0), 21.5 ppm; HRMS
(ESI-Orbitrap) m/z: [M + H]+ calcd for C32H31N2O4S, 539.1999; found, 539.2005.
(E)-1-((N-benzyl-4-methylphenyl)sulfonamido)-2-phenylvinyl diethylcarbamate
(5y). White solid (196 mg, 82%); purified by column chromatography on silica gel
(PE/EtOAc = 5/1); mp 79-81 oC; IR (film): νmax 3062, 3029, 2975, 2933, 1722, 1420,
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1164, 1116, 693 cm-1; H NMR (400 MHz, CDCl3, rotamers) δ 7.75 (d, J = 7.2 Hz,
2H), 7.32-7.28 (m, 2H), 7.25-7.20 (m, 4H), 7.17-7.10 (m, 6H), 6.28 (s, 1H), 4.46 (s,
2H), 3.28 (q, J = 7.2 Hz, 2H), 2.98 (q, J = 7.2 Hz, 2H), 2.40 (s, 3H), 1.13 (t, J = 7.2
Hz, 3H), 0.94 (t, J = 7.2 Hz, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3, rotamers) δ
153.3, 143.8, 137.5, 137.2, 135.1, 132.5, 129.9, 129.5, 128.6, 128.2, 128.1, 128.0,
127.8, 122.5, 52.6, 42.3, 41.6, 21.6, 14.2, 13.4 ppm; HRMS (ESI-Orbitrap) m/z: [M +
H]+ calcd for C27H31N2O4S, 479.1999; found, 479.2004.
(E)-1-((N-benzyl-4-methylphenyl)sulfonamido)-2-phenylvinyl
dipropylcarbamate (5z). Colorless oil (205 mg, 81%); purified by column
chromatography on silica gel (PE/EtOAc = 5/1); IR (film): νmax 3062, 3029, 2964,
2932, 2874, 1722, 1418, 1357, 1164, 1118, 693, 658 cm-1; H NMR (400 MHz,
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CDCl3) δ 7.74 (d, J = 8.4 Hz, 2H), 7.32-7.28 (m, 2H), 7.23 (d, J = 8.4 Hz, 2H),
7.20-7.10 (m, 8H), 6.25 (s, 1H), 4.46 (s, 2H), 3.19 (t, J = 7.6 Hz, 2H), 2.94 (t, J = 7.6
Hz, 2H), 2.40 (s, 3H), 1.60-1.51 (m, 2H), 1.46-1.38 (m, 2H), 0.89 (t, J = 7.6 Hz, 3H),
0.82 (t, J = 7.6 Hz, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 153.8, 143.8,
137.7, 137.2, 135.2, 132.5, 129.9, 129.5, 128.6, 128.2, 128.1, 128.0, 127.7, 122.1,
52.5. 49.6, 48.9, 21.8, 21.6, 21.2, 11.3 ppm; HRMS (ESI-Orbitrap) m/z: [M + H]+
calcd for C29H35N2O4S, 507.2312; found, 507.2319.
(E)-1-((N-benzyl-4-methylphenyl)sulfonamido)-2-phenylvinyl
benzyl(methyl)carbamate (5b’). Foam solid (195 mg, 74%); purified by column
chromatography on silica gel (PE/EtOAc = 5/1); IR (film): νmax 3062, 3029, 2924,
1724, 1356, 1164, 1107, 694 cm-1; 1H NMR (400 MHz, CDCl3, rotamers) δ 7.74 (d, J
= 8.0 Hz, 1H), 7.68 (d, J = 7.2 Hz, 1H), 7.36-7.31 (m, 3H), 7.30-7.21 (m, 5H),
7.18-7.08 (m, 8H), 7.08-7.03 (m, 1H), 6.37 (s, 0.53H), 6.34 (s, 0.47H), 4.48 (s, 1H),
4.44 (s, 2H), 4.11 (s, 1H), 2.84 (s, 1.41H), 2.58 (s, 1.59H), 2.34 (s, 1.59H), 2.26 (s,
1.41H) ppm; 13C{1H} NMR (100 MHz, CDCl3, rotamers) δ 154.3 (153.9), 143.8
(143.9), 138.0, 137.2 (137.4), 136.9 (137.0), 135.7, 135.0, 132.4 (132.3), 129.9
(129.8), 129.5 (129.6), 128.8, 128.7, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.3,
122.3 (123.0), 53.01 (53.04), 52.6 (52.4), 33.8 (34.6), 21.6 ppm; HRMS
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(ESI-Orbitrap) m/z: [M + H]+ calcd for C31H31N2O4S, 527.1999; found, 527.1995.
(E)-1-((N-benzyl-4-methylphenyl)sulfonamido)-2-phenylvinyl
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8
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dibenzylcarbamate (5c’). White solid (127 mg, 42%); purified by column
chromatography on silica gel (PE/EtOAc = 5/1); mp 115-117 oC; IR (film): νmax 3062,
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3029, 2925, 1722, 1452, 1417, 1357, 1213, 1164, 1085, 697 cm-1; H NMR (400
MHz, CDCl3) δ 7.68 (d, J = 8.4 Hz, 2H), 7.38-7.32 (m, 6H), 7.32-7.27 (m, 2H),
7.27-7.25 (m, 2H), 7.25-7.22 (m, 2H), 7.19-7.16 (m, 3H), 7.15-7.08 (m, 3H),
7.08-7.04 (m, 2H), 6.97 (d, J = 8.0 Hz, 2H), 6.42 (s, 1H), 4.45 (s, 2H), 4.40 (s, 2H),
4.01 (s, 2H), 2.22 (s, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 154.3, 143.8,
137.7, 137.0, 136.8, 136.6, 134.9, 132.3, 129.9, 129.6, 128.8, 128.7, 128.5, 128.3,
128.2, 128.1, 128.0, 127.9, 127.8, 127.6, 122.7, 52.7, 49.7, 49.1, 21.5 ppm; HRMS
(ESI-Orbitrap) m/z: [M + Na]+ calcd for C37H34N2NaO4S, 625.2132; found, 625.2137.
(E)-allyl (1-((N-benzyl-4-methylphenyl)sulfonamido)-2-phenylvinyl) carbonate
(7a). Foam solid (190 mg, 82%); purified by column chromatography on silica gel
(PE/EtOAc = 8/1); 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.4 Hz, 2H), 7.28-7.24
(m, 4H), 7.22-7.18 (m, 3H), 7.14-7.04 (m, 5H), 6.40 (s, 1H), 6.97-5.86 (m, 1H),
5.40-5.28 (m, 2H), 4.63-4.60 (m, 2H), 4.37 (s, 2H), 2.42 (s, 3H) ppm; 13C{1H} NMR
(100 MHz, CDCl3) δ 152.8, 144.1, 138.1, 136.5, 134.3, 131.9, 131.2, 129.6, 129.5,
128.7, 128.4, 128.3, 128.2, 128.1, 121.6, 119.4, 69.2, 52.5, 21.7 ppm; HRMS
(ESI-Orbitrap) m/z: [M + Na]+ calcd for C26H25NNaO5S, 486.1346; found, 486.1350.
(E)-allyl (1-((N,4-dimethylphenyl)sulfonamido)-2-phenylvinyl) carbonate (7b).
White solid (112 mg, 58%); purified by column chromatography on silica gel
(PE/EtOAc = 8/1); mp 76-78 oC; IR (film): νmax 3061, 3027, 2947, 1762, 1357, 1243,
1206, 943, 711 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.4 Hz, 2H), 7.50 (d,
J = 8.4 Hz, 2H), 7.38-7.33 (m, 2H), 7.32-7.27 (m, 3H), 6.30 (s, 1H), 5.89-5.78 (m,
1H), 5.35-5.26 (m, 2H), 4.47-4.44 (m, 2H), 3.03 (s, 3H), 2.42 (s, 3H) ppm; C{1H}
13
NMR (100 MHz, CDCl3) δ 153.2, 144.0, 140.6, 136.1, 131.7, 131.0, 129.7, 128.8,
128.7, 128.6, 128.0, 119.4, 118.6, 69.2, 36.8, 21.7 ppm; HRMS (ESI-Orbitrap) m/z:
[M + Na]+ calcd for C20H21NNaO5S, 410.1033; found, 410.1040.
(E)-allyl (1-((N-allyl-4-methylphenyl)sulfonamido)-2-phenylvinyl) carbonate
(7c). Colorless oil (158 mg; 77%); purified by column chromatography on silica gel
(PE/EtOAc = 8/1); IR (film): νmax 3065, 3026, 2984, 2924, 1763, 1356, 1232, 1163,
663 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.4 Hz, 2H), 7.53-7.49 (m, 2H),
7.35-7.26 (m, 5H), 6.47 (s, 1H), 5.95-5.85 (m, 1H), 5.68-5.59 (m, 1H), 5.38-5.28 (m,
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2H), 5.08-4.98 (m, 2H), 4.61-4.58 (m, 2H), 3.93-3.90 (m, 2H), 2.42 (s, 3H) ppm;
13C{1H} NMR (100 MHz, CDCl3) δ 152.7, 144.1, 138.6, 136.6, 132.0, 131.8, 131.2,
129.6, 128.9, 128.6, 128.5, 128.4, 120.9, 119.8, 119.4, 69.2, 52.4, 21.7 ppm; HRMS
(ESI-Orbitrap) m/z: [M + Na]+ calcd for C22H23NNaO5S, 436.1189; found, 436.1191.
(E)-allyl (1-((N-butyl-4-methylphenyl)sulfonamido)-2-phenylvinyl) carbonate
(7d). Colorless oil (75 mg; 35%); purified by column chromatography on silica gel
(PE/EtOAc = 8/1); IR (film): νmax 3062, 2959, 2873, 1764, 1357, 1230, 1166, 968,
758 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.4 Hz, 2H), 7.59-7.55 (m, 2H),
7.34-7.27 (m, 5H), 6.51 (s, 1H), 5.96-5.85 (m, 1H), 5.38-5.28 (m, 2H), 4.63-4.60 (m,
2H), 3.21 (t, J = 7.6 Hz, 2H), 2.42 (s, 3H), 1.48-1.42 (m, 2H), 1.17-1.10 (m, 2H), 0.73
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(t, J = 7.6 Hz, 3H) ppm; C{1H} NMR (100 MHz, CDCl3) δ 152.9, 144.0, 138.2,
136.4, 132.0, 131.2, 129.6, 129.0, 128.6, 128.4, 122.0, 119.4, 69.2, 48.9, 29.9, 21.7,
20.0, 13.6 ppm; HRMS (ESI-Orbitrap) m/z: [M + Na]+ calcd for C23H27NNaO5S,
452.1502; found, 452.1509.
(E)-allyl (1-(N-benzylmethylsulfonamido)-2-phenylvinyl) carbonate (7e).
Collorless oil (153 mg, 79%); purified by column chromatography on silica gel
(PE/EtOAc = 8/1); IR (film): νmax 3063, 3029, 2935, 1763, 1352, 1232, 1157, 955,
1
758 cm-1; H NMR (400 MHz, CDCl3) δ 7.38-7.34 (m, 2H), 7.34-7.30 (m, 2H),
7.30-7.26 (m, 2H), 7.25-7.22 (m, 4H), 6.46 (s, 1H), 6.03-5.92 (m, 1H), 5.45-5.32 (m,
13
2H), 4.74-4.70 (m, 2H), 4.49 (s, 2H), 2.86 (s, 3H) ppm; C{1H} NMR (100 MHz,
CDCl3) δ 152.8, 139.2, 134.6, 131.8, 131.0, 129.7, 128.7, 128.6, 128.55, 128.50,
128.4, 120.1, 120.1, 69.5, 53.4, 41.7 ppm; HRMS (ESI-Orbitrap) m/z: [M + Na]+
calcd for C20H21NNaO5S, 410.1033; found, 410.1038.
(E)-1-((N-benzyl-4-methylphenyl)sulfonamido)-2-phenylvinyl
but-3-en-2-yl
carbonate (7f). White solid (129 mg; 54%); purified by column chromatography on
o
silica gel (PE/EtOAc = 8/1); mp 97-98 C; IR (film): νmax 3063, 3030, 2984, 2932,
1
1762, 1357, 1240, 1165, 1034, 694 cm-1; H NMR (400 MHz, CDCl3) δ 7.76 (d, J =
7.2 Hz, 2H), 7.29-7.22 (m, 4H), 7.22-7.18 (m, 3H), 7.13-7.08 (m, 1H), 7.08-7.04 (m,
4H), 6.38 (s, 1H), 5.89-5.79 (m, 1H), 5.32-5.19 (m, 2H), 5.19-5.12 (m, 1H), 4.37 (s,
2H), 2.42 (s, 3H), 1.37 (d, J = 6.4 Hz, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ
152.3, 144.0, 138.2, 136.7, 136.6, 134.4, 132.0, 129.6, 128.7, 128.4, 128.3, 128.2,
128.1, 128.0, 121.5, 117.0, 76.3, 52.6, 21.7, 20.0 ppm; HRMS (ESI-Orbitrap) m/z: [M
+ Na]+ calcd for C27H27NNaO5S, 500.1502; found, 500.1507.
(E)-1-((N-benzyl-4-methylphenyl)sulfonamido)-2-phenylvinyl
cinnamyl
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carbonate (7g). White solid (191 mg, 71%); purified by column chromatography on
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6
o
silica gel (PE/EtOAc = 8/1); mp 107-108 C; IR (film): νmax 3062, 3029, 2950, 1763,
1356, 1231, 1164, 693 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.0 Hz, 2H),
7.42-7.38 (m, 2H), 7.38-7.33 (m, 2H), 7.32-7.26 (m, 3H), 7.24-7.19 (m, 5H),
7.14-7.09 (m, 1H), 7.09-7.05 (m, 4H), 6.70 (d, J = 16.0 Hz, 1H), 6.41 (s, 1H),
6.31-6.22 (m, 1H), 4.78 (dd, J = 6.4, 1.2 Hz, 2H), 4.38 (s, 2H), 2.35 (s, 3H) ppm;
13C{1H} NMR (100 MHz, CDCl3) δ 152.9, 144.1, 138.2, 136.5, 136.0, 135.5, 134.3,
131.9, 129.7, 129.6, 128.8, 128.7, 128.6, 128.3, 128.2, 128.1, 126.9, 122.0, 121.7,
69.2, 52.6, 21.6 ppm; HRMS (ESI-Orbitrap) m/z: [M + Na]+ calcd for C32H29NNaO5S,
562.1659; found, 562.1658.
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(E)-1-((N-benzyl-4-methylphenyl)sulfonamido)-2-phenylvinyl
prop-2-yn-1-yl
carbonate (7h). Colorless oil (141 mg, 61%); purified by column chromatography on
silica gel (PE/EtOAc = 8/1); IR (film): νmax 3063, 3031, 2919, 1769, 1356, 1229,
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1164, 984, 694 cm-1; H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.0 Hz, 2H),
7.29-7.25 (m, 4H), 7.23-7.19 (m, 3H), 7.14-7.03 (m, 5H), 6.42 (s, 1H), 4.71 (d, J =
2.8 Hz, 2H), 4.37 (m, 2H), 2.57 (t, J = 2.4 Hz, 1H), 2.43 (s, 3H) ppm; 13C{1H} NMR
(100 MHz, CDCl3) δ 152.4, 144.2, 138.1, 136.3, 134.2, 131.7, 129.7, 129.6, 128.8,
128.3, 128.2, 128.1, 121.8, 76.6, 76.3, 56.0, 52.5, 21.7 ppm; HRMS (ESI-Orbitrap)
m/z: [M + Na]+ calcd for C26H23NNaO5S, 484.1189; found, 484.1194.
(E)-1-((N-benzyl-4-methylphenyl)sulfonamido)-2-(4-bromophenyl)vinyl
(tetrahydro-2H-pyran-2-yl)carbamate (9). White solid (111 mg, 38%); purified by
o
column chromatography on silica gel (PE/EtOAc = 2/1); mp 127-129 C; IR (film):
νmax 3064, 3033, 2943, 2853, 1750, 1526, 1353, 1163, 1033, 717 cm-1; 1H NMR (400
MHz, CDCl3) δ 7.73 (d, J = 8.0 Hz, 2H), 7.25-7.16 (m, 6H), 7.16-7.09 (m, 3H), 6.97
(d, J = 8.4 Hz, 2H), 6.29 (s, 1H), 5.24-5.16 (m, 1H), 4.87-4.79 (m, 1H), 4.40 (s, 2H),
4.01-3.94 (m, 1H), 3.63-3.53 (m, 1H), 2.42 (s, 3H), 1.92-1.85 (m, 1H), 1.82-1.74 (m,
13
1H), 1.60-1.54 (m, 1H), 1.54-1.48 (m, 2H), 1.39-1.30 (m, 1H) ppm; C{1H} NMR
(100 MHz, CDCl3) δ 152.7, 144.2, 137.7, 136.7, 134.4, 131.2, 130.1, 130.0, 129.6,
128.3, 128.2, 121.9, 121.6, 80.0, 67.2, 52.5, 31.5, 25.0, 22.8, 21.7 ppm; HRMS
(ESI-Orbitrap) m/z: [M + H]+ calcd for C28H30BrN2O5S, 585.1053; found, 585.1058.
General Procedure for Synthesis of 11 and 14.
General Procedure for Synthesis of 11a-11s, 14a-14f.
To a solution of 10 or 13 (1.0 mmol) in dry THF (10 mL) was dropwise added newly
prepared Grignard reagent (2.0 mmol) at -78oC. The reaction mixture was stirred for
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1.5 h and quenched with aqueous NH4Cl (10 mL). Extracted with ethyl acetate (20
mL × 3), and the combined organic layers were washed with brine. Dried, filtered,
and concentrated, crude product was got. Cu(OTf)2 (18 mg, 0.05 mmol) was added to
a solution of the above crude product and ynamide (0.5 mmol) in DCM (2 mL) and
the mixture was stirred for 1 h at 0 oC to room temperature. The reaction mixture was
quenched with aqueous NaHCO3. Extracted with DCM (10 ml × 3), and the combined
organic layers were washed with brine. Dried, filtered, and concentrated, the residue
was purified by flash chromatography on silica gel.
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(E)-1-((N,4-Dimethylphenyl)sulfonamido)-2-phenylvinyl-(S)-(3-((tert-butyldime
thylsilyl)oxy)-4-oxo-4-phenylbutyl)carbamate (11a). This compound was obtained in
85% purity as judged by NMR analysis. Colorless Oil (262 mg, 84%); purified by
12
column chromatography on silica gel (PE/EtOAc = 5/1); [α]D = -3.29 (c 0.850,
CHCl3); IR (film): νmax 3440, 3061, 3027, 2951, 2927, 2855, 1746, 1672, 837, 777
1
cm-1; H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 7.6 Hz, 2H), 7.75 (d, J = 8.0 Hz,
2H), 7.63-7.57 (m, 1H), 7.51-7.45 (m, 4H), 7.36-7.30 (m, 2H), 7.29-7.25 (m, 3H),
6.13 (s, 1H), 5.11 (s, 1H), 5.02-4.95 (m, 1H), 3.24-3.14 (m, 2H), 3.02 (s, 3H), 2.36 (s,
13
3H), 1.99-1.90 (m, 2H), 0.92 (s, 9H), 0.05 (s, 3H), 0.02 (s, 3H) ppm; C{1H} NMR
(100 MHz, CDCl3) δ 200.7, 153.9, 143.9, 140.2, 136.4, 134.7, 133.6, 132.2, 129.6,
129.0, 128.8, 128.7, 128.6, 128.2, 127.9, 118.5, 75.4, 38.1, 36.6, 35.0, 25.9, 21.6,
18.4, -4.5, -5.1 ppm; HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for C33H43N2O6SSi,
623.2606; found, 623.2601.
(E)-1-((N,4-Dimethylphenyl)sulfonamido)-2-phenylvinyl-(S)-(3-((tert-butyldime
thylsilyl)oxy)-4-(4-fluorophenyl)-4-oxobutyl)carbamate (11b). Colorless Oil (218 mg,
13
68%); purified by column chromatography on silica gel (PE/EtOAc = 5/1); [α]D
=
-7.55 (c 0.94, CHCl3); IR (film): νmax 3440, 3065, 3027, 2952, 2928, 2856, 1747,
1
1673, 1597, 1355, 778 cm-1; H NMR (400 MHz, CDCl3) δ 8.12-8.06 (m, 2H), 7.75
(d, J = 8.0 Hz, 2H), 7.44 (d, J = 7.6 Hz, 2H), 7.35-7.27 (m, 5H), 7.18-7.12 (m, 2H),
6.14 (s, 1H), 5.07 (s, 1H), 4.88-4.82 (m, 1H), 3.25-3.16 (m, 2H), 3.02 (s, 3H), 2.37 (s,
3H), 1.98-1.91 (m, 2H), 0.90 (s, 9H), 0..05 (s, 3H), -0.01 (s, 3H) ppm; 13C{1H} NMR
(100 MHz, CDCl3) δ 199.2, 167.3, 164.7, 153.9, 144.0, 140.2, 136.4, 132.2, 132.1,
132.0, 129.6, 128.7, 128.6, 128.2, 127.9, 118.4, 116.1, 115.8, 75.9, 38.1, 36.6, 35.2,
25.9, 21.6, 18.3, -4.6, -5.1 ppm; HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for
C33H42FN2O6SSi, 641.2511; found, 641.2515.
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(E)-1-((N,4-Dimethylphenyl)sulfonamido)-2-phenylvinyl-(S)-(3-((tert-butyldime
thylsilyl)oxy)-4-oxo-4-(p-tolyl)butyl)carbamate (11c). Colorless Oil (248 mg, 78%);
purified by column chromatography on silica gel (PE/EtOAc = 5/1); [α]D12 = -1.28 (c
1.48, CHCl3); IR (film): νmax 3424, 3066, 3028, 2952, 2928, 2856, 1747, 1671, 1355,
836, 779 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 7.6 Hz, 2H), 7.75 (d, J = 7.2
Hz, 2H), 7.47 (d, J = 7.6 Hz, 2H), 7.36-7.31 (m, 2H), 7.29-7.24 (m, 5H), 6.12 (s, 1H),
5.14 (s, 1H), 4.98-4.93 (m, 1H), 3.22-3.13 (m, 2H), 3.02 (s, 3H), 2.42 (s, 3H), 2.36 (s,
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3H), 1.97-1.88 (m, 2H), 0.92 (s, 9H), 0.04 (s, 3H), 0.02 (s, 3H) ppm; C{1H} NMR
(100 MHz, CDCl3) δ 200.2, 153.9, 144.6, 143.9, 140.2, 136.5, 132.2, 132.1, 129.6,
129.5, 129.2, 128.7, 128.6, 128.2, 127.9, 118.4, 75.4, 38.2, 36.6, 35.1, 25.9, 21.8,
21.6, 18.4, -4.5, -5.1 ppm; HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for
C34H45N2O6SSi, 637.2762; found, 637.2766.
(E)-1-((N,4-Dimethylphenyl)sulfonamido)-2-phenylvinyl-(S)-(3-((tert-butyldime
thylsilyl)oxy)-4-(4-methoxyphenyl)-4-oxobutyl)carbamate (11d). Colorless Oil (248
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mg, 76%); purified by column chromatography on silica gel (PE/EtOAc = 2/1); [α]D
= -1.48 (c 1.88, CHCl3); IR (film): νmax 3421, 3033, 3028, 2953, 2929, 1746, 1659,
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1599, 1354, 1257, 837, 779 cm-1; H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 8.8 Hz,
2H), 7.75 (d, J = 8.4 Hz, 2H), 7.46 (d, J = 7.2 Hz, 2H), 7.35-7.30 (m, 2H), 7.28-7.24
(m, 3H), 6.94 (d, J = 9.2 Hz, 2H), 6.11 (s, 1H), 5.15 (s, 1H), 4.91-4.86 (m, 1H), 3.87
(s, 3H), 3.25-3.13 (m, 2H), 3.01 (s, 3H), 2.36 (s, 3H), 1.97-1.90 (m, 2H), 0.91 (s, 9H),
0.04 (s, 3H), 0.01 (s, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 199.1, 166.9,
153.9, 143.9, 140.2, 136.4, 132.2, 131.5, 129.6, 128.7, 128.6, 128.2, 127.9, 127.4,
118.4, 114.0, 75.6, 55.6, 38.2, 36.6, 35.3, 25.9, 21.6, 18.4, -4.5, -5.1 ppm; HRMS
(ESI-Orbitrap) m/z: [M + H]+ calcd for C34H45N2O7SSi, 653.2711; found, 653.2716.
(E)-1-((N,4-Dimethylphenyl)sulfonamido)-2-phenylvinyl-(S)-(4-(4-(tert-butyl)p
henyl)-3-((tert-butyldimethylsilyl)oxy)-4-oxobutyl)carbamate (11e). Colorless Oil
(156 mg, 46%); purified by column chromatography on silica gel (PE/EtOAc = 5/1);
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[α]D = +1.29 (c 0.805, CHCl3); IR (film): νmax 3442, 3061, 2955, 2928, 1748, 1692,
1603, 1358, 1049, 838, 779 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.0 Hz,
2H), 7.75 (d, J = 8.4 Hz, 2H), 7.51-7.45 (m, 4H), 7.36-7.30 (m, 2H), 7.29-7.24 (m,
3H), 6.16 (s, 1H), 5.13 (s, 1H), 5.04-4.98 (m, 1H), 3.26-3.14 (m, 2H), 3.02 (s, 3H),
2.36 (s, 3H), 1.98-1.84 (m, 2H), 1.34 (s, 9H), 0.93 (s, 9H), 0.05 (s, 6H) ppm; 13C{1H}
NMR (100 MHz, CDCl3) δ 200.1, 157.5, 153.9, 143.9, 140.3, 136.5, 132.3, 132.1,
129.6, 128.9, 128.7, 128.6, 128.2, 127.9, 125.8, 118.5, 75.2, 38.2, 36.6, 35.3, 35.0,
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The Journal of Organic Chemistry
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31.2, 25.9, 21.6, 18.4, -4.4, -5.1 ppm; HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for
C37H51N2O6SSi, 679.3232; found, 679.3237.
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(E)-1-((N,4-Dimethylphenyl)sulfonamido)-2-phenylvinyl-(S)-(4-([1,1'-biphenyl]
-4-yl)-3-((tert-butyldimethylsilyl)oxy)-4-oxobutyl)carbamate (11f). Colorless Oil
(266 mg, 76%); purified by column chromatography on silica gel (PE/EtOAc = 5/1);
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[α]D = -1.47 (c 1.29, CHCl3); IR (film): νmax 3440, 2953, 2928, 1745, 1669, 1354,
836, 695 cm-1; H NMR (400 MHz, CDCl3) δ 8.13-8.07 (m, 2H), 7.80-7.74 (m, 2H),
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7.73-7.68 (m, 2H), 7.67-7.61 (m, 2H), 7.54-7.40 (m, 6H), 7.33-7.27 (m, 4H), 6.12 (s,
1H), 5.12 (s, 1H), 5.03-4.97 (m, 1H), 3.30-3.16 (m, 2H), 3.02 (s, 3H), 2.37 (s, 3H),
2.04-1.94 (m, 2H), 0.93 (s, 9H), 0.11-0.04 (m, 6H) ppm; C{1H} NMR (100 MHz,
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CDCl3) δ 200.2, 153.9, 146.3, 143.9, 140.2, 139.8, 136.4, 133.2, 132.2, 129.7, 129.6,
129.2, 128.7, 128.6, 128.2, 127.9, 127.4, 118.5, 75.5, 38.1, 36.6, 35.1, 25.9, 21.6,
18.4, -4.5, -5.1 ppm; HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for C39H47N2O6SSi,
699.2919; found, 699.2918.
(E)-1-((N,4-Dimethylphenyl)sulfonamido)-2-phenylvinyl-(S)-(3-((tert-butyldime
thylsilyl)oxy)-4-(3-methoxyphenyl)-4-oxobutyl)carbamate (11g). Colorless Oil (235
mg, 72%); purified by column chromatography on silica gel (PE/EtOAc = 3/1); This
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compound was obtained in 92% purity as judged by NMR analysis. [α]D = -1.41 (c
0.620, CHCl3); IR (film): νmax 3440, 3065, 3027, 2951, 2928, 1746, 1695, 1355, 1258,
1047, 838, 779 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.4 Hz, 2H), 7.57 (d,
J = 7.6 Hz, 1H), 7.53-7.50 (m, 1H), 7.48-7.44 (m, 2H), 7.40-7.39 (m, 4H), 7.28-7.26
(m, 1H), 7.26-7.23 (m, 1H), 7.16-7.11 (m, 1H), 6.13 (s, 1H), 5.13 (s, 1H), 5.00-4.95
(m, 1H), 3.86 (s, 3H), 3.24-3.14 (m, 2H), 3.01 (s, 3H), 2.36 (s, 3H), 2.00-1.87 (m,
2H), 0.92 (s, 9H), 0.05 (s, 3H), 0.04 (s, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ
200.4, 160.0, 153.9, 143.9, 140.2, 136.5, 136.0, 132.2, 129.8, 129.6, 128.7, 128.6,
128.2, 127.9, 121.4, 120.0, 118.4, 113.4, 75.3, 55.6, 38.1, 36.6, 35.0, 25.9, 21.6, 18.4,
-4.5, -5.1 ppm; HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for C34H45N2O7SSi,
653.2711; found, 653.2714.
(E)-1-((N,4-Dimethylphenyl)sulfonamido)-2-phenylvinyl-(S)-(3-((tert-butyldime
thylsilyl)oxy)-4-(2-methoxyphenyl)-4-oxobutyl)carbamate (11h). Foam solid (137
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mg, 42%); purified by column chromatography on silica gel (PE/EtOAc = 2/1); [α]D
= -8.50 (c 1.00, CHCl3); IR (film): νmax 3439, 3065, 3026, 2950, 2928, 1746, 1676,
1355, 1246, 837, 712 cm-1; H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.4 Hz, 2H),
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7.66-7.62 (m, 1H), 7.50-7.46 (m, 3H), 7.35-7.30 (m, 2H), 7.28-7.23 (m, 3H),
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