Thermal Rearrangement of Sulfamoyl Azides: Reactivity and Mechanistic Study

Article abstract of DOI:10.1021/acs.joc.7b00308

The rearrangement of sulfamoyl azides under thermal conditions to form a C-C bond while breaking two C-N bonds is reported. Mechanistic study shows that this reaction goes through a Curtius-type rearrangement to form a 1,1-diazene, then which rearranges possibly through both a concerted rearrangement process and a stepwise radical process. This rearrangement could be used in the synthesis of complex biologically active molecules, such as sterols, and piperine derivatives.

Full text of DOI:10.1021/acs.joc.7b00308

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Article
Thermal Rearrangement of Sulfamoyl
Azides: Reactivity and Mechanistic Study
Xiaodong Zou, Jiaqi Zou, Lizheng Yang, Guigen Li, and Hongjian Lu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b00308 • Publication Date (Web): 17 Apr 2017
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Thermal Rearrangement of Sulfamoyl Azides: Reactivity
and Mechanistic Study
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Xiaodong Zou, Jiaqi Zou, Lizheng Yang, Guigen Li and Hongjian Lu*
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Institute of Chemistry and BioMedical Sciences, Jiangsu Key Laboratory of
Advanced Organic Materials, School of Chemistry and Chemical Engineering,
Nanjing University, Nanjing, 210093, China
-N2
path a
a
R1
R2
N
concerted
-N2
R1
R2
- SO2
N
R1
R2
N
N
N
O2S
N
b
R1
+
R2
Major
Product
Curtius-type
rearrangement
-N2
path b
1,1-diazene
stepwise
ABSTRACT: The rearrangement of sulfamoyl azides under thermal conditions to
form a C–C bond while breaking two C–N bonds is reported. Mechanistic study
shows that this reaction goes through a Curtiusꢀtype rearrangement to form a
1,1ꢀdiazene, then which rearranges possibly through both a concerted rearrangement
process and a stepwise radical process. This rearrangement could be used in the
synthesis of complex biologically active molecules such as sterols, and piperine
derivatives.
Introduction
The Curtius rearrangement of an acyl azide into an isocyanate via an acyl nitrene
intermediate is a reliable method for the synthesis of amines and their derivatives.1 It
has been widely used in many aspects of chemical industry from synthetic chemistry,
medicinal chemistry to material sectors.2 There have been however very few reports
of Curtiusꢀtype rearrangements via other αꢀoxo nitrene species, such as phosphoryl
nitrenes3 or sulfonyl nitrenes4. Consequently, development of an efficient
Curtiusꢀtype rearrangement via other species in place of acyl nitrenes to enlarge the
applications of this methodology is of interest.
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The sulfonyl nitrene species is often thought to be involved as transient
intermediates in many organic reactions,5,6 such as aziridination reactions and C–H
amidation reactions, and can even react with different common solvents, such as
cyclohexane5g and benzene5h prior to rearrangement. Due to its high reactivity, the
sulfonyl nitrene species was thus thought to be unlikely to be involved in a
Curtiusꢀtype rearrangement.7 and indeed, little experimental evidence of a
Curtiusꢀtype rearrangement of sulfonyl azides has been reported.8,9 An example is the
formation of the product PhNHSO2OMe in methanol,8 and another one is observed
directly using matrix isolation techniques.5e,9 There appears to be no report of Curtius
rearrangements via sulfonyl nitrenes used synthetically because the intermediate
sulfonyl nitrene species reacts readily with solvents. In this paper, we report the
thermal decomposition of sulfamoyl azides R1R2NSO2N3, in which a Curtiusꢀtype
rearrangement occurs under relatively mild thermal conditions to form a nitrogen
stabilized nitrene, a 1,1ꢀdiazene, which then efficiently rearranges to generate a new
C–C bond simultaneously breaking two C–N bonds.
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Results and Discussion
Sulfamoyl azides are chemically stable even in strong basic or acidic conditions10
and are thermally stable up to at least 100 °C in the absence of solvent.11 They have
recently been characterized as a new class of effective nitrene sources for
metalꢀcatalyzed C–H amination11,12 as well as a new type of azide for applications in
click chemistry.13 In comparison with the widely used alkylsulfonyl and arylsulfonyl
azides, the potential applications of sulfamoyl azides in organic synthesis have not
been fully explored and it is of interest to examine the rearrangement of this
sulfamoyl
nitrene.
Sulfamoyl
azide
(1a),
prepared
from
Nꢀbenzylꢀ1ꢀ(4ꢀmethoxyphenyl)methanamine in one step (see supporting information
(SI)), was used as the starting material (Table 1). The rearrangement of 1a was
performed by heating a solution in methanol (entry 1) and it was found that the
hydrocarbon product (2a) was formed at 80 °C. No evidence was found of products
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formed by reaction with methanol. The decomposition temperature of sulfamoyl
azides in solvent is much lower than that of arylsulfonyl azides.5g Different solvents
were screened (Table 1, entries 1ꢀ9) and dioxane was found to be optimal. No C–H
abstraction or olefin aziridination products were obtained in toluene and dioxane.5
This process may be thermodynamically favored because it generates two equivalents
of N2 and one of SO2. The yield was slightly decreased in the absence of 4Å
molecular sieves (MS) or without the protection of nitrogen (entries 10ꢀ12). When the
reaction was decreased to 60 °C, no rearrangement product (2a) was observed (entry
13). Upon increasing the temperature to 100 °C, the yield of the reaction was slightly
decreased as side reactions were observed (entry 14).
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Table 1. Optimization of Reaction Conditionsa
entry
1
solvent
MeOH
DMF
temp (0C)
80
4Å MS
add
add
add
add
add
add
add
add
add
add
no
yield(%)b
31
2
80
38
3
tBuOH
80
41
4
PhCF3
80
37
5
H2O
80
38
64(62c)
6
DCE
80
7
MeCN
Toluene
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
80
32
8
80
37
9
80
80(80c)
85(85c)
70(71c)
50
10d
11d
12
13d
14d
80
80
80
no
60
add
add
<1
77(76c)
100
a Reaction conditions: sulfamoyl azide 1a (0.2 mmol), 4Å MS (50 mg) and solvent (2
mL), 24 h. b NMR yields. c Isolated yields. d Under nitrogen atmosphere.
With the optimized reaction conditions in hand, various sulfamoyl azides
containing different benzyl groups were screened (Table 2). Symmetric bisBenzyls
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(2b and 2c) and unsymmetric bisBenzyls (2dꢀl) were formed in high yields. Various
functional groups, such as methoxy, nitrile, nitro, fluoride, chloride, bromide, sulfide,
trifluoromethyl groups were tolerated and electronꢀrich and electronꢀwithdrawing
substituents on the phenyl rings failed to affect the reactivity. The sulfamoyl azide
derived from a secondary amine worked well in the reaction (2l) and heterocyclic
rings, such as pyridine, furan, thiophene were all tolerated, affording the
corresponding bisBenzyls containing heterocyclic rings (2mꢀp) in good yields.
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Table 2. Synthesis of BisBenzyls.a,b
O
O
O
2b
2c
2d
74%
92%
81%
F
Br
Cl
O
O
O
2e 83%
2f 89%
2g 95%
CF3
CN
NO2
CF3
O
O
O
2h 83%
2i 85%
2j 79%
N
S
O
O
2k 75%
2l 86%
2m 76%
O
S
O
S
O
NO2
2n 95%c
2p 78%c
2o
89%
a
The optimized conditions: sulfamoyl azide 1 (0.2 mmol), 4Å MS (50 mg) and
dioxane (2 mL), 80 oC , under nitrogen atmosphere, 24 h. b Isolated yields. c 48 h.
In addition to these benzyl groups, acyclic and cyclic alkyl groups were tested
(Table 3). Both electronꢀdeficient and electronꢀrich benzyl groups formed a C–C bond
with the cyclopentyl group in moderate yields (2qꢀs). Substrates containing functional
groups, such as CF3, indoles and esters are tolerated in this reaction (2tꢀv). αꢀAmino
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acid derivatives can be used as substrates, and form new carboxylic acid derivatives
with good yields (2wꢀx). Interestingly, compounds with tertiary carbons can be used
and generate the desired product in acceptable yield (2y).
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When the chiral αꢀamino acid derivative (1x, ee = 56%) was used as the substrate,
the carboxylic acid derivative (2x) was formed with 31% ee (Scheme 1, eq 1). It was
found that the reaction of NꢀbenzylꢀNꢀ(4ꢀmethoxybenzyl)sulfamoyl azide (1a)
afforded the desired product (2a) in 85% yield along with small amounts of the
crossover coupling products 2b and 2c (eq 2). When a mixture of 1b and 1c was used
as the starting material, the selfꢀcoupling products 2b and 2c were still the major
products along with a small amount of the crossover coupling product 2a (eq 3).
These results suggest that this process involves both stepwise and concerted reaction
mechanisms, the latter being the major pathway of the reaction.
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Table 3. Synthesis of Benzyl Derivatives.a,b
aThe optimized conditions: sulfamoyl azide 1 (0.2 mmol), 4Å MS (50 mg) and
dioxane (2 mL), 80 oC , under nitrogen, 24 h. bIsolated yields.
Scheme 1. Mechanistic Studies
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CO2Et
Ph
Ph
COOEt
N2
4Å MS,
N
(1)
dioxane, 80 oC, 24 h
O
O2SN3
O
80% yield
1x (56% ee)
2x (31% ee)
7
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9
N2
4Å MS,
1a
2a
+
2b
+
2c
(2)
(3)
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dioxane, 80 oC, 24 h
85%
6%
6%
4Å MS, N2
dioxane, 80 oC, 24 h
1b
1.0 equiv
+
1c
2a
+
2b
+
2c
78%
13%
85%
1.0 equiv
N
4Å MS,
N2
(4)
dioxane 80 oC 24 h
55% yield
O2SN3
O
O
1z
2z
Experiments using 2,2,6,6ꢀtetramethylpiperidineꢀ1ꢀoxyl (TEMPO) as a radical
trapping reagent (Scheme 2) were conducted and resulted in a decrease in the yield of
product 2b and an increase in formation of the radical trapping product 2b′ when the
amount of TEMPO is increased. When more than one and half equivalents of TEMPO
were used, the ratio of desired products (2b and 2b′) is approximately constant at
1.3/1, which may imply that limited amount of benzyl radical is involved. This result
suggests that the reaction may proceed via two pathways, a free radical process
affording the target products and crossover coupling products, and a rearrangement
process which gives the only target products.
Scheme 2. Reaction with Different Proportions of TEMPO/1b
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4Å MS, N2
N
N
N
O
+
+
2b
dioaxne, 80 o
24 h
C
O
O2SN3
2b'
TEMPO
1b
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In an attempt to understand the mechanism, a mixture of 1,1ꢀdibenzylhydrazine (3)
and diacetoxyiodobenzene (PhI(OAc)2) was subjected to the standard reaction
conditions (Scheme 3). The coupling product was formed in 95% yield compared to
92% in the reaction using 1b as the substrate (Table 2). More interestingly, the yield
and ratio of products 2b and 2b′ (yield 93%，2b/2b′ = 65/35) in a radical trapping
experiment using 3 and PhI(OAc)2 as the substrates was also similar to the results
from the reaction in which 1b was the starting material (yield 99%，2b/2b′ = 62/38,
see Scheme 2). Since it’s known that 1,1ꢀdiazenes are the reactive intermediates in the
oxidation of 1,1ꢀdisubstituted hydrazines to form C–C bonds,14,15 the thermal
degradation of sulfamoyl azides may proceed via a 1,1ꢀdiazene intermediate.
Scheme 3. Using 1,1ꢀBibenzylhydrazine (3) with PhI(OAc)2 as Substrates
When the cyclopropylmethylꢀcontaining sulfamoyl azide (1z) was subjected to the
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reaction conditions, the desired product (2z) was isolated in 55% yield without
ringꢀopening products (Scheme 1, eq 4). This result shows that it is difficult to form a
free alkyl radical in this reaction system.
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Scheme 4. Possible Mechanisms of Thermal Rearrangement of Sulfamoyl Azides
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Based on these results, possible mechanisms are proposed in Scheme 4. First, the
sulfamoyl azide goes through a Curtiusꢀtype rearrangement, then it releases a
molecule of sulfur dioxide and nitrogen, and is converted into a 1,1ꢀdiazene
intermediate. Subsequently, the 1,1ꢀdiazene is converted into the target product by
means of a rearrangement process (path a, the major pathway). Alternatively, the
1,1ꢀdiazene is transferred to the target product and crossover coupling products by a
free radical process (path b, the minor pathway). Although the rearrangement process
(path a) is hard to believe, we can't come up with a more precedented mechanism that
still explains all the data.
Complex molecules such as sterols are tolerated in these reaction conditions (Table
4). For example, both the stigmasterol derivative (5a) and cholesterol derivative (5b)
were obtained in good yield in the optimized reaction conditions. We also
successfully applied this method to the synthesis of some bioactive compounds 5c and
5d, which were reported to be synthesized by the hydrolysis of piperine to piperic
acid followed by reduction and the reaction with amino acid methyl esters, and have
shown better antileishmanial activity than either piperine or the amino acid methyl
esters.16
Table 4. Applications in the Synthesis of Complex Molecules. a,b
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a
The optimized conditions: sulfamoyl azide 4 (0.2 mmol), 4Å MS (50 mg) and
dioxane (2 mL), 80 oC , under nitrogen, 24 h. b Isolated yields.
In conclusion, we have developed the rearrangement of sulfamoyl azides under
mild reaction conditions. The reaction has broad substrate range and high functional
group tolerance. Mechanism studies suggested that Curtiusꢀtype rearrangement of
sulfamoyl azide proceeds via a 1,1ꢀdiazene. The subsequent rearrangement proceeds
by both a concerted process and a free radical process forming a new CꢀC bond, and
the concerted process predominates. The reaction can be applied to the synthesis of
some biologically active molecules such as sterol and piperine derivatives. A major
limitation of this reaction is that one benzyl substituent group on the nitrogen atom is
necessary. Efforts directed to the development of variants of the reaction and detailed
studies to elucidate the mechanism underlying the unique reactivity of sulfamoyl
azides are in progress.
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Experimental Section
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General. Unless otherwise mentioned, all commercial reagents and solvents were used without
further purification. Thin layer chromatography (TLC) was performed on preꢀcoated silica gel
GF254 plates. Visualization of TLC was achieved by the use of UV light (254 nm). Column
chromatography was performed on silica gel (300ꢀ400 mesh) using a proper eluent. 1H NMR was
recorded on FT AM 400 (400 MHz). Chemical shifts were reported in parts per million (ppm)
referenced to the appropriate solvent peak or 0.0 ppm for tetramethylsilane. The following
abbreviations were used to describe peak splitting patterns: br = broad, s = singlet, d = doublet, t =
triplet, q = quartet, dd = doublet of doublet, td = triplet of doublet, ddd = doublet of doublet of
doublet, m = multiplet. Coupling constants, J, were reported in hertz (Hz). The fully decoupled
13C NMR was recorded on FT AM 400 (100 MHz). Chemical shifts were reported in ppm
referenced to the center of a triplet at 77.0 ppm of chloroformꢀd. Infrared (IR) spectra were
recorded neat in KBr cell. Frequencies are given in centimeter inverse (cmꢀ1) and only selected
absorbance is reported. High resolution mass spectra were obtained by using the UHD
AccurateꢀMass QꢀTOF. Compound 3 is a known compound and was prepared according to the
reference.17
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General procedure for the synthesis of sulfamoyl azide１and 4. A solution of amine (454 mg,
2.0 mmol) and DBU (456 mg, 3.0 mmol) in DCM (10 mL) was added to the solution of N3SO2N3
(4.0 mmol, prepared according to the reference12b) in DCM. After the reaction mixture was stirred
for 2 h, water (15 mL) was added and the aqueous solution was extracted with EA (3 x 20 mL).
The combined organic layer was dried over Na2SO4 and concentrated under reduced pressure. The
crude product was purified by short pad of silica gel column using Petroleum Ether (PE) and Ethyl
Acetate (EA) as eluent. Note: Some azides could be explosive and should be handled carefully.
Based on DSC experiments,11 this type of azide is stable under the reaction conditions used.
1ꢀ(((Azidosulfonyl)(benzyl)amino)methyl)ꢀ4ꢀmethoxybenzene (1a)．Column chromatography
(PE/EA 50/1) afforded 1a as a white solid (452 mg, 68%). TLC: Rf = 0.70 (PE/EA = 10/1). 1H
NMR (400 MHz, CDCl3) δ 7.45 – 7.32 (m, 5H), 7.25 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 8.5 Hz, 2H),
4.40 (s, 2H), 4.36 (s, 2H), 3.82 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 159.5, 134.1, 130.1, 128.6,
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128.5, 128.2, 125.7, 113.9, 55.0, 50.7, 50.5. IR (KBr): 2127, 1540, 1514, 1383, 1275, 1260, 1165,
1032, 749, 668 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C15H16N4O3S 333.1016, found
333.1023.
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(((Azidosulfonyl)(benzyl)amino)methyl)benzene (1b)．Column chromatography (PE/EA 50/1)
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1
afforded 1b as a white solid (501 mg, 83%). Rf = 0.80 (PE/EA = 10/1). H NMR (400 MHz,
CDCl3) δ 7.50 – 7.30 (m, 10H), 4.45 (s, 4H). 13C NMR (101 MHz, CDCl3) δ 134.0, 128.64,
128.63, 128.2, 51.1. IR (KBr): 2127, 1568, 1540, 1496, 1456, 1382, 1206, 1167, 1091, 1055,
1029, 897, 786, 740, 668, 605 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C14H14N4O2S 303.0910,
found 303.0899.
1ꢀ(((Azidosulfonyl)(4ꢀmethoxybenzyl)amino)methyl)ꢀ4ꢀmethoxybenzene (1c) ． Column
chromatography (PE/EA 10/1) afforded 1c as a white solid (478 mg, 66%). TLC: Rf = 0.25(PE/EA
= 10/1). 1H NMR (400 MHz, CDCl3) δ 7.23 – 7.18 (m, 4H), 6.95 – 6.84 (m, 4H), 4.31 (s, 4H),
3.82 (s, 6H). 13C NMR (101 MHz, CDCl3) δ 159.7, 130.3, 126.1, 114.2, 55.3, 50.3. IR (KBr):
2936, 2838, 2128, 1612, 1586, 1514, 1463, 1379, 1304, 1252, 1165, 1111, 1064, 1033, 907, 822,
751, 668, 605, 524 cmꢀ1; HRMS (APCI) ([MꢀH]ꢀ) Calcd. for C16H18N4O4S 361.0976, found
361.0987.
2ꢀ(((Azidosulfonyl)(4ꢀmethoxybenzyl)amino)methyl)naphthalene
(1d)
．
Column
chromatography (PE/EA 10/1) afforded 1d as a white solid (520 mg, 68%). TLC: Rf = 0.70
1
(PE/EA = 5/1). H NMR (400 MHz, CDCl3 ) δ 8.19 – 8.05 (m, 1H), 7.97 – 7.82 (m, 2H), 7.67 –
7.44 (m, 4H), 7.17 – 7.05 (m, 2H), 6.89 – 6.71 (m, 2H), 4.95 (s, 2H), 4.37 (s, 2H), 3.78 (s, 3H).
13C NMR (101 MHz, CDCl3 ) δ 159.3, 133.7, 131.4, 129.9, 129.3, 128.6, 127.5, 126.6, 126.0,
125.9, 124.9, 123.1, 113.8, 55.0, 51.0, 49.6. IR (KBr): 2128, 1611, 1513, 1380, 1249, 1207, 1166,
1035, 900, 793, 770, 668, 605 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C19H18N4O3S 383.1173,
found 383.1161.
1ꢀ(((Azidosulfonyl)(4ꢀfluorobenzyl)amino)methyl)ꢀ4ꢀmethoxybenzene
(1e)
．
Column
chromatography (PE/EA 10/1) afforded 1e as a colorless oil (560 mg, 80%). TLC: Rf = 0.25
(PE/EA = 10/1). 1H NMR (400 MHz, CDCl3) δ 7.27 – 7.22 (m, 2H), 7.22 – 7.17 (m, 2H), 7.08 –
7.01 (m, 2H), 6.92 – 6.86 (m, 2H), 4.33 (s, 2H), 4.32 (s, 2H), 3.82 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ 162.68 (d, J = 247.5 Hz), 159.8, 130.5 (d, J = 8.2 Hz), 130.3, 130.1 (d, J = 3.2 Hz),
125.8, 115.8 (d, J = 21.6 Hz), 114.3, 55.3, 50.8, 50.2. 19F NMR (376 MHz, CDCl3) δ ꢀ113.37. IR
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(neat): 2936, 2839, 2128, 1611, 1512, 1457, 1380, 1253, 1207, 1167, 1112, 1065, 1034, 909, 827,
778, 754, 668, 606 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C15H15FN4O3S 351.0922, found
351.0918.
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1ꢀ(((Azidosulfonyl)(4ꢀchlorobenzyl)amino)methyl)ꢀ4ꢀmethoxybenzene
(1f)
．
Column
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chromatography (PE/EA 30/1) afforded 1f as a colorless oil (586 mg, 80%). TLC: Rf = 0.85
(PE/EA = 10/1). 1H NMR (400 MHz, CDCl3) δ 7.38 – 7.29 (m, 2H), 7.20 (dd, J = 8.3, 6.8 Hz,
4H), 6.89 (d, J = 8.7 Hz, 2H), 4.32 (s, 4H), 3.82 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 159.8,
134.3, 132.9, 130.3, 130.1, 129.0, 125.7, 114.3, 55.3, 51.0, 50.3. IR (neat): 2128, 1612, 1514,
1382, 1253, 1166, 909, 604 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C15H15ClN4O3S 367.0626,
found 367.0628.
1ꢀ(((Azidosulfonyl)(4ꢀbromobenzyl)amino)methyl)ꢀ4ꢀmethoxybenzene
(1g).
Column
chromatography (PE/EA 30/1) afforded 1g as a white solid (658 mg, 80%). TLC: Rf =
0.75(PE/EA = 10/1).1H NMR (400 MHz, CDCl3) δ 7.55 – 7.44 (m, 2H), 7.21 – 7.08 (m, 4H), 6.93
– 6.81 (m, 2H), 4.32 (s, 2H), 4.31 (s, 2H), 3.82 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 159.8,
133.4, 132.0, 130.4, 130.3, 125.6, 122.4, 114.3, 55.3, 51.0, 50.3. IR (KBr): 2128, 1611, 1514,
1382, 1253, 1165, 909, 602 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C15H15BrN4O3S 411.0121,
found 411.0104.
1ꢀ(((Azidosulfonyl)(4ꢀcyanobenzyl)amino)methyl)ꢀ4ꢀmethoxybenzene
(1h)
．
Column
chromatography (PE/EA 5/1) afforded 1h as a yellow solid (564 mg, 79%). TLC: Rf = 0.35
(PE/EA = 5/1). 1H NMR (400 MHz, CDCl3) δ 6.30 (d, J = 8.2 Hz, 2H), 6.06 (d, J = 8.2 Hz, 2H),
5.88 (d, J = 8.6 Hz, 2H), 5.56 (d, J = 8.6 Hz, 2H), 3.12 (s, 2H), 3.07 (s, 2H), 2.49 (s, 4H). 13C
NMR (101 MHz, CDCl3) δ 159.6, 139.9, 132.1, 130.1, 128.7, 125.0, 118.1, 114.0, 111.6, 54.9,
51.7, 50.5. IR (KBr): 2227, 2130, 1669, 1540, 1514, 1384, 1257, 1165, 1105, 1032, 909, 821, 749,
668 cmꢀ1; HRMS (APCI) ([MꢀH]ꢀ) Calcd. for C16H15N5O3S 356.0823, found 356.0813．
1ꢀ(((Azidosulfonyl)(4ꢀmethoxybenzyl)amino)methyl)ꢀ4ꢀnitrobenzene
(1i)
．
Column
chromatography (PE/EA 10/1) afforded 1i as a yellow solid (445 mg, 59%). TLC: Rf = 0.80
(PE/EA =2/1). 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 2H), 7.40 (d, J = 8.6 Hz, 2H),
7.17 (d, J = 8.6 Hz, 2H), 6.93 – 6.77 (m, 2H), 4.44 (s, 2H), 4.37 (s, 2H), 3.81 (s, 3H). 13C NMR
(101 MHz, CDCl3) δ 160.0, 147.8, 142.1, 130.4, 129.2, 125.2, 123.9, 114.4, 55.3, 52.0, 50.5. IR
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(KBr): 2131, 1610, 1514, 1382, 1347, 1256, 1166, 1109, 1067, 1032, 912, 849, 750, 693, 668, 605
cmꢀ1; HRMS (APCI) ([MꢀH]ꢀ) Calcd. for C15H15N5O5S 376.0721, found 376.0729.
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1ꢀ(((Azidosulfonyl)(4ꢀmethoxybenzyl)amino)methyl)ꢀ3,5ꢀbis(trifluoromethyl)benzene
(1j).
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Column chromatography (PE/EA 30/1) afforded 1j as a white solid (692 mg, 74%). TLC: Rf =
0.85 (PE/EA = 10/1). 1H NMR (400 MHz, CDCl3) δ 7.77 (s, 1H), 7.56 (s, 2H), 7.13 (d, J = 8.6 Hz,
2H), 6.88 – 6.78 (m, 2H), 4.46 (s, 2H), 4.39 (s, 2H), 3.79 (s, 3H). 13C NMR (101 MHz, CDCl3) δ
160.1, 137.6, 132.0 (q, J = 33.6 Hz), 130.5, 128.58 (d, J = 2.5 Hz), 125.0, 122.99 (d, J = 272.9
Hz), 122.54 – 121.85 (m), 114.4, 55.2, 52.9, 50.9. 19F NMR (376 MHz, CDCl3) δ ꢀ62.96. IR
(KBr): 2939, 2842, 2385, 2131, 1613, 1586, 1515, 1466, 1382, 1286, 1180, 1070, 1035, 906, 753,
605 cmꢀ1; HRMS (APCI) ([MꢀH]ꢀ) Calcd. for C17H14F6N4O3S 467.0618, found 467.0615.
(2ꢀ(((Azidosulfonyl)(4ꢀmethoxybenzyl)amino)methyl)phenyl)(tertꢀbutyl)sulfane
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(1k)． Column chromatography (PE/EA 20/1) afforded 1k as a white solid (790 mg, 94%). TLC:
Rf = 0.65 (PE/EA = 10/1). 1H NMR (400 MHz, CDCl3) δ 7.60 – 7.50 (m, 2H), 7.39 (dt, J = 7.7,
3.8 Hz, 1H), 7.30 – 7.24 (m, 2H), 7.19 (d, J = 8.6 Hz, 2H), 6.82 (d, J = 8.7 Hz, 2H), 4.82 (s, 2H),
4.35 (s, 2H), 3.79 (s, 3H), 1.23 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 159.6, 140.0, 139.2, 131.9,
130.5, 129.6, 128.9, 127.8, 126.2, 114.1, 55.3, 52.0, 50.1, 47.8, 30.9. IR (KBr): 2962, 2127, 1611,
1514, 1458, 1382, 1304, 1252, 1167, 912, 822, 668 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for
C19H24N4O3S2 421.1363, found 421.1360.
1ꢀ(((Azidosulfonyl)(1ꢀphenylethyl)amino)methyl)ꢀ4ꢀmethoxybenzene
(1l)
．
Column
chromatography (PE/EA 20/1) afforded 1l as a white solid (311 mg, 45%). TLC: Rf = 0.70 (PE/EA
= 10/1). 1H NMR (400 MHz, CDCl3) δ 7.47 – 7.30 (m, 5H), 7.07 (d, J = 8.7 Hz, 2H), 6.90 – 6.69
(m, 2H), 5.25 (q, J = 7.1 Hz, 1H), 4.39 (d, J = 15.5 Hz, 1H), 4.14 (d, J = 15.5 Hz, 1H), 3.79 (s,
3H), 1.59 (d, J = 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 159.2, 138.1, 129.6, 128.6, 128.3,
127.94, 127.9, 113.7, 58.4, 55.1, 48.8, 17.7. IR (KBr): 2385, 2316, 2125, 1613, 1514, 1454, 1384,
1249, 1207, 1170, 1103, 1033, 888, 823, 785, 740, 698, 668, 592 cmꢀ1; HRMS (APCI) ([M+H]+)
Calcd. for C16H18N4O3S 347.1173, found 347.1176.
2ꢀ(((Azidosulfonyl)(benzyl)amino)methyl)pyridine (1m) ．Column chromatography (PE/EA
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10/1) afforded 1m as a yellow solid (509 mg, 84%). TLC: Rf = 0.40 (PE/EA = 10/1). H NMR
(400 MHz, CDCl3) δ 8.61 (dd, J = 4.1, 1.5 Hz, 1H), 7.66 (td, J = 7.7, 1.6 Hz, 1H), 7.41 – 7.28 (m,
5H), 7.28 – 7.18 (m, 2H), 4.54 (s, 2H), 4.50 (s, 2H). 13C NMR (101 MHz, CDCl3) δ 154.6, 149.5,
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136.8, 134.2, 128.7, 128.6, 128.2, 122.8, 122.7, 52.3, 51.9. IR (KBr): 2129, 1541, 1434, 1382,
1262, 1165, 1058, 792, 741, 698, 668 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C13H13N5O2S
304.0863, found 304.0860.
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2ꢀ(((Azidosulfonyl)(4ꢀnitrobenzyl)amino)methyl)furan (1n)．Column chromatography (PE/EA
10/1) afforded 1n as a brown solid (303 mg, 45%). TLC: Rf = 0.50 (PE/EA = 10/1). 1H NMR (400
MHz, CDCl3) δ 8.22 (d, J = 8.7 Hz, 2H), 7.51 (d, J = 8.7 Hz, 2H), 7.44 (d, J = 1.1 Hz, 1H), 6.39 –
6.36 (m, 1H), 6.35 (d, J = 3.2 Hz, 1H), 4.53 (s, 2H), 4.40 (s, 2H). 13C NMR (101 MHz, CDCl3) δ
147.9, 147.4, 143.7, 141.9, 129.1, 123.9, 111.1, 110.8, 50.8, 44.5. IR (KBr): 2134, 1522, 1385,
1348, 1167, 1109, 1058, 1014, 921, 776, 739, 668, 599 cmꢀ1; HRMS (APCI) ([MꢀH]ꢀ) Calcd. for
C12H11N5O5S 336.0408, found 336.0388.
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2ꢀ(((Azidosulfonyl)(thiophenꢀ2ꢀylmethyl)amino)methyl)thiophene
(1o)
．
Column
chromatography (PE/EA 20/1) afforded 1o as a yellow solid (358 mg, 57%). TLC: Rf = 0.65
(PE/EA = 10/1). 1H NMR (400 MHz, CDCl3) δ 7.36 (dd, J = 5.1, 1.1 Hz, 2H), 7.09 (d, J = 3.3 Hz,
2H), 7.02 (dd, J = 5.1, 3.5 Hz, 2H), 4.63 (s, 4H). 13C NMR (101 MHz, CDCl3) δ 136.1, 128.8,
127.2, 127.1, 45.4. IR (KBr): 2130, 1540, 1436, 1385, 1276, 1234, 1104, 1034, 903, 838, 770,
707, 668, 591, 526 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C10H10N4O2S3 315.0039, found
315.0032.
2ꢀ(((azidosulfonyl)(furanꢀ2ꢀylmethyl)amino)methyl)furan (1p) ． Column chromatography
(PE/EA 10/1) afforded 1p as a brown solid (418 mg, 74%). TLC: Rf = 0.30 (PE/EA = 10/1). 1H
NMR (400 MHz, CDCl3) δ 7.45 (dd, J = 1.7, 0.8 Hz, 2H), 6.44 – 6.35 (m, 4H), 4.45 (s, 4H). 13C
NMR (101 MHz, CDCl3) δ 148.0, 143.5, 110.7, 110.6, 44.1. IR (KBr): 2134, 1504, 1433, 1386,
1344, 1168, 1109, 1012, 932, 884, 820, 745, 668, 598, 539 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd.
for C10H10N4O4S 283.0496 found (283.0487).
(((Azidosulfonyl)(cyclopentyl)amino)methyl)benzene (1q)．Column chromatography (PE/EA
10/1) afforded 1q as a yellow oil (347 mg, 62%). TLC: Rf = 0.45 (PE/EA = 10/1). 1H NMR (400
MHz, CDCl3) δ 7.40 – 7.33 (m, 4H), 7.32 – 7.26 (m, 1H), 4.43 (s, 2H), 4.31 – 4.18 (m, 1H), 1.97 –
1.82 (m, 2H), 1.73 – 1.47 (m, 6H). 13C NMR (101 MHz, CDCl3) δ 137.0, 128.6, 127.6, 126.8,
61.2, 49.0, 29.3, 23.30. IR (neat): 2961, 2124, 1454, 1378, 1208, 1164, 1105, 1056, 1028, 860,
804, 734, 96, 668, 601 cmꢀ1; HRMS (APCI) ([MꢀH]ꢀ) Calcd. for C12H16N4O2S 279.0921, found
279.0908.
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1ꢀ(((Azidosulfonyl)(cyclopentyl)amino)methyl)ꢀ4ꢀmethoxybenzene
(1r)
．
Column
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chromatography (PE/EA 20/1) afforded 1r as a colorless oil (354 mg, 57%). Rf = 0.65 (PE/EA =
10/1). 1H NMR (400 MHz, CDCl3) δ 7.25 (d, J = 8.7 Hz, 2H), 6.85 (d, J = 8.7 Hz, 2H), 4.35 (s,
2H), 4.17 (dt, J = 23.7, 9.5 Hz, 1H), 3.77 (s, 3H), 1.91 – 1.75 (m, 2H), 1.69 – 1.46 (m, 6H). 13C
NMR (101 MHz, CDCl3) δ 159.0, 128.8, 128.2, 113.9, 61.1, 55.1, 48.7, 29.2, 23.2. IR (neat):
2959, 2874, 1614, 1586, 1514, 1455, 1378, 1248, 1209, 1163, 1111, 1035, 948, 866, 819, 734,
668, 601 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C13H18N4O3S 311.1173, found 311.1157.
1ꢀ(((Azidosulfonyl)(cyclopentyl)amino)methyl)ꢀ4ꢀnitrobenzene (1s)．Column chromatography
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(PE/EA 20/1) afforded 1s as a colorless oil (433 mg, 67%). TLC: Rf = 0.60 (PE/EA = 10/1). H
NMR (400 MHz, CDCl3) δ 8.21 (d, J = 8.6 Hz, 2H), 7.52 (d, J = 8.6 Hz, 2H), 4.47 (s, 2H), 4.37 –
4.24 (m, 1H), 1.99 – 1.87 (m, 2H), 1.73 – 1.44 (m, 6H). 13C NMR (101 MHz, CDCl3) δ 147.5,
144.7, 127.5, 123.9, 61.2, 48.0, 29.3, 23.3. IR (neat): 2128, 1602, 1523, 1378, 1346, 1026, 1164,
1109, 1060, 860, 796, 736, 668, 600 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C12H15N5O4S
326.0918, found 326.0908.
1ꢀ(((Azidosulfonyl)(2,2,2ꢀtrifluoroethyl)amino)methyl)ꢀ4ꢀmethoxybenzene (1t) ． Column
chromatography (PE/EA 30/1) afforded 1t as a white solid (246 mg, 38%). TLC: Rf = 0.85
(PE/EA = 10/1). 1H NMR (400 MHz, CDCl3) δ 7.32 – 7.25 (m, 2H), 6.97 – 6.88 (m, 2H), 4.57 (s,
2H), 3.82 (s, 3H), 3.76 (q, J = 8.7 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 160.2, 130.4, 124.5,
123.71 (q, J = 281.1 Hz), 114.5, 55.2, 52.2 , 46.82 (q, J = 35.0 Hz). 19F NMR (376 MHz, CDCl3) δ
ꢀ69.11. IR (KBr): 2136, 1613, 1515, 1386, 1268, 1251, 1038, 787, 667 cmꢀ1; HRMS (APCI)
([M+H]+) Calcd. for C10H11F3N4O3S 325.0577, found 325.0565.
3ꢀ(2ꢀ((Azidosulfonyl)(benzyl)amino)ethyl)ꢀ1ꢀtosylꢀ1Hꢀindole (1u). Column chromatography
(PE/EA 10/1) afforded 1u as a yellow solid (573 mg, 75% (from 1.5 mmol of amine)). TLC: Rf =
0.50 (PE/EA = 5/1). 1H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 8.3 Hz, 1H), 7.77 (d, J = 8.4 Hz,
2H), 7.40 – 7.30 (m, 5H), 7.29 – 7.26 (m, 2H), 7.25 – 7.16 (m, 4H), 4.40 (s, 2H), 3.50 (dd, J = 8.9,
6.7 Hz, 2H), 3.01 – 2.84 (m, 2H), 2.30 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 144.8, 135.0,
134.2, 130.1, 129.7, 128.8, 128.42, 128.4, 126.6, 124.7, 123.6, 123.1, 119.0, 118.3, 113.6, 53.2,
48.2, 23.9, 21.3. IR (KBr): 2127, 1541, 1447, 1374, 1171, 1121, 1089, 1020, 812, 744,702, 668,
573 cmꢀ1; HRMS (ESI) ([MꢀH]ꢀ) Calcd. for C24H23N5O4S2 508.1118, found 508.1122.
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Ethyl Nꢀ(azidosulfonyl)ꢀNꢀ(thiophenꢀ2ꢀylmethyl)glycinate (1v) ．Column chromatography
(PE/EA 10/1) afforded 1v as a brown oil (462 mg, 76%).TLC: Rf = 0.60 (PE/EA = 5/1).1H NMR
(400 MHz, CDCl3) δ 7.31 (dd, J = 5.1, 1.0 Hz, 1H), 7.01 (d, J = 3.3 Hz, 1H), 6.96 (dd, J = 5.0, 3.5
Hz, 1H), 4.79 (s, 2H), 4.21 (q, J = 7.1 Hz, 2H), 4.01 (s, 2H), 1.26 (t, J = 7.1 Hz, 3H). 13C NMR
(101 MHz, CDCl3) δ 167.9, 135.7, 128.6, 127.1, 126.9, 61.7, 47.7, 47.0, 13.8. IR (neat): 2985,
2134, 1747, 1386, 1216, 1165, 1083, 1023, 783, 709, 668, 604, 526 cmꢀ1; HRMS (APCI) ([MꢀH]ꢀ)
Calcd. for C9H12N4O4S2 303.0227, found 303.0238.
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Ethyl Nꢀ(azidosulfonyl)ꢀNꢀ(4ꢀmethoxybenzyl)leucinate (1w)．Column chromatography (PE/EA
20/1) afforded 1w as a colorless oil (300 mg, 39%). TLC: Rf = 0.40 (PE/EA = 20/1).1H NMR (400
MHz, CDCl3) δ 7.30 (d, J = 8.6 Hz, 2H), 6.84 (d, J = 8.7 Hz, 2H), 4.64 (d, J = 15.8 Hz, 1H), 4.49
(t, J = 7.5 Hz, 1H), 4.41 (d, J = 15.8 Hz, 1H), 4.24 – 4.07 (m, 2H), 3.77 (s, 3H), 1.61 (t, J = 7.2
Hz, 2H), 1.52 – 1.38 (m, 1H), 1.27 (t, J = 7.1 Hz, 3H), 0.83 (d, J = 6.5 Hz, 3H), 0.64 (d, J = 6.6
Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 170.4, 159.4, 129.9, 127.6, 113.8, 61.7, 59.9, 55.2, 50.5,
38.5, 24.2, 22.3, 21.1, 13.9. IR (neat): 2960, 2130, 1742, 1613, 1515, 1386, 1250, 1203, 1171,
1107, 1035, 877, 821, 748, 668, 604 cmꢀ1; HRMS (APCI) ([MꢀH]ꢀ) Calcd. for C16H24N4O5S
383.1394, found 383.1389.
Ethyl Nꢀ(azidosulfonyl)ꢀNꢀ(4ꢀmethoxybenzyl)phenylalaninate (1x). Column chromatography
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(PE/EA 10/1) afforded 1x as a yellow oil (343 mg, 41%). TLC: Rf = 0.50 (PE/EA = 10/1). H
NMR (400 MHz, CDCl3) δ 7.30 – 7.21 (m, 3H), 7.19 (d, J = 8.5 Hz, 2H), 7.09 (d, J = 7.5 Hz, 2H),
6.83 (d, J = 8.6 Hz, 2H), 4.61 – 4.47 (m, 2H), 4.31 (d, J = 15.4 Hz, 1H), 4.20 – 3.99 (m, 2H), 3.80
(s, 3H), 3.28 (dd, J = 14.2, 7.3 Hz, 1H), 3.02 (dd, J = 14.2, 7.9 Hz, 1H), 1.21 (t, J = 7.1 Hz, 3H).
13C NMR (101 MHz, CDCl3) δ 169.3, 159.5, 136.3, 130.1, 129.1, 128.4, 126.9, 126.7, 113.9, 62.7,
61.9, 55.2, 51.4, 36.4, 13.8. IR (neat): 2936, 2837, 2130, 1732, 1612, 1514, 1455, 1386, 1248,
1167, 1130, 1109, 1033, 832, 747, 700, 668, 605 cmꢀ1; HRMS (APCI) ([MꢀH]ꢀ) Calcd. for
C19H22N4O5S 417.1238, found 417.1229.
1ꢀ(((azidosulfonyl)(tertꢀbutyl)amino)methyl)ꢀ4ꢀmethoxybenzene (1y)． To a stirred solution of
the NꢀtertꢀbutylꢀNꢀ4ꢀmethoxybenzyl sulfamide (272 mg, 1.0 mmol, which was prepared according
to the reference18a) in DCM (15 mL) under N2 was added DBU (228 mg, 1.5 mmol). The above
triflyl azide solution (3.3 mL, 2.0 mmol, obtained according to the reference12b) in hexane was
then added dropwise over 5 min. The reaction mixture was stirred at room temperature for 24 h,
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after which the solvent blew away by the air flow. Purification of the crude residue by flash
chromatography on silica gel (CHCl3) afforded the product as a colorless oil (206 mg, 69%). TLC:
Rf = 0.40 (PE/EA = 10/1). 1H NMR (400 MHz, CDCl3) δ 7.28 (d, J = 8.7 Hz, 2H), 6.88 (d, J = 8.7
Hz, 2H), 4.54 (s, 2H), 3.80 (s, 3H), 1.44 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 158.9, 130.1,
127.9, 114.0, 61.8, 55.3, 50.6, 29.7. IR (neat): 2961, 2124, 1544, 1497, 1379, 1208, 1164, 1056,
945, 861, 735, 696, 668, 602, 542 cmꢀ1; HRMS (APCI) ([MꢀH]ꢀ) Calcd. for C12H18N4O3S
297.1027, found 297.1022.
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1ꢀ(((Azidosulfonyl)(cyclopropylmethyl)amino)methyl)ꢀ4ꢀmethoxybenzene (1z) ． Column
chromatography (PE/EA 10/1) afforded 1z as a colorless oil (438 mg, 74%). TLC: Rf = 0.50
(PE/EA = 10/1). 1H NMR (400 MHz, CDCl3) δ 7.38 – 7.18 (m, 2H), 6.98 – 6.80 (m, 2H), 4.51 (s,
2H), 3.81 (s, 3H), 3.10 (d, J = 7.0 Hz, 2H), 1.05 – 0.91 (m, 1H), 0.61 – 0.50 (m, 2H), 0.18 (q, J =
4.9 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 159.6, 129.7, 126.7, 114.2, 55.3, 52.7, 51.5, 8.7, 4.0.
IR (neat): 2126, 1613, 1514, 1379, 1249, 1162, 1105, 1034, 910, 801, 751, 668, 601 cmꢀ1; HRMS
(APCI) ([M+H]+) Calcd. for C12H16N4O3S 297.1016, found 297.1014.
(3S,8S,9S,10R,13R,14S,17R)ꢀ3ꢀ((Azidosulfonyl)(4ꢀbromobenzyl)amino)ꢀ17ꢀ((2R,5S,E)ꢀ5ꢀet
hylꢀ6ꢀmethylheptꢀ3ꢀenꢀ2ꢀyl)ꢀ10,13ꢀdimethylꢀ2,3,4,7,8,9,10,11,12,13,14,15,16,17ꢀtetradecahydr
oꢀ1Hꢀcyclopenta[a]phenanthrene (4a). 3βꢀAzidoꢀ5ꢀstigmastene (2.0 g, 4.6 mmol), which was
obtained in 72% yield from commercial available stigmasterol according to the reference,18b,c
was dissolved into anhydrous THF (40 mL) at 0 oC. After LiAlH4 (260 mg, 6.8 mmol) was added
to this solution, the reaction mixture was slowly warmed to room temperature and stirred
overnight. The reaction was quenched by slowly addition of iceꢀcold water, and then the mixture
was filtrated and concentrated under reduced pressure to afford crude 3βꢀaminoꢀ5ꢀstigmastene
(1.292 g) as a white solid, which was used directly for next step. The crude
3βꢀaminoꢀ5ꢀstigmastene (930 mg) was dissolved into DCM (30 mL) at room temperature,
followed by the addition of 4ꢀbromobenzaldehyde (610 mg, 3.3 mmol) and Na2SO4 (625 mg 4.4
mmol). The reaction mixture was stirred overnight. Upon completion, the mixture was
concentrated under reduced pressure. MeOH (40 mL) and NaBH4 (0.251 g) was added to the
concentrate and the mixture continued stirring for additional 2 h. The water (30 mL) was added
and extracted with EtOAc (3 x 30 mL). The combined organic layer was dried over Na2SO4 and
concentrated under reduced pressure. The crude product was purified by short pad of silica gel
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column using Petroleum Ether (PE) and Ethyl Acetate (EA) as eluent to form
3βꢀ(4ꢀbromobenzyl)aminoꢀ5ꢀstigmastene as a white solid (0.665 g, 36% (3 steps)). The synthesis
of compound 4a from 3βꢀ(4ꢀbromobenzyl)aminoꢀ5ꢀstigmastene was according to the general
procedure for the synthesis of sulfamoyl azides 1 and 4. Column chromatography (PE/EA 20/1)
afforded 4a as a white solid (391 mg (from 1.0 mmol of amine), 57%). TLC: Rf = 0.65 (PE/EA =
10/1). 1H NMR (400 MHz, CDCl3) δ 7.48 (d, J = 8.3 Hz, 2H), 7.26 (d, J = 7.9 Hz, 2H), 5.33 (d, J
= 4.0 Hz, 1H), 5.15 (dd, J = 15.1, 8.5 Hz, 1H), 5.01 (dd, J = 15.1, 8.6 Hz, 1H), 4.49 – 4.36 (m,
2H), 3.72 – 3.57 (m, 1H), 2.43 (t, J = 12.2 Hz, 1H), 2.13 (dd, J = 13.1, 3.2 Hz, 1H), 2.08 – 1.90
(m, 3H), 1.86 (d, J = 13.3 Hz, 1H), 1.77 – 1.64 (m, 3H), 1.53 – 0.76 (m, 31H), 0.68 (s, 3H). 13C
NMR (101 MHz, CDCl3) δ 139.6, 138.2, 136.0, 131.8, 129.32, 129.26, 122.8, 121.9, 61.3, 56.7,
55.9, 51.2, 49.9, 48.8, 42.2, 40.4, 39.5, 38.0, 36.8, 36.5, 31.9, 31.8, 28.9, 26.9, 25.4, 24.3, 21.2,
21.1, 20.9, 19.3, 18.9, 12.2, 12.0. IR (KBr): 2131, 1540, 1261, 802, 750, 668 cmꢀ1; HRMS (APCI)
([M+H]+) Calcd. for C36H53BrN4O2S 685.3146, found 685.3150.
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(3S,8S,9S,10R,13R,14S,17R)ꢀ3ꢀ((azidosulfonyl)(4ꢀnitrobenzyl)amino)ꢀ17ꢀ((2R,5S,E)ꢀ5ꢀethylꢀ6
ꢀmethylheptꢀ3ꢀenꢀ2ꢀyl)ꢀ10,13ꢀdimethylꢀ2,3,4,7,8,9,10,11,12,13,14,15,16,17ꢀtetradecahydroꢀ1H
ꢀcyclopenta[a]phenanthrene (4b). The synthesis of compound 4b from commercial available
cholesterol
was
according
to
the
procedure
for
the
synthesis
of
4a.
3βꢀ(4ꢀNitrobenzyl)aminoꢀ5ꢀcholestene was obtained in 46% yield (0.869 g, 3 steps), white solid.
1H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 7.9 Hz, 2H), 7.50 (d, J = 7.9 Hz, 2H), 5.31 (s, 1H),
3.92 (s, 2H), 2.44 (s, 1H), 2.26 (d, J = 12.2 Hz, 1H), 2.11 (t, J = 11.8 Hz, 1H), 1.98 (t, J = 15.9 Hz,
2H), 1.83 (t, J = 11.4 Hz, 3H), 1.63 – 1.29 (m, 12H), 1.19 – 1.04 (m, 7H), 1.00 (s, 5H), 0.89 (dd, J
= 20.6, 5.8 Hz, 10H), 0.67 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 148.9, 146.9, 141.3, 128.5,
123.5, 121.0, 58.0, 56.8, 56.2, 50.3 (d, J = 5.9 Hz), 42.3, 40.2, 39.8, 39.5, 38.0, 37.1, 36.2, 35.8,
31.9 (d, J = 2.7 Hz), 29.6, 28.3, 28.0, 24.3, 23.9, 22.8, 22.6, 21.0, 19.5, 18.7, 11.9. Column
chromatography (PE/EA 5/1) afforded 4b as a white solid. (326 mg (from 1.0 mmol of amine),
52%). TLC: Rf = 0.75 (PE/EA = 2/1). 1H NMR (400 MHz, CDCl3) δ 8.22 (d, J = 8.7 Hz, 2H), 7.56
(d, J = 8.7 Hz, 2H), 5.35 (d, J = 5.0 Hz, 1H), 4.56 (s, 2H), 3.72 (ddd, J = 16.5, 8.2, 4.3 Hz, 1H),
2.39 (dt, J = 12.9, 6.5 Hz, 1H), 2.22 – 2.07 (m, 1H), 2.03 – 0.88 (m, 32H), 0.85 (dd, J = 6.6, 1.8
Hz, 6H), 0.65 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 147.5, 144.5, 139.1, 128.1, 123.9, 123.2,
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61.3, 56.6, 56.0, 49.9, 48.3, 42.2, 39.6, 39.5, 37.8, 36.7, 36.4, 36.1, 35.7, 31.75, 31.7, 28.2, 27.9,
26.8, 24.2, 23.8, 22.8, 22.5, 20.9, 19.2, 18.7, 11.8. IR (KBr): 2935, 2136, 1540, 1518, 1364, 1261,
1165, 914, 857, 802, 738, 668, 609 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C34H51N5O4S
626.3735, found 626.3710.
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Methyl 2ꢀ(4ꢀ((azidosulfonyl)(benzo[d][1,3]dioxolꢀ5ꢀylmethyl)amino)butanamido)ꢀ3ꢀphenyl
propanoate (4c). A mixture of 4ꢀ((tertꢀbutoxycarbonyl)amino)butanoic acid (1.02 g, 5.0 mmol),
methyl phenylalaninate (0.81 g, 4.5 mmol), 1ꢀhydroxybenzotriazole (0.77 g, 4.3 mmol),
1ꢀethylꢀ3ꢀ(3ꢀdimethylaminopropyl)carbodiimide hydrochloride (0.99 g, 4.3 mmol) and
o
triethylamine (0.96 g, 9.5 mmol) in DMF (10 mL) was stirred at 0 C for 12 h. Then the reaction
mixture was washed by 10 % citric acid (15 mL x 3), 4 % NaHCO3 (15 mL x 3) and brine (15 mL
x 1). The obtained organic layer was dried over Na2SO4 and concentrated under reduced pressure
to afford the crude product. The crude residue was crystallized with hexane to afford methyl
(4ꢀ((tertꢀbutoxycarbonyl)amino)butanoyl)phenylalaninate. Yield 1.13g, 73%. 1H NMR (400 MHz,
CDCl3) δ 7.32 – 7.25 (m, 3H), 7.15 (d, J = 7.0 Hz, 2H), 6.55 (d, J = 5.7 Hz, 1H), 4.86 (d, J = 6.5
Hz, 1H), 4.79 (d, J = 4.9 Hz, 1H), 3.73 (s, 3H), 3.18 (dd, J = 13.9, 5.7 Hz, 2H), 3.07 (dd, J = 13.8,
6.8 Hz, 2H), 2.24 – 2.17 (m, 2H), 1.80 – 1.73 (m, 2H), 1.45 (s, 9H). To a solution of methyl
(4ꢀ((tertꢀbutoxycarbonyl)amino)butanoyl)phenylalaninate (364 mg, 1.0 mmol) in DCM (2 mL)
was added EtOAc (2 mL) containing 4 M HCl, and then the reaction mixture was stirred at room
temperature for 15 min. Upon completion, the solvent was evaporated to dryness. Addition of
Et2O (10 mL) and concentration under reduced pressure three times to remove the remained HCl.
The residue was dissolved in MeCN (0.5 mL) and then the product was precipitated by the
addition of Et2O (3 mL). The precipitant was dried in vacuo to afford methyl
(4ꢀaminobutanoyl)phenylalaninate hydrochloride (quant), which was used directly for next step.
To an oven dried round bottom flask (100 mL), benzo[d][1,3]dioxoleꢀ5ꢀcarbaldehyde (0.450 g, 3.0
mmol), methyl (4ꢀaminobutanoyl)phenylalaninate hydrochloride (1.350 g, 4.5 mmol),
triethylamine (0.606 g, 6.0 mmol), Na2SO4 (1.28 g, 9.0 mmol) , DCM (20 mL) and acetonitrile (20
mL) were added. The reaction mixture was stirred for 24 h, and then concentrated under reduced
pressure. MeOH (40 mL) and NaBH4 (0.228 g) was added to the concentrate and the mixture
continued stirring for additional 2 h. Water (30 mL) was added and the aqueous solution was
extracted with EtOAc (3 x 30 mL). The combined organic layer was dried with Na2SO4, filtered
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and concentrated under reduced pressure. The crude product was purified by short pad of silica gel
column using Petroleum Ether (PE) and Ethyl Acetate (EA) as eluent to afford methyl
2ꢀ(4ꢀ((benzo[d][1,3]dioxolꢀ5ꢀylmethyl)amino)butanamido)ꢀ3ꢀphenylpropanoate (0.836 g, 70%),
colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.24 – 7.14 (m, 3H), 7.06 (d, J = 7.0 Hz, 2H), 6.91
(d, J = 7.2 Hz, 1H), 6.75 (s, 1H), 6.71 – 6.63 (m, 2H), 5.82 (s, 2H), 4.83 (dd, J = 13.4, 6.5 Hz, 1H),
3.63 (s, 3H), 3.55 (s, 2H), 3.03 (ddd, J = 41.8, 13.9, 6.2 Hz, 2H), 2.52 (t, J = 5.6 Hz, 2H), 2.21 (t, J
= 6.4 Hz, 2H), 1.71 (dd, J = 13.5, 6.7 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 172.7, 172.2, 147.6,
146.4, 136.3, 134.4, 129.2, 128.4, 126.9, 121.1, 108.6, 108.0, 100.8, 53.4, 53.1, 52.1, 48.1, 37.8,
34.2, 25.5. The synthesis of compound 4c from methyl 2ꢀ(4ꢀ((benzo[d][1,3]dioxolꢀ5ꢀylmethyl)
amino)butanamido)ꢀ3ꢀphenylpropanoate was according to the general procedure for the synthesis
of sulfamoyl azides 1 and 4. Column chromatography (PE/EA 5/1) afforded 4c as a colorless oil
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(624 mg, 62%). TLC: Rf = 0.65 (PE/EA = 1/1). H NMR (400 MHz, CDCl3) δ 7.32 – 7.18 (m,
3H), 7.13 – 7.01 (m, 2H), 6.86 (d, J = 1.2 Hz, 1H), 6.83 – 6.71 (m, 2H), 5.96 (d, J = 5.0 Hz, 1H),
5.95 (s, 2H), 4.84 (dt, J = 7.7, 6.0 Hz, 1H), 4.34 (s, 2H), 3.72 (s, 3H), 3.22 (t, J = 7.2 Hz, 2H), 3.13
(dd, J = 13.9, 5.8 Hz, 1H), 3.05 (dd, J = 13.9, 6.2 Hz, 1H), 2.14 (td, J = 7.1, 3.1 Hz, 2H), 1.90 –
1.79 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 171.9, 171.1, 148.1, 147.8, 135.7, 129.1, 128.5,
128.0, 127.1, 122.4, 109.0, 108.3, 101.2, 53.0, 52.3, 52.26, 47.4, 37.7, 32.5, 22.8. IR (neat): 2128,
1746, 1661, 1540, 1505, 1446, 1380, 1246, 1165, 1102, 1039, 927, 810, 747, 668, 592 cmꢀ1;
HRMS (ESI) ([MꢀH]ꢀ) Calcd. for C22H25N5O7S 502.1402, found 502.1399.
Methyl
2ꢀ(4ꢀ((azidosulfonyl)(benzo[d][1,3]dioxolꢀ5ꢀylmethyl)amino)butanamido)ꢀ4ꢀ
(4d). The synthesis of compound 4d from
(methylthio)butanoate
4ꢀ((tertꢀbutoxycarbonyl)amino)butanoic acid and methyl methioninate was according to the
procedure for the synthesis of 4c. Methyl (4ꢀ((tertꢀbutoxycarbonyl)amino)butanoyl)methioninate
was obtained in 70% yield. 1H NMR (400 MHz, CDCl3) δ 6.95 (s, 1H), 4.86 (s, 1H), 4.68 (dd, J
= 7.1, 5.3 Hz, 1H), 3.75 (d, J = 6.7 Hz, 3H), 3.33 – 3.09 (m, 2H), 2.54 (t, J = 6.7 Hz, 2H), 2.28 (dd,
J = 11.4, 6.8 Hz, 2H), 2.22 – 2.12 (m, 1H), 2.10 (d, J = 6.3 Hz, 3H), 2.05 – 1.98 (m, 1H), 1.81 (dd,
J = 13.1, 6.5 Hz, 2H), 1.44 (d, J = 6.0 Hz, 9H). Methyl 2ꢀ(4ꢀ((benzo[d][1,3]
dioxolꢀ5ꢀylmethyl)amino)butanamido)ꢀ4ꢀ(methylthio)butanoate was obtained in 65% yield,
colorless oil. 1H NMR (400 MHz, CDCl3) δ 6.93 – 6.70 (m, 4H), 5.93 (ddd, J = 4.4, 2.5, 0.8 Hz,
2H), 4.70 (d, J = 4.4 Hz, 1H), 3.78 – 3.65 (m, 5H), 2.67 (d, J = 4.5 Hz, 2H), 2.56 – 2.43 (m, 2H),
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2.34 (d, J = 6.7 Hz, 2H), 2.14 (dd, J = 11.6, 6.4 Hz, 1H), 2.08 (ddd, J = 4.2, 2.4, 0.8 Hz, 3H), 1.95
(dd, J = 12.5, 6.4 Hz, 1H), 1.83 (d, J = 6.3 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 172.8, 172.6,
147.7, 146.5, 134.3, 121.1, 108.6, 108.0, 100.9, 53.6, 52.4, 51.4, 48.2, 34.4, 31.7, 30.1, 25.5, 15.5.
Column chromatography (PE/EA 5/1) afforded 4d as a colorless oil (536 mg, 55%). Rf = 0.65
(PE/EA = 1/1). 1H NMR (400 MHz, CDCl3) δ 6.86 (d, J = 1.2 Hz, 1H), 6.81 – 6.74 (m, 2H), 6.24
(d, J = 7.8 Hz, 1H), 5.96 (s, 2H), 4.67 (td, J = 7.6, 5.1 Hz, 1H), 4.35 (s, 2H), 3.73 (s, 3H), 3.26 (t, J
= 7.3 Hz, 2H), 2.48 (t, J = 6.9 Hz, 2H), 2.21 (t, J = 7.0 Hz, 2H), 2.17 – 2.09 (m, 1H), 2.07 (s, 3H),
2.00 – 1.91 (m, 1H), 1.90 – 1.81 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 172.3, 171.5, 148.1,
147.8, 128.0, 122.4, 109.0, 108.3, 101.3, 52.5, 52.3, 51.5, 47.5, 32.5, 31.4, 29.9, 22.7, 15.4. IR
(neat): 2921, 2128, 1744, 1656, 1533, 1504, 1445, 1379, 1246, 1165, 1099, 1039, 928, 811, 771,
668, 602 cmꢀ1; HRMS (ESI) ([MꢀH]ꢀ) Calcd. for C18H25N5O7S2 486.1122, found 486.1120.
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General procedure for rearrangement. A tube was capped with a teflon screw cap, evacuated,
and backfilled with nitrogen. The screw cap was replaced with a rubber septum, and sulfamoyl
azide (0.2 mmol) and dioxane (2.0 mL) were added via syringe. The tube was purged with
nitrogen for 2 min, and then the septum was replaced with the teflon screw cap. Then the tube was
sealed and stirred under the indicated conditions. After cooling to room temperature, the reaction
mixture was concentrated under reduced pressure. The residue was then purified by flash column
chromatography using SiO2 (hexane/ethyl acetate) to afford the desired products.
1ꢀMethoxyꢀ4ꢀphenethylbenzene (2a). Column chromatography (PE/EA 50/1) afforded 2a as a
o
1
white solid (36.0 mg, 85%). mp 59.1ꢀ60.2 C. TLC: Rf = 0.65 (PE/EA = 20/1). H NMR (400
MHz, CDCl3) δ 7.32 – 7.27 (m, 1H), 7.24 – 7.17 (m, 1H), 7.14 – 7.08 (m, 1H), 6.87 – 6.81 (m,
1H), 3.80 (s, 2H), 2.97 – 2.80 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 157.8, 141.8, 133.9, 129.3,
128.5, 128.3, 125.8, 113.7, 55.2, 38.2, 37.0. IR (KBr): 1540, 1151, 1454, 1246, 1037, 821, 749,
698, 668 cmꢀ1; HRMS (APCI) ([MꢀH]ꢀ) Calcd. for C15H16O 211.1128, found 211.1124. The
analytical data matched literature values.19
1,2ꢀDiphenylethane (2b). Column chromatography (PE/EA 50/1) afforded 2b as a white solid
(33.5 mg, 92%). mp 51.7ꢀ53.2 oC. TLC: Rf = 0.90 (PE/EA = 10/1). 1H NMR (400 MHz, CDCl3) δ
7.35 – 7.28 (m, 4H), 7.26 – 7.18 (m, 5H), 2.95 (s, 4H). 13C NMR (101 MHz, CDCl3) δ 141.8,
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128.4, 128.3, 125.9, 37.9. IR (KBr): 1541, 1275, 1261, 1030, 802, 750, 668 cmꢀ1; HRMS (APCI)
([MꢀH]ꢀ) Calcd. for C14H14 181.1023, found 181.1033.The analytical data matched literature
values.19
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1,2ꢀBis(4ꢀmethoxyphenyl)ethane (2c). Column chromatography (PE/EA 50/1) afforded 2c as a
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white solid (39.2 mg, 81%). mp 123.1ꢀ126.2 C. TLC: Rf = 0.50 (PE/EA = 50/1). H NMR (400
MHz, CDCl3) δ 7.14 – 7.04 (m, 4H), 6.88 – 6.79 (m, 4H), 3.79 (s, 6H), 2.83 (s, 4H). 13C NMR
(101 MHz, CDCl3) δ 157.8, 133.9, 129.3, 113.7, 55.2, 37.3. IR (KBr): 1540, 1262, 1246, 1030,
832, 748, 668 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C16H18O2 243.1380, found 243.1388. The
analytical data matched literature values.20
2ꢀ(4ꢀMethoxyphenethyl)naphthalene (2d). Column chromatography (PE/EA 50/1) afforded 2d
as a white solid (38.8 mg, 74%). mp 80.5ꢀ83.6 oC. TLC: Rf = 0.75 (PE/EA = 20/1). 1H NMR (400
MHz, CDCl3) δ 8.12 (d, J = 8.3 Hz, 1H), 7.90 (d, J = 7.7 Hz, 1H), 7.75 (d, J = 8.2 Hz, 1H), 7.63 –
7.46 (m, 2H), 7.46 – 7.37 (m, 1H), 7.31 (d, J = 6.9 Hz, 1H), 7.18 (d, J = 8.5 Hz, 2H), 6.88 (d, J =
8.5 Hz, 2H), 3.83 (s, 3H), 3.37 (dd, J = 9.5, 6.8 Hz, 2H), 3.03 (dd, J = 9.6, 6.8 Hz, 2H). 13C NMR
(101 MHz, CDCl3) δ 157.9, 137.8, 134.1, 133.9, 131.8, 129.3, 128.8, 126.7, 126.0, 125.8, 125.5,
125.4, 123.6, 113.8, 55.3, 36.2, 35.4. IR (KBr): 1540, 1511, 1245, 1177, 1105, 1036, 797, 749,
668 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C19H18O 263.1431, found 263.1433.
1ꢀFluoroꢀ4ꢀ(4ꢀmethoxyphenethyl)benzene (2e). Column chromatography (PE/EA 80/1) afforded
2e as a white solid (38.2 mg, 83%).. mp 66.1ꢀ67.6 C. TLC: Rf = 0.70 (PE/EA = 50/1). 1H NMR
o
(400 MHz, CDCl3) δ 7.14 – 7.04 (m, 4H), 7.00 – 6.92 (m, 2H), 6.86 – 6.80 (m, 2H), 3.80 (s, 3H),
2.92 – 2.78 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 161.31 (d, J = 243.3 Hz), 157.9, 137.39 (d, J
= 3.2 Hz), 133.5, 129.84 (d, J = 7.8 Hz), 129.4, 114.99 (d, J = 21.0 Hz), 113.8, 55.3, 37.3, 37.10
(d, J = 0.6 Hz).19F NMR (376 MHz, CDCl3) δ ꢀ117.70.IR (neat): 1541, 1510, 1261, 1104, 1037,
806, 748, 668 cmꢀ1; HRMS (APCI) ([MꢀH]ꢀ) Calcd. for C15H15FO 229.1034, found 229.1033. The
analytical data matched literature values.21
1ꢀChloroꢀ4ꢀ(4ꢀmethoxyphenethyl)benzene (2f). Column chromatography (PE/EA 100/1)
afforded 2f as a white solid (44.0 mg, 89%). mp 68.3ꢀ70.6 oC. TLC: Rf = 0.70 (PE/EA = 50/1). 1H
NMR (400 MHz, CDCl3) δ 7.26 – 7.21 (m, 2H), 7.11 – 7.04 (m, 4H), 6.86 – 6.80 (m, 2H), 3.80 (s,
3H), 2.94 – 2.77 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 157.9, 140.2, 133.3, 131.6, 129.8, 129.3,
128.3, 113.8, 55.2, 37.4, 36.81. IR (KBr): 1568, 1540, 1261, 1104, 750 cmꢀ1; HRMS (APCI)
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([M+H]+) Calcd. for C15H15ClO 247.0884, found 247.0886. The analytical data matched literature
values.21
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1ꢀBromoꢀ4ꢀ(4ꢀmethoxyphenethyl)benzene (2g). Column chromatography (PE/EA 100/1)
afforded 2g as a white solid (55.3 mg, 95%). mp 74.5ꢀ78.9 oC .TLC: Rf = 0.70 (PE/EA = 50/1). 1H
NMR (400 MHz, CDCl3) δ 7.46 – 7.32 (m, 2H), 7.13 – 6.99 (m, 4H), 6.88 – 6.73 (m, 2H), 3.80 (s,
3H), 2.85 (s, 4H). 13C NMR (101 MHz, CDCl3) δ 157.9, 140.7, 133.3, 131.3, 130.3, 129.3, 119.6,
113.8, 55.2, 37.5, 36.7. IR (KBr): 1568, 1540, 1262, 1104, 1034, 827, 749 cmꢀ1; HRMS (APCI)
([M+H]+) Calcd. for C15H15BrO 291.0379, found 291.0384. The analytical data matched literature
values.22
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4ꢀ(4ꢀMethoxyphenethyl)benzonitrile (2h). Column chromatography (PE/EA 50/1) afforded 2h
as a white solid (39.3 mg, 83%). mp 98.6ꢀ100.1 oC TLC: Rf = 0.70 (PE/EA = 20/1). 1H NMR (400
MHz, CDCl3) δ 7.54 (d, J = 8.1 Hz, 2H), 7.22 (d, J = 8.1 Hz, 2H), 7.03 (d, J = 8.5 Hz, 2H), 6.82
(d, J = 8.5 Hz, 2H), 3.79 (s, 3H), 3.01 – 2.92 (m, 2H), 2.91 – 2.83 (m, 2H). 13C NMR (101 MHz,
CDCl3) δ 158.0, 147.3, 132.6, 132.0, 129.3, 129.3, 119.0, 113.8, 109.7, 55.2, 38.1, 36.3. IR (KBr):
2228, 1541, 1510, 1455, 1263, 1176, 1097, 1033, 832, 745, 668, 547 cmꢀ1; HRMS (APCI)
([M+H]+) Calcd. for C16H15NO 238.1227, found 238.1223. The analytical data matched literature
values.23
1ꢀMethoxyꢀ4ꢀ(4ꢀnitrophenethyl)benzene (2i). Column chromatography (PE/EA 20/1) afforded
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2i as a pale yellow solid (43.7 mg, 85%). mp 84.7ꢀ85.2 C. TLC: Rf = 0.45 (PE/EA = 10/1). H
NMR (400 MHz, CDCl3) δ 8.12 (d, J = 8.6 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 7.03 (d, J = 8.5 Hz,
2H), 6.82 (d, J = 8.5 Hz, 2H), 3.79 (s, 3H), 3.00 (t, J = 7.5 Hz, 2H), 2.90 (t, J = 7.5 Hz, 2H). 13C
NMR (101 MHz, CDCl3) δ 158.1, 149.5, 146.4, 132.5, 129.3, 123.5, 113.9, 55.2, 37.9, 36.3. IR
(KBr): 1599, 1540, 1510, 1346, 1275, 1261, 1243, 1177, 1106, 1031, 847, 801, 749, 723, 668
cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C15H15NO3 258.1125, found 258.1116. The analytical
data matched literature values.24
1ꢀ(4ꢀMethoxyphenethyl)ꢀ3,5ꢀbis(trifluoromethyl)benzene (2j). Column chromatography
o
(PE/EA 100/1) afforded 2j as a white solid (55.0 mg, 79%). mp 92.7ꢀ95.2 C. TLC: Rf = 0.70
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(PE/EA = 50/1). H NMR (400 MHz, CDCl3) δ 7.72 (s, 1H), 7.56 (s, 2H), 7.05 (d, J = 8.6 Hz,
2H), 6.84 (d, J = 8.6 Hz, 2H), 3.80 (s, 3H), 3.02 (dd, J = 9.1, 6.4 Hz, 2H), 2.90 (dd, J = 9.1, 6.4
Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 158.3, 144.0, 132.3, 131.45 (q, J = 33.0 Hz), 129.4,
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128.74 (d, J = 2.5 Hz), 123.43 (q, J = 272.6 Hz), 120.00 (dt, J = 7.8, 3.9 Hz), 113.99, 55.2, 37.8,
36.5. 19F NMR (376 MHz, CDCl3) δ ꢀ62.87. IR (KBr): 1541, 1514, 1381, 1277, 1261, 1174, 1130,
1037, 890, 806, 749, 705, 682, 668 cmꢀ1; HRMS (APCI) ([MꢀH]ꢀ) Calcd. for C17H14F6O 347.0876,
found 347.0890.
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Tertꢀbutyl(2ꢀ(4ꢀmethoxyphenethyl)phenyl)sulfane (2k). Column chromatography (PE/EA
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100/1) afforded 2k as a colorless oil. (45.0 mg, 75%). TLC: Rf = 0.75 (PE/EA = 50/1). H NMR
(400 MHz, CDCl3) δ 7.57 (d, J = 7.4 Hz, 1H), 7.31 – 7.24 (m, 2H), 7.20 – 7.12 (m, 3H), 6.87 –
6.81 (m, 2H), 3.80 (s, 3H), 3.25 – 3.10 (m, 2H), 2.87 – 2.68 (m, 2H), 1.31 (s, 9H). 13C NMR (101
MHz, CDCl3) δ 157.8, 147.3, 138.9, 134.3, 131.9, 129.6, 129.3, 128.9, 125.9, 113.7, 55.3, 47.0,
37.2, 37.0, 31.2. IR (neat): 1568, 1540, 1362, 1245, 1104, 1038, 805, 751, 668 cmꢀ1; HRMS
(APCI) ([M+H]+) Calcd. for C19H24OS 301.1621, found 301.1625.
1ꢀMethoxyꢀ4ꢀ(2ꢀphenylpropyl)benzene (2l). Column chromatography (PE/EA 100/1) afforded 2l
as a colorless oil. (38.9 mg, 86%). TLC: Rf = 0.80 (PE/EA = 50/1). 1H NMR (400 MHz, CDCl3) δ
7.33 – 7.26 (m, 2H), 7.23 – 7.15 (m, 3H), 7.00 (d, J = 8.6 Hz, 2H), 6.84 – 6.75 (m, 2H), 3.78 (s,
3H), 3.05 – 2.86 (m, 2H), 2.73 (dd, J = 13.3, 8.0 Hz, 1H), 1.25 (d, J = 6.8 Hz, 3H). 13C NMR
(101 MHz, CDCl3) δ 157.8, 147.0, 132.9, 130.0, 128.2, 127.1, 125.9, 113.5, 55.2, 44.1, 42.0,
21.1.IR (neat): 1541, 1510, 1454, 1261, 1104, 805, 748, 668 cmꢀ1; HRMS (APCI) ([MꢀH]ꢀ) Calcd.
for C16H18O 225.1285, found 225.1279. The analytical data matched literature values.23
2ꢀPhenethylpyridine (2m). Column chromatography (PE/EA 10/1) afforded 2m as a yellow oil.
(27.8 mg, 76%).. TLC: Rf = 0.30 (PE/EA = 10/1). 1H NMR (400 MHz, CDCl3) δ 8.57 (d, J = 4.3
Hz, 1H), 7.56 (td, J = 7.7, 1.8 Hz, 1H), 7.31 – 7.25 (m, 2H), 7.23 – 7.16 (m, 3H), 7.14 – 7.06 (m,
2H), 3.14 – 3.03 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 161.2, 149.3, 141.5, 136.2, 128.4, 128.3,
125.9, 122.9, 121.1, 40.2, 36.0. IR (neat): 1589, 1541, 1434, 1262, 1103, 802, 745, 668 cmꢀ1;
HRMS (APCI) ([M+H]+) Calcd. for C13H13N 184.1121, found 184.1117. The analytical data
matched literature values.25
2ꢀ(4ꢀNitrophenethyl)furan (2n). Column chromatography (PE/EA 30/1) afforded 2n as a white
o
solid. (41.2 mg, 95%). mp 91.0ꢀ92.6 C. TLC: Rf = 0.65 (PE/EA = 10/1). 1H NMR (400 MHz,
CDCl3) δ 8.13 (d, J = 8.7 Hz, 2H), 7.32 (d, J = 1.2 Hz, 1H), 7.29 (d, J = 8.7 Hz, 2H), 6.26 (dd, J =
3.0, 1.9 Hz, 1H), 5.94 (d, J = 3.1 Hz, 1H), 3.10 – 3.03 (m, 2H), 3.02 – 2.93 (m, 2H). 13C NMR
(101 MHz, CDCl3) δ 153.9, 148.9, 141.2, 129.2, 123.6, 110.2, 105.9, 34.3, 29.3. IR (KBr): 1541,
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1516, 1344, 1262, 1107, 802, 668 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C12H11NO3 218.0812,
found 218.0808. The analytical data matched literature values.24
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1,2ꢀDi(thiophenꢀ2ꢀyl)ethane (2o). Column chromatography (PE/EA 100/1) afforded 2o as a
o
white solid. (34.5 mg, 89%). mp 60.1ꢀ62.2 C. TLC: Rf = 0.75 (PE/EA = 50/1). 1H NMR (400
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MHz, CDCl3) δ 7.14 (dd, J = 5.1, 1.0 Hz, 2H), 6.93 (dd, J = 5.1, 3.4 Hz, 2H), 6.81 (d, J = 3.3 Hz,
2H), 3.21 (s, 4H). 13C NMR (101 MHz, CDCl3) δ 143.7, 126.7, 124.6, 123.3, 32.1. IR (KBr):
1540, 1434, 1262, 1104, 803, 668 cmꢀ1; HRMS (APCI) ([MꢀH]ꢀ) Calcd. for C10H10S2 193.0151,
found 193.0145. The analytical data matched literature values.20
1,2ꢀDi(furanꢀ2ꢀyl)ethane (2p). Column chromatography (PE/EA 100/1) afforded 2p as a
colorless oil. (25.3 mg, 78%). TLC: Rf = 0.60 (PE/EA = 50/1). 1H NMR (400 MHz, CDCl3) δ 7.35
– 7.28 (m, 2H), 6.28 (dd, J = 3.0, 1.9 Hz, 2H), 6.00 (d, J = 3.1 Hz, 2H), 2.98 (s, 4H). 13C NMR
(101 MHz, CDCl3) δ 154.9, 141.0, 110.1, 105.2, 26.7. IR (neat): 1541, 1261, 1104, 803, 748, 668
cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C10H10O2 163.0754, found 163.0744. The analytical
data matched literature values.26
(Cyclopentylmethyl)benzene (2q). Column chromatography (PE/EA 100/1) afforded 2q as a
colorless oil. (17.6 mg, 55%). TLC: Rf = 0.80 (PE/EA = 50/1). 1H NMR (400 MHz, CDCl3) δ 7.30
– 7.24 (m, 2H), 7.21 – 7.14 (m, 3H), 2.61 (d, J = 7.4 Hz, 2H), 2.09 (dt, J = 15.5, 7.7 Hz, 1H), 1.77
– 1.59 (m, 4H), 1.58 – 1.46 (m, 2H), 1.30 – 1.13 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 142.4,
128.8, 128.1, 125.5, 42.1, 42.0, 32.5, 24.9. IR (neat): 1541, 1262, 1104, 802, 748, 668 cmꢀ1;
HRMS (APCI) ([M+H]+) Calcd. for C12H16 161.1325, found 161.1326. The analytical data
matched literature values.27
1ꢀ(Cyclopentylmethyl)ꢀ4ꢀmethoxybenzene (2r). Column chromatography (PE/EA 100/1)
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afforded 2r as a colorless oil. (22.4 mg, 59%). TLC: Rf = 0.70 (PE/EA = 50/1). H NMR (400
MHz, CDCl3) δ 7.09 (d, J = 8.6 Hz, 2H), 6.82 (d, J = 8.6 Hz, 2H), 3.79 (s, 3H), 2.55 (d, J = 7.4
Hz, 2H), 2.05 (dt, J = 15.6, 7.9 Hz, 1H), 1.75 – 1.59 (m, 4H), 1.54 – 1.43 (m, 2H), 1.27 – 1.10 (m,
2H). 13C NMR (101 MHz, CDCl3) δ 157.6, 134.5, 129.6, 113.5, 55.2, 42.2, 41.2, 32.4, 24.9. IR
(neat): 1541, 1275, 1261, 1043, 803, 750, 668 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C13H18O
191.1431, found 191.1427. The analytical data matched literature values.27
1ꢀ(Cyclopentylmethyl)ꢀ4ꢀnitrobenzene (2s). Column chromatography (PE/EA 20/1) afforded 2s
as a colorless oil. (29.1 mg, 71%). TLC: Rf = 0.60 (PE/EA = 10/1). 1H NMR (400 MHz, CDCl3) δ
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8.13 (d, J = 8.7 Hz, 2H), 7.31 (d, J = 8.7 Hz, 2H), 2.71 (d, J = 7.5 Hz, 2H), 2.11 (dq, J = 15.7, 7.8
Hz, 1H), 1.75 – 1.60 (m, 4H), 1.59 – 1.47 (m, 2H), 1.28 – 1.13 (m, 2H). 13C NMR (101 MHz,
CDCl3) δ 150.3, 146.2, 129.5, 123.5, 41.9, 41.6, 32.4, 24.9. IR (neat): 1647, 1540, 1517, 1346,
1261, 1109, 857, 802, 749, 668 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C12H15NO2 206.1176,
found 206.1176. The analytical data matched literature values.27
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1ꢀMethoxyꢀ4ꢀ(3,3,3ꢀtrifluoropropyl)benzene (2t). Column chromatography (PE/EA 100/1)
afforded 2t as a colorless oil. (23.3 mg, 57%).. TLC: Rf = 0.70 (PE/EA = 50/1). 1H NMR (400
MHz, CDCl3) δ 7.11 (d, J = 8.6 Hz, 2H), 6.85 (d, J = 8.6 Hz, 2H), 3.80 (s, 3H), 2.86 – 2.77 (m,
2H), 2.43 – 2.26 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 158.4, 131.1, 129.2, 126.72 (q, J = 276.9
Hz), 114.1, 55.3, 36.61 – 34.96 (m), 27.33 (q, J = 2.9 Hz). 19F NMR (376 MHz, CDCl3) δ ꢀ66.64.
IR (KBr): 1540, 1261, 1104, 802, 749, 668 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C10H11F3O
205.0835, found 205.0827.
3ꢀ(3ꢀPhenylpropyl)ꢀ1ꢀtosylꢀ1Hꢀindole (2u). Column chromatography (PE/EA 20/1) afforded 2u
as a white solid (59.9 mg, 77%). mp 82.9ꢀ85.6 oC. TLC: Rf = 0.50 (PE/EA = 10/1). 1H NMR (400
MHz, CDCl3) δ 7.99 (d, J = 8.3 Hz, 1H), 7.74 (d, J = 8.3 Hz, 2H), 7.44 (d, J = 7.8 Hz, 1H), 7.33 –
7.27 (m, 4H), 7.24 – 7.15 (m, 6H), 2.68 (dd, J = 15.2, 7.8 Hz, 4H), 2.32 (s, 3H), 2.08 – 1.96 (m,
2H). 13C NMR (101 MHz, CDCl3) δ 144.6, 141.9, 135.4, 135.36, 131.1, 129.7, 128.4, 128.36,
126.7, 125.9, 124.6, 123.1, 122.9, 122.7, 119.5, 113.8, 35.4, 30.5, 24.4, 21.5. IR (KBr): 1541,
1447, 1372, 1263, 1173, 1119, 810, 745, 668 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for
C24H23NO2S 390.1522, found 390.1513.
Ethyl 3ꢀ(thiophenꢀ2ꢀyl)propanoate (2v). Column chromatography (PE/EA 100/1) afforded 2v as
a colorless oil (24.3 mg, 66%). TLC: Rf = 0.80 (PE/EA = 50/1). 1H NMR (400 MHz, CDCl3) δ
7.12 (d, J = 5.1 Hz, 1H), 6.94 – 6.89 (m, 1H), 6.82 (d, J = 2.6 Hz, 1H), 4.15 (q, J = 7.1 Hz, 2H),
3.17 (t, J = 7.6 Hz, 2H), 2.68 (t, J = 7.6 Hz, 2H), 1.25 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz,
CDCl3) δ 172.3, 143.1, 126.8, 124.6, 123.4, 60.5, 36.2, 25.2, 14.2. IR (neat): 1568, 1540, 1261,
1104, 803, 748, 668 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C9H12O2S 185.0631, found
185.0637. The analytical data matched literature values.28
Ethyl 2ꢀ(4ꢀmethoxybenzyl)ꢀ4ꢀmethylpentanoate (2w). Column chromatography (PE/EA 100/1)
afforded 2w as a colorless oil. (32.7 mg, 62%). TLC: Rf = 0.65 (PE/EA = 50/1). 1H NMR (400
MHz, CDCl3) δ 7.07 (d, J = 8.6 Hz, 2H), 6.80 (d, J = 8.6 Hz, 2H), 4.04 (qd, J = 7.1, 1.0 Hz, 2H),
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3.78 (s, 3H), 2.88 – 2.79 (m, 1H), 2.73 – 2.62 (m, 2H), 1.71 – 1.52 (m, 2H), 1.32 – 1.21 (m, 1H),
1.14 (t, J = 7.1 Hz, 3H), 0.88 (dd, J = 6.5, 1.7 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 175.9,
158.1, 131.5, 129.8, 113.7, 60.0, 55.2, 46.0, 41.4, 38.2, 26.2, 23.1, 21.9, 14.2. IR (neat): 1731,
1540, 1513, 1456, 1247, 1177, 1157, 1105, 1037, 806, 747, 668 cmꢀ1; HRMS (APCI) ([M+H]+)
Calcd. for C16H24O3 265.1798, found 265.1793.
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Ethyl 2ꢀbenzylꢀ3ꢀ(4ꢀmethoxyphenyl)propanoate (2x)29. Column chromatography (PE/EA 100/1)
afforded 2x as a colorless oil. (47.7 mg, 80%).. TLC: Rf = 0.65 (PE/EA = 50/1). 1H NMR (400
MHz, CDCl3) δ 7.30 – 7.24 (m, 2H), 7.20 (d, J = 7.2 Hz, 1H), 7.18 – 7.14 (m, 2H), 7.11 – 7.04 (m,
2H), 6.85 – 6.78 (m, 2H), 3.96 (q, J = 7.1 Hz, 2H), 3.78 (s, 3H), 3.00 – 2.87 (m, 3H), 2.84 – 2.70
(m, 2H), 1.02 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 174.9, 158.1, 139.2, 131.2,
129.9, 128.9, 128.3, 126.3, 113.8, 60.1, 55.2, 49.8, 38.2, 37.4, 14.03.IR (neat): 1731, 1541, 1514,
1454, 1248, 1176, 1105, 1036, 805, 744, 668 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C19H22O3
299.1642, found 299.1641.
1ꢀMethoxyꢀ4ꢀneopentylbenzene (2y). Column chromatography (PE/EA 100/1) afforded 2y as a
colorless oil. (20.6 mg, 58%). TLC: Rf = 0.75 (PE/EA = 50/1). 1H NMR (400 MHz, CDCl3) δ 7.04
(d, J = 8.5 Hz, 2H), 6.82 (d, J = 8.5 Hz, 2H), 3.80 (s, 3H), 2.44 (s, 2H), 0.89 (s, 9H). 13C NMR
(101 MHz, CDCl3) δ 157.8, 131.9, 131.3, 113.0, 55.2, 49.3, 31.7, 29.3. IR (neat): 1541, 1275.
1261, 1103, 803, 750, 668 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C12H18O 179.1431, found
179.1424. The analytical data matched literature values.30
1ꢀ(2ꢀCyclopropylethyl)ꢀ4ꢀmethoxybenzene (2z). Column chromatography (PE/EA 100/1)
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afforded 2z as a colorless oil. (19.4 mg, 55%). TLC: Rf = 0.70 (PE/EA = 50/1). H NMR (400
MHz, CDCl3) δ 7.12 (d, J = 8.6 Hz, 2H), 6.83 (d, J = 8.6 Hz, 2H), 3.79 (s, 3H), 2.72 – 2.61 (m,
2H), 1.49 (dd, J = 15.2, 7.1 Hz, 2H), 0.78 – 0.63 (m, 1H), 0.51 – 0.35 (m, 2H), 0.07 – 0.02 (m,
2H). 13C NMR (101 MHz, CDCl3) δ 157.6, 134.8, 129.3, 113.6, 55.2, 36.9, 35.0, 10.7, 4.5. IR
(neat): 1540, 1515, 1261, 1104, 804, 668 cmꢀ1; HRMS (APCI) ([M+H]+) Calcd. for C12H16O
177.1274, found 177.1269. The analytical data matched literature values.31
1ꢀ(Benzyloxy)ꢀ2,2,6,6ꢀtetramethylpiperidine (2b′). A tube was capped with a teflon screw cap,
evacuated, and backfilled with nitrogen. The screw cap was replaced with a rubber septum, and
sulfamoyl azide 1b (60.4 mg, 0.2 mmol), TEMPO (0.04 mmol to 0.6 mmol) and dry dioxane (2.0
mL) were added via syringe. The tube was purged with nitrogen for 2 min, and then the septum
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was replaced with the teflon screw cap. Then the tube was sealed and stirred under the indicated
conditions. After cooling to room temperature, the reaction mixture was concentrated in vacuum.
The residue was then purified by flash column chromatography using SiO2 (hexane/ethyl acetate)
to afford the products 2b and 2b′. Column chromatography (PE/EA 100/1) afforded 2b′ as a
colorless oil (18.8 mg, 38%). TLC: Rf = 0.55 (PE/EA = 50/1).1H NMR (400 MHz, CDCl3) δ 7.40
– 7.32 (m, 5H), 7.31 – 7.27 (m, 1H), 4.84 (s, 2H), 1.62 – 1.44 (m, 5H), 1.40 – 1.33 (m, 1H), 1.22
(d, J = 40.9 Hz, 12H). 13C NMR (101 MHz, CDCl3) δ 138.3, 128.2, 127.4, 127.3, 78.7, 60.0, 39.7,
33.1, 20.3, 17.1. HRMS (ESI) ([M+H]+) Calcd. for C16H25NO 248.2009, found 248.2005.
(8S,9S,10R,13R,14S,17R)ꢀ3ꢀ(4ꢀBromobenzyl)ꢀ17ꢀ((S,E)ꢀ4ꢀethylꢀ3,5ꢀdimethylhexꢀ2ꢀenꢀ1ꢀyl)ꢀ10
,13ꢀdimethylꢀ2,3,4,7,8,9,10,11,12,13,14,15,16,17ꢀtetradecahydroꢀ1Hꢀcyclopenta[a]phenanthre
ne (5a). Column chromatography (PE/EA 100/1) afforded 5a as a white solid. (79.2 mg, 70%, d/r
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= 2/1 (by mix H NMR)). mp 95.8ꢀ97.6 oC. TLC: Rf = 0.85 (PE/EA = 50/1). 1H NMR (400 MHz,
CDCl3) δ 7.37 (dd, J = 8.7, 2.1 Hz, 2H), 7.01 (dd, J = 8.3, 3.3 Hz, 2H), 5.23(5.27) (d, J = 3.9 Hz,
1H), 5.15 (dd, J = 15.2, 8.5 Hz, 1H), 5.01 (dd, J = 15.1, 8.7 Hz, 1H), 2.59 – 2.38 (m, 2H), 2.11 –
1.89 (m, 5H), 1.81 (dd, J = 13.1, 3.3 Hz, 1H), 1.75 – 1.37 (m, 10H), 1.32 – 0.77 (m, 25H),
0.69(0.70) (s, 3H). 13C NMR (101 MHz, CDCl3) δ 142.9, 139.9, 138.4, 131.1, 130.8, 129.2, 119.7,
119.4, 56.9, 55.9, 51.2, 50.5, 43.2, 42.2, 41.2, 40.5, 39.7, 39.4, 39.3, 37.2, 31.9, 28.9, 28.8, 25.4,
24.3, 21.2, 21.1, 20.9, 19.5, 19.0, 12.2, 12.1. IR (KBr): 1540, 1454, 1261, 1104, 800, 749, 668
cmꢀ1; HRMS (APCI) ([MꢀH]ꢀ) Calcd. for C36H53Br 563.3258, found 563.3262.
(8S,9S,10R,13R,14S,17R)ꢀ10,13ꢀDimethylꢀ17ꢀ((R)ꢀ6ꢀmethylheptanꢀ2ꢀyl)ꢀ3ꢀ(4ꢀnitrobenzyl)ꢀ2,3,
4,7,8,9,10,11,12,13,14,15,16,17ꢀtetradecahydroꢀ1Hꢀcyclopenta[a]phenanthrene (5b). Column
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chromatography (PE/EA 50/1) afforded 5b as a white solid. (79.9 mg, 79%, d/r = 2/1 (by mix H
NMR)). mp 119.4 oC ꢀ decomposition. TLC: Rf = 0.80 (PE/EA = 20/1). 1H NMR (400 MHz,
CDCl3) δ 8.13 (d, J = 8.6 Hz, 2H), 7.34 – 7.27 (m, 2H), 5.23(5.28) (d, J = 4.8 Hz, 1H), 2.76 – 2.55
(m, 2H), 2.51 – 2.41 (m, 1H), 2.11 – 1.72 (m, 6H), 1.68 – 1.60 (m, 1H), 1.56 – 1.22 (m, 11H),
1.20 – 0.83 (m, 22H), 0.67(0.69) (s, 3H). 13C NMR (101 MHz, CDCl3) δ 150.2, 149.0, 146.4,
146.2, 142.4, 139.9, 129.9, 129.8, 123.5, 123.4, 122.2, 120.1, 56.9, 56.8, 56.2, 56.2, 50.7, 50.4,
43.6, 42.4, 42.3, 41.2, 39.8, 39.5, 39.3, 39.28, 37.5, 37.4, 37.1, 36.6, 36.22, 36.19, 35.9, 35.82,
35.78, 34.0, 33.9, 32.0, 31.9, 28.8, 28.3, 28.2, 28.0, 25.9, 24.3, 24.27, 23.9, 23.8, 22.8, 22.6, 20.9,
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20.8, 19.5, 18.7, 18.72, 11.9. IR (KBr): 2933, 1540, 1517, 1345, 1262, 1108, 804, 746, 668 cmꢀ1;
HRMS (APCI) ([M+H]+) Calcd. for C34H51NO2 506.3993, found 506.3985.
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Methyl (5ꢀ(benzo[d][1,3]dioxolꢀ5ꢀyl)pentanoyl)phenylalaninate (5c). Column chromatography
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(PE/EA 3/1) afforded 5c as a white solid. (47.5 mg, 62%). mp 82.3ꢀ84.6 C. TLC: Rf = 0.15
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(PE/EA = 3/1). 1H NMR (400 MHz, CDCl3) δ 7.30 – 7.22 (m, 3H), 7.07 (d, J = 6.4 Hz, 2H), 6.71
(d, J = 7.9 Hz, 1H), 6.64 (s, 1H), 6.59 (d, J = 7.8 Hz, 1H), 5.91 (s, 2H), 5.85 (d, J = 7.8 Hz, 1H),
4.89 (dd, J = 13.6, 5.8 Hz, 1H), 3.73 (s, 3H), 3.11 (qd, J = 13.8, 5.8 Hz, 2H), 2.52 (t, J = 7.2 Hz,
2H), 2.18 (t, J = 7.1 Hz, 2H), 1.74 – 1.47 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 172.3, 172.1,
147.5, 145.5, 135.9, 135.8, 129.2, 128.5, 127.1, 121.1, 108.8, 108.1, 100.7, 52.9, 52.3, 37.9, 36.3,
35.3, 31.1, 25.0. IR (neat): 1748, 1661, 1540, 1506, 1489, 1441, 1245, 1103, 1038, 805, 746, 668
cmꢀ1; HRMS (ESI) ([MꢀH]ꢀ) Calcd. for C22H25NO5 382.1660, found 382.1658. The analytical data
matched literature values.32
Methyl (5ꢀ(benzo[d][1,3]dioxolꢀ5ꢀyl)pentanoyl)methioninate (5d). Column chromatography
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(PE/EA 3/1) afforded 5d as a white solid. (36.7 mg, 50%). mp 64.9ꢀ73.6 C. TLC: Rf = 0.20
(PE/EA = 3/1). 1H NMR (400 MHz, CDCl3) δ 6.70 (d, J = 7.9 Hz, 1H), 6.65 (s, 1H), 6.60 (d, J =
7.8 Hz, 1H), 6.15 (d, J = 7.6 Hz, 1H), 5.91 (d, J = 5.5 Hz, 2H), 4.71 (dt, J = 12.7, 6.4 Hz, 1H),
3.75 (d, J = 2.5 Hz, 3H), 2.60 – 2.43 (m, 4H), 2.23 (t, J = 7.2 Hz, 2H), 2.18 – 2.11 (m, 1H), 2.07
(s, 3H), 2.02 – 1.91 (m, 1H), 1.71 – 1.55 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 172.6, 172.5,
147.5, 145.5, 135.9, 121.0, 108.8, 108.1, 100.7, 52.5, 51.4, 36.3, 35.3, 31.7, 31.2, 30.0, 25.0, 15.5.
IR (neat): 1747, 1661, 1563, 1540, 1489, 1434, 1245, 1103, 1038, 804, 668 cmꢀ1; HRMS (ESI)
([MꢀH]ꢀ) Calcd. for C18H25NO5S 366.1380, found 366.1380. The analytical data matched literature
values.32
Supporting Information
Experimental details and NMR spectra. This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
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