A Metal-Free Protocol for Aminofunctionalization of Olefins Using TsNBr2

Article abstract of DOI:10.1021/acs.joc.6b00785

N,N-Dibromo-p-toluene sulfonamide (TsNBr₂) has been found to be an effective reagent for various aminofunctionalization reactions. This reagent behaves both as an electrophilic bromine source as well as amine to react with olefins under different conditions to yield aminoether, imidazoline, diamine and amino bromine. The reaction proceeds rapidly under mild conditions with high regioselectivity. Olefins react with TsNBr₂ in moist THF to form δ-amino ether at room temperature. Treatment of TsNBr₂ with olefin in MeCN at room temperature produced imidazoline in high yield. Further modification of the reaction condition resulted in the development of a one-step procedure for the synthesis of N-acetyl,N′-tosyl diamine derivatives directly from olefin. When the olefin was treated with 2.4 mol equiv of TsNBr₂ in the presence of K₂CO₃, N,N′-ditosyl diamine derivative was obtained in moderate yield. Instantaneous formation of aminobromine was observed when an olefin was treated with the reagent in dry CH₂Cl₂ at room temperature.

Full text of DOI:10.1021/acs.joc.6b00785

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Article
A metal free protocol for aminofunctionalization of olefins using TsNBr2
Kamal Krishna Rajbongshi, Indranirekha Saikia, Subhasish
Roy, Loukrakpam Dineshwori Chanu, and Prodeep Phukan
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00785 • Publication Date (Web): 06 Jun 2016
Downloaded from http://pubs.acs.org on June 7, 2016
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A metal free protocol for aminofunctionalization of olefins using TsNBr2
.
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Kamal Krishna Rajbongshi, Indranirekha Saikia, Loukrakpam Dineshwori Chanu, Subhasish
Roy and Prodeep Phukan*
9
Department of Chemistry, Gauhati University, Guwahati, 781014, Assam, India
Eꢀmail: pphukan@yahoo.com
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Abstract:
NHTs
R1
R
Br
CH2Cl2
0-25 °C, N2
R1
R
O
TsNBr2
NTs
CH3CN
0-25° C
THF
NHTs
R
R1
Br
0-25° C
R1
N
R
25 oC
MeCN-H2O
R
NHAc
R1
NHTs
N,NꢀDibromoꢀpꢀtoluene sulfonamide (TsNBr2) has been found to be an effective
reagent for various aminofunctionalization reactions. This reagent behaves both as an
electrophilic bromine source as well as amine to reacts with olefins under different conditions
to yield aminoether, imidazoline, diamine and amino bromine. The reaction proceeds rapidly
under mild conditions with high regioselectivity. Olefins react with TsNBr2 in moist THF to
form δꢀamino ether at room temperature. Treatment of TsNBr2 with olefin in MeCN at room
temperature produced imidazoline in high yield. Further modification of the reaction
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condition resulted in the development of a oneꢀstep procedure for the synthesis of Nꢀ
acetyl,N'ꢀtosyl diamine derivatives directly from olefin. When the olefin was treated with 2.4
molar equivalent of TsNBr2 in presence of K2CO3, N,N'ꢀditosyl diamine derivative was
obtained in moderate yield. Instantaneous formation of aminobromine was observed when an
olefin was treated with the reagent in dry CH2Cl2 at room temperature.
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Key words: Olefin; TsNBr2; Aminoether; Imidazoline; Diamine; Bromoamine.
INTRODUCTION
Carbonꢀnitrogen bond formation reaction is an important tool in organic chemistry for the
construction of nitrogenꢀcontaining natural products, materials and many bioactive molecules
with high medicinal value. Among them, haloamines, diamines, amidines and imidazolines
are of great interest as they are the structural unit found in different natural products and
alkaloids and also responsible for the biological activity of various organic compounds.1
O
N
CO2H
OR
NH
NH
O
O
RO
NHR2
NHR1
O
NH2
NHAc
N
H
4, 5ꢀDihydroꢀ6'ꢀdeoxybromotopsentin (I)
2ꢀAminoꢀβꢀglycosylamines (II)
Oseltamivir (III)
Figure 1: Some biologically active amino compounds
For example, 4,5ꢀdihydroꢀ6'ꢀdeoxybromotopsentin (Figure 1, I) is a natural product isolated
from sponge which is found to have potent cytotoxicity.2 2ꢀAminoꢀβꢀglycosylamines (Figure
1, II) moieties are found in the central core of Nꢀlinked glycoproteins and glycopeptides
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which play key role in cellꢀrecognition and signal transduction processes.3 Oseltamivir
(Figure 1, III)4 is employed for the treatment and prophylaxis of influenza virus A and B
infections. Besides biological activities, these particular compounds can be used as
organocatalysts, ligand in coordination chemistry, and chiral auxiliaries in several important
chemical transformation reactions.5 Direct amino functionalization of alkenes is a potential
route for accessing these systems. During the last few years, several protocols have been
developed for direct aminofunctionalization of olefins under different conditions.6 However,
development of a metalꢀfree protocol for such transformations with a broader substrate scope
and high selectivity is greatly desirable. Recently, we have established that N,NꢀDibromoꢀpꢀ
toluene sulfonamide (TsNBr2)7 is a very powerful and efficient reagent for various organic
transformations.8 In continuation of our work8 on different organic transformations using
TsNBr2, we wish to report herein synthesis of various amino functionalized products from
olefins under a very mild conditions (Scheme 1). This work clearly addresses the dual
behaviour of TsNBr2 as a source of electrophilic bromonium ion as well as a nucleophilc
amine counterpart.
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O
NHTs
R
R1
THF
Br
0-25° C
R1
R
NTs
CH3CN
0-25° C
N
TsNBr2
R1
R
NHTs
R1
CH2Cl2
R
R
Br
0-25° C, N2
NHAc
CH3CN, H2O
r.t.
R1
NHTs
.Scheme 1: Aminofunctionalization of olefins using TsNBr2
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RESULTS AND DISCUSSION
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During our investigation on various organic transformations using TsNBr2, we found
that this reagent is an excellent source of bromonium ion.8c,8d In presence of olefin, it readily
forms cyclic bromonium ion which can further be opened in situ by a suitable nucleophile
added to the reaction system to produce corresponding vicinal bromofunctionalized
product.8c, 8d To begin our venture, we intended to investigate the reaction of olefin with
TsNBr2 in presence of a cyclic oxygen nucleophile, THF. We envisioned that, THF will act a
nucleophile for opening of the cyclic bromonium ion to yield an oxonium ion, which in turn
should be trapped by the NHTs group generated in situ to produce corresponding amino
ethers.9ꢀ12 There are few reports in the literature for opening of cyclic ethers in presence of a
bromine source.9ꢀ12 Thomas et al. developed a strategy for the synthesis of dibromo bicyclic
ethers via bromine assisted ring expansion of unsaturated epoxide.9 A similar strategy was
developed by Jamison et al. to construct some polycyclic ether compound.10 They used NBS
for generation of bromonium ion which assisted epoxide ring opening to produce the desired
product. Braddock et al. reported an intramolecular bromonium ion assisted epoxide ringꢀ
expansions where in situ formed oxonium ion was captured with externally added
nucleophile.11 Based on this concept, Yeung et al. developed a method for aminoalkoxylation
of olefin using NBS and TsNH2 in presence of cyclic ethers.12
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To begin our investigation we have taken styrene as a model substrate to find out the
optimum reaction condition. Results are summarized in Table 1. A reaction was carried out
by adding TsNBr2 (1 mmol) to a stirred solution of styrene (1 mmol) in THF (5 mL) at room
temperature. After two hours of reaction (TLC), the desired aminoether was isolated in 70%
yield along with bromoamine as byꢀproduct with the product ratio of 70:20 (Table 1, entry 1).
Diminishing effect was observed when lesser amount of THF was used. The formation of
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bromoamine is due to the competitive attack of the NHTs group at bromonium ion of original
olefin. So in order to increase the yield of the desired product, the NHTs group must attack at
oxonium intermediate. Next, the reaction was examined by adding TsNBr2 under ice cold
condition and reaction was continued at room temperature. In this case, a marginal
improvement in yield was observed as it prevented the formation of byꢀproduct (2a) to some
extent. Thereafter, the reaction was studied by adding 1ꢀ2 drops of water to the reaction
mixture. Interestingly, this could produce excellent result with 81% yield of aminoether (1a)
within a short span of time. Increasing the amount of TsNBr2 under similar condition (Table
1, entry 5) produced a better result with 87% yield. When dichloromethane (dry) was used as
a solvent, instantaneous formation of bromoamine (2a) was observed as the exclusive product
(Table 1, entry 6, 87%).
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Table 1: Optimization of reaction conditionsa
Ts
N
NHTs
NHTs
Br
O
TsNBr2 (1.2 eqv)
N
+
+
Br
Solvent, H2O (1-2 drops)
3a
2a
1a
0-25 °C
Entry
1
Solvent
TsNBr2
(mmol)
Time
(h)
Temp. Yieldb Yieldb Yieldb
( °C)
of 1a
(%)
70
of 2a
(%)
20
of 3a
(%)
ꢀ
THF (5
mL)
1
2
RT
2
3
THF (2mL)
THF (5 mL)
THF (5
1
1
2.5
2
RT
0ꢀ25 °C
60
75
30
15
ꢀ
ꢀ
4
mL), 1ꢀ2
drops water
THF (5
mL), 1ꢀ2
drops water
CH2Cl2
1
1
1
0ꢀ25 °C
81
trace
ꢀ
5
6
1.2
1.2
0ꢀ25 °C
87
ꢀ
trace
87
ꢀ
ꢀ
Instantaneous 0ꢀ25 °C
(2 mL)
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CHCl3
(2 mL)
DMF
(2 mL)
CH3CN
(5 mL)
CH3CN
(5 mL)
CH3CN
(5 mL)
1.2
1.2
1
30 (min)
0ꢀ25 °C
0ꢀ25 °C
RT
ꢀ
ꢀ
78
NR
ꢀ
30 (min)
ꢀ
9
3
3
3
30
60
71
76
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10
11
1
0ꢀ25 °C
0ꢀ25 °C
ꢀ
ꢀ
Trace
Trace
1.2
aReaction condition: Styrene 1 mmol; bIsolated yield
After optimizing the condition for alkoxyamination reaction, the reaction was to a
variety of olefins. Results are summarized in the Table 2. From the table it can be seen that
the reaction proceeds well with almost all kind of olefins. The reaction is very efficient as it
occurs readily under mild conditions with high yield. In the reaction system, TsNBr2 itself act
as a bromine source as well as nitrogen source. Unlike other methods reported in the
literature,11, 12 this protocol does not require any external amine for alkoxyamination reaction.
Table 2: Synthesis of alkoxyamine from various olefins a.
NHTs
O
TsNBr2 (1.2 eqv)
R1
R1
R
R
THF(5mL) , H2O (1-2 drops)
Br
0-25 °C
1a
O
O
O
O
NHTs
NHTs
NHTs
NHTs
Br
Br
Br
Br
F
Br
Cl
1a, 1h,87%
1c, 1h, 82%
1d, 1h, 84%
1b, 1h, 84%
Br
O
O
Br
NHTs
NHTs
NHTs
Ph
NHTs
O
Ph
Br
O
Br
1f, 1.2h, 81%
1e, 1h, 89%
1h, 1.2h, 80%
1g, 1.2h, 81%
O
TsHN
O
NHTs
Br
Br
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1i, 1.2h, 83%
1j, 2h, 79%
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aReaction condition: TsNBr2 (1.2 mmol), Olefin (1 mmol), THF (5 mL). Water (1ꢀ2 drops), 0ꢀ25 °C;
yields reported refers the isolated yields after chromatographic purification
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Next, we have examined the scope of aminobromination reaction using TsNBr2.
Vicinal haloamino moieties are considered as versatile building blocks in organic synthesis
because of their synthetic potential for further manipulation by replacement of halogen with
diverse nucleophiles. They are synthetic intermediates for functional materials and
biologically active compounds.1a, 13 In the past several decades, a number of procedures have
been developed for vicinal aminobromination using various combinations of reagents and
catalysts, which includes important examples such as N,Nꢀdihalo sulphonamides,7 N,Nꢀdihalo
carbamates,14 Nꢀhalo carbamates,13, 15 Nꢀbromoacetamide,16 N,Nꢀdibromo phosphoramidate,17
19
S,SꢀdimethylꢀNꢀ(pꢀtoluenesulfonyl)ꢀsulfilimine/NBS,18
TsNBr2/TsNH2,
Nꢀmethylꢀpꢀ
22
toluenesulfonamide/NBS20 and cyanamide/NBS,21 KIꢀNBSꢀTsNH2 and others.23ꢀ28 Very
recently, Yeung and his coꢀworkers reported a catalyst and metal free protocol for the
bromoamidation of unactivated olefins using 4ꢀ(trifluoromethyl)benzenesulfonamide and Nꢀ
bromosuccinimide as nitrogen and bromine source.29 In contrast, we have developed a much
simpler protocol for the synthesis of aminobromine using a single reagent (Table 1, entry 6).
The scope of this methodology was examined by using various types of olefins like
substituted styrenes, α,β unsaturated cinnamic esters, chalcone, aliphatic olefin, cyclohexene,
stilbene etc. (Table 3). From the table, it can be seen that all kind of olefins could be
transformed into the desired aminobromines with high yields. The reaction was found to be
completely stereoꢀ and regioselective. The reaction proceeds via a threeꢀmembered cyclic
bromonium ion intermediate due to electrophilic addition of the Br+ ion (generated from
TsNBr2) onto the olefin.8c,d This intermediate undergoes ring opening by the amine
nucleophile via a SN2 pathway, which results in the antiꢀselectivity of the aminobromine
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adduct. Nucleophilic opening of the cyclic bromonium intermediate is most likely from the
more positive βꢀposition.8c,d
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Table 3: Synthesis of aminobromine with different olefinsa
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Br
TsNBr2 (1.2 equv)
R1
R
R1
R
NHTs
CH2Cl2 (2 mL), 0-25 °C
2a
NHTs
Br
NHTs
Br
TsHN
Br
Br
NHTs
Cl
2c, 78%
2a, 87%
2b, 90%
2d, 77%
H
H
NHTs
Br
NTs
O
NTs O
OC2H5
OCH3
Br
NHTs
Br
Br
Cl
2h, 82%
2g, 79%
2e, 79%
2f, 80%
TsHN
Br
Br
H
NTs
O
Br
NHTs
NHTs
Br
Cl
2i, 86%
2k, 88%
2j, 90%
2l, 83%
Ph
O
Br
O
O
Br
NHTs
NHTs
O
Ph
Ph
2n, 88%
2m, 80%
aReaction condition: Olefin (1 mmol), TsNBr2 (1.2 mmol), CH2Cl2 (2 ml), 0ꢀ25 °C, 10 min; bisolated
yield
While examining the reactions of TsNBr2, we found that, olefins when treated with
TsNBr2 in acetonitrile, produce imidazolines (Table 1, entry 9ꢀ11). Imidazolines are another
important class of compounds that exhibits high therapeutic importance. Several methods
have been reported for the synthesis of imidazolines.30 [3+2] Cycloaddition of Nꢀ
tosylaziridines with nitriles in presence of several Lewis acids has been found to be the most
efficient methods reported so far.31 Ritter reaction with nitrile is another important
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methodology for the synthesis of imidazolines.31d, 32 We found that the treatment of styrene
with TsNBr2 in acetonitrile results in the formation of imidazoline as the major product
product (Table 1, Entry 9). In this instance also, we have isolated corresponding
aminobromine as a side product. Addition of TsNBr2 to an ice cold solution of styrene in
moist acetonitrile and continuation of the reaction at room temperature could improve the
yield of desired imidazoline up to 71 % with trace amount of the side product. One important
observation we made is that the use of dry acetonitrile increases the formation of bromoamine
which has also been noticed in case of aminoether formation reaction. Further increase of the
amount of TsNBr2 from 1 mmol to 1.2 mmol could bring up the yield of imidazoline to 76 %
(Table 1, Entry 11). After obtaining the optimized reaction condition, the process was
extended for different olefins and the results are shown in Table 4. In this case, CH3CN acts
as a nucleophile to form an intermediate nitronium ion which further reacts with in situ
generated NHTs group to produce the desired product via the formation of a bromoamidine.32
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Table 4: Synthesis of imidazoline and bromoamidine from different olefins a
Ts
N
5
6
7
TsNBr2 (1.2 eqv)
N
8
9
CH3CN( 5 mL), 0-25° C
3a
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NTs
NTs
NTs
NTs
N
N
N
N
Cl
F
Br
3a, 76%, 3h
3b, 75%, 3h
3c, 73%, 3h
3d, 77%, 3h
Ts
N
Ts
N
NTs
N
TsN
N
Ph
N
N
Ph
Ph
3h, 80%, 2h
3f, 81%, 3h
3g, 77%, 3h
3e, 76%, 3h
Br
Br
NTs
N
NTs
N
N
NTs
H
H
3k, 85%, 30 min
3j, 86%, 30min
3i, 79%, 2h
aReaction condition: TsNBr2 (1.2 mmol) , Styrene (1 mmol), CH3CN (5 mL), 0ꢀ25° C. bIsolated yields.
Interestingly, when the reaction was carried out with cyclohexene and cyclooctene,
intermediate bromoamidine was isolated as the sole product. However, in all other cases,
imidazolines were isolated as the lone product. During the purification of imidazoline, we
observed that, column chromatography over silicagel results in the formation of a mixture of
imidazoline and Nꢀ(1ꢀphenylꢀ2ꢀ(tosylamino)ethyl)acetamide. However, if the reaction
mixture is kept over silicagel (in the column) for 24h, corresponding diamine derivative
forms as the single product (Scheme 2).
NHCOCH3
TsNBr2 (1.2 eqv)
NHTs
CH3CN (5 mL) 0-25° C,
4a
Colum Chromat (SiO2)
Scheme 2: Formation Nꢀacetyl, N'ꢀtosyl diamine from styrene
Hence, in this case, chromatographic purification was performed over silicagel by adding
little amount of diethyl amine to the eluting solvent to isolate imidazolines exclusively.
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Hydrolytic disintegration of imidazolines to corresponding diamine is known in the
literature.33 1,2ꢀDiamino compounds have received significant interest as they are present in
numbers of natural products with profound biological activity. 1,2ꢀDiamines can also be used
as ligand as well as an organocatalysts in many reactions. Efforts were made to design and
synthesis of this particular substrate during the last few years. Kumar and Ramesh had
developed a procedure for diamination of glycals with chloramineꢀT in presence of iodine as
catalyst at 0 °C to afford 2ꢀaminoꢀbꢀglycosylamine derivatives.34 This procedure is restricted
to glycals only. Usually, the transformation of olefin to diamine is carried out with the aid of
a metal catalyst.35 This protocol has also been extended for intramoleculat diamination
reaction to produce some interesting heterocycles.35 Muñiz et al. synthesized some diamino
compounds from internal alkenes using Pd as a catalyst using two different amine sources.36
They utilized a combination of a ditosyl amine and saccarine or phthalimide in presence of a
hypervalent iodine oxidant to achieve the transformation. Later, the same group had utilized
iodine (III) reagent for similar transformations.37 Thus one pot synthesis of 1,2ꢀdiamine
derivatives from olefin is highly desirable. To look for the possibilities for a direct one pot
conversion of olefin to corresponding Nꢀacetyl,N'ꢀtosyl diamine, we examined the reaction of
styrene at higher temperature. The reaction was carried out at 80 °C in presence of HCl,
H2SO4 and K2CO3 as additive (3 mole equiv). None of these efforts could produce the
expected diamine derivative. After, extensive study of the reaction under varied conditions, it
was finally found that when olefin (1 mmol) is treated with TsNBr2 (1.5 mmol) in presence of
CH3CN (8 mL) and H2O (1 mL) produced the corresponding diamine derivative with
reasonably high yield. Best result was found when the reaction was stirred for 3 hours at
room temperature. However, in case of cyclohexene, it is necessary to carry out the reaction
at 80 °C to achieve the best results. The results are summarized in table 5.
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Table 5: Synthesis of diamine derivative from various olefinsa
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NHCOCH3
TsNBr2 (1.5 eqv.)
R1
R1
R
R
CH3 CN (8 mL), H2O (1 mL)
8
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NHTs
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NHCOCH3
NHTs
NHCOCH3
NHCOCH3
NHTs
NHCOCH3
NHTs
NHTs
Cl
F
Br
4a, 85%
4b, 85%
4c, 82%
4d, 80%
NHCOCH3
NHCOCH3
NHAc
NHCOCH3
Ph
Ph
NHTs
NHTs
NHTs
NHTs
4g, 82%
4f, 78%
4h, 80%
4e, 85%
aReaction condition: TsNBr2 (1.5 mmol) , Olefin (1 mmol), CH3CN (8 mL), H2O (1 mL); Isolated yield
Thus, this procedure could produce Nꢀacetyl,N'ꢀtosyl diamine derivatives directly from olefin
under a very mild reaction condition. In general, the reaction efficiently produced
corresponding diamines at room temperature with high yield. Formation of diamine via the
ring opening of inꢀsitu generated aziridine is known in the literature.34a Earlier, we have
reported an efficient protocol for the synthesis of aziridine from olefin by treating with
TsNBr2 in presence of potassium carbonate under mild reaction conditions.8e We believed
that nucleophilic NHTsꢀgroup generated inꢀsitu from TsNBr2 should take part in ring opening
of aziridine to provide 1, 2ꢀdiamines. Hence, the reaction was further investigated to explore
the possibility of synthesis of N,N′ꢀditosyl diamine derivatives. Accordingly, under a similar
reaction condition that holds for aziridination, styrene was treated with two molar equivalent
of TsNBr2 in presence of K2CO3. In a typical reaction, a solution of styrene (1 mmol) and
K2CO3 (5 mmol) in ethylacetate (10 mL) was treated with TsNBr2 (2 mmol) under nitrogen
atmosphere at room temperature. The result was not found to be encouraging in this case,
even after 12h of reaction. However, diamine was isolated in 60% yield when the reaction
was carried out at 60 °C using the same concentration of the reagents. Further increase of
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TsNBr2 amount to 2.4 equivalents could improve the yield of the product and the reaction
was found to complete within 2h. However, the yields of the products were found to be low.
Interestingly, sugar molecules showed better reactivity profile and corresponding product
could be produced at room temperature with moderate yield. Few representative examples for
the synthesis of N,N′ꢀditosyl diamine derivatives are included in Table 6. The reaction is
believed to proceed through an initial formation of aziridine8e which undergoes ring opening
via a nucleophilic attack by NTs group.34a
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Table 6: Synthesis of diamines with various olefinsa
NHTs
TsNBr2 (2.4 eqv)
R1
R1
R
R
NHTs
K2CO3 (5 eqv), EtOAc, N2
5
O
S O
NH
O
S
N
O
H
5a, 70%, 2h, 60° C
O
S
NH
O
H
N
O
S
O
S
O
O
O
O
NH
S
NH
O
O
5c, 67%, 3h, RT
AcO
OAc OAc
5b, 74%, 2h,
RT
aReaction condition: TsNBr2 (1.5 mmol) , Olefin (1 mmol),
EtOAc (10 mL); Isolated yield
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CONCLUSION
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In summary, we have developed an efficient methodology for the synthesis of variety of
compounds via amino functionalization of olefins using TsNBr2. Under different reaction
conditions aminoether, amino bromine, imidazoline and diamine could be synthesized using
this reagent. The reactions are very simple which can be carried out under mild conditions.
The yields of respective products are also high. The reagent TsNBr2 itself act as an
electrophilic bromine source as well as the source of nucleophilic nitrogen. No external
amine is required for this aminofunctionalization reaction.
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EXPERIMENTAL SECTION
General Remarks. All reagents and starting materials were purchased from commercial
sources. Chemical shifts in NMR spectral data are given in δ units relative to the
tetramethylsilane (TMS) signal as an internal reference in CDCl3. Coupling constants (J) are
reported in hertz. Chromatographic purification was performed using flash chromatography
over a manually packed column containing silica gel (230ꢀ400 mesh).
General procedure for the synthesis of alkoxyamine using various olefins (1a-1j):
To a solution of olefin (1 mmol) in THF (5 mL) and water (1ꢀ2 drops), TsNBr2 (1.2 mmol)
was added in small proportions over a period of 20 min under ice cold condition and the
reaction was continued at room temperature for appropriate time (TLC). The excess solvent
was removed in rotary evaporator and sodium thiosulfate (100 mg approx.) was added
followed by the addition of water (5 mL). The reaction mixture was stirred for another 5 min
and extracted with ethyl acetate (3 x 10 mL). The combined organic extract was dried over
anhydrous sodium sulphate and concentrated under reduced pressure. The crude product was
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purified by flash chromatography on silica gel (230–400 mesh) with petroleum ether/ethyl
acetate as eluent to obtain pure alkoxyamine product.
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4ꢀ(2ꢀBromoꢀ1ꢀphenylethoxy)ꢀNꢀtosylbutanꢀ1ꢀamine (1a): Colourless gum (370 mg, 87%
yield); 1HNMR (CDCl3, 300 MHz): δ 7.76 (d, J = 7.8 Hz, 2H), 7.41ꢀ7.23 (m, 7H), 5.11 (t, J
= 6Hz, 1H), 4.45ꢀ4.37 (m, 1H), 3.51ꢀ3.39 (m, 2H), 3.36ꢀ3.26 (m, 2H), 3.02ꢀ2.88 (m, 2H),
2.41(s, 3H), 1.65ꢀ1.53 (m, 4H); 13C NMR (CDCl3, 75 MHz): δ 143.3, 139.4, 137.0, 129.7,
128.7, 128.5, 127.1, 126.7, 82.0, 68.9, 42.9, 36.5, 26.7, 26.5, 21.5; HRMS (QTOFꢀESI+)
calcd for C19H24BrNO3S [M + Na]+:448.0552; found : 448.0574.
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4ꢀ(2ꢀBromoꢀ1ꢀ(4ꢀchlorophenyl)ethoxy)ꢀNꢀtosylbutanꢀ1ꢀamine (1b): Yellow gum (387 mg,
1
84%); HNMR (CDCl3, 300 MHz): δ 7.73 (d, J = 8.4, 2H), 7.33ꢀ7.25 (m, 4H), 7.20 (d, J =
8.4 Hz), 5.36ꢀ5.20 (m, 1H), 4.43ꢀ4.32 (m, 1H), 3.50ꢀ3.33 (m, 2H), 3.31ꢀ3.21 (m, 2H), 2.99ꢀ
2.85 (m, 2H), 2.39 (s, 3H), 1.66ꢀ1.46 (m, 4H); 13C NMR (CDCl3, 75 MHz): δ 143.1, 137.7,
136.7, 133.9, 129.5, 128.6, 127.9, 126.9, 80.8, 68.7, 42.7, 35.9, 26.3, 26.2, 21.3; HRMS
(QTOFꢀESI+) calcd for C19H23BrClNO3S [M + Na]+:482.0168; found: 482.0165.
4ꢀ(2ꢀBromoꢀ1ꢀ(4ꢀfluorophenyl)ethoxy)ꢀNꢀtosylbutanꢀ1ꢀamine (1c): Yellow gum.( 364 mg,
82%); 1HNMR (CDCl3, 300 MHz): δ 7.75 (d, J = 8.1 Hz, 2H), 7.36ꢀ 7.21 (m, 4H), 7.05 (d, J
= 8.1, 2H), 5.08ꢀ4.98 (m, 1H), 4.46ꢀ4.36 (m, 1H), 3.52ꢀ 3.36 (m, 2H), 3.35ꢀ3.28 (m, 2H),
3.06ꢀ2.83 (m, 2H), 2.41(s, 3H), 1.74ꢀ1.47(m, 4H); 13C NMR (CDCl3, 75 MHz): δ 162.6 ( 1JCF
= 245.5 Hz), 143.2, 136.9, 135.0 (4JCF = 3.3 Hz), 129.6, 128.3 (3JCF = 7.6 Hz), 127.0, 115.6
(2JCF = 21.3 Hz), 81.2, 68.8, 42.8, 36.2, 26.6, 26.4, 21.4; HRMS (QTOFꢀESI+) calcd for
C19H23BrFNO3S [M + Na]+: 466.0458; found: 466.0458.
4ꢀ(2ꢀBromoꢀ1ꢀ(4ꢀbromophenyl)ethoxy)ꢀNꢀtosylbutanꢀ1ꢀamine (1d): Colourless gum.(424
mg, 84%); 1HNMR (CDCl3, 300 MHz): δ 7.75 (d, J = 8.1 Hz, 2H), 7.48 (d, J = 7.8 Hz, 2H),
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7.30 (d, J = 7.5 Hz, 2H), 7.16 (d, J = 7.8 Hz, 2H), 5.14ꢀ4.84 (m, 1H), 4.46ꢀ4.31 (m, 1H),
3.52ꢀ3.24 (m, 4H), 3.02ꢀ2.85 (m, 2H), 2.42 (s, 3H), 1.68ꢀ1.49 (m, 4H); 13C NMR (CDCl3, 75
MHz): δ 143.2, 138.3, 136.9, 131.8, 129.6, 128.4, 127.0, 122.4, 81.2, 68.9, 42.8, 35.9, 26.6,
26.5, 21.5; HRMS (QTOFꢀESI+) calcd for C19H23Br2NO3S [M + Na]+: 527.9643; found :
527.9638.
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4ꢀ(2ꢀBromoꢀ1ꢀphenylpropoxy)ꢀNꢀtosylbutanꢀ1ꢀamine (1e): Colourless gum ( 391 mg, 89%);
1H NMR (CDCl3, 300 MHz): δ 7.76 (d, J = 7.8 Hz, 2H), 7.49 7.20 (m, 7H), 5.19ꢀ4.97 (m,
1H), 4.52ꢀ4.34 (m, 1H), 4.19 (t, J = 6Hz, 1H), 3.54ꢀ3.22 (m, 2H), 3.15ꢀ2.87 (m, 2H), 2.41 (s,
3H), 1.79ꢀ1.51 (m, 7H); 13C NMR (CDCl3, 75 MHz): δ 143.2, 138.7, 136.9, 129.6, 128.2,
128.0, 127.2, 127.0, 85.5, 69.1, 52.6, 42.8, 26.6, 26.4, 21.4, 20.3; HRMS (QTOFꢀESI+) calcd
for C20H26BrNO3S [M + Na]+: 462.0709; found : 462.0709.
4ꢀ((1S, 2S)ꢀ2ꢀBromocyclohexyloxy)ꢀNꢀtosylbutanꢀ1ꢀamine (1f):12 Light yellow gum (327
1
mg, 81%); HNMR (CDCl3, 300 MHz): δ 7.75 (d, J = 7.8Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H),
5.09ꢀ4.96 (m, 1H), 3.95ꢀ3.81 (m, 1H), 3.63ꢀ3.39 (m, 2H), 3.29ꢀ3.17 (m, 1H), 3.04ꢀ2.89 (m,
2H), 2.42 (s, 3H), 2.35ꢀ2.23 (m, 1H), 2.16ꢀ2.04 (m, 1H), 1.79ꢀ1.52(m, 7H), 1.34ꢀ1.20 (m,
3H); 13C NMR (CDCl3, 75 MHz): δ 143.1, 136.9, 129.6, 127.0, 82.1, 68.9, 55.9, 42.9, 35.9,
30.9, 27.0, 26.5, 25.6, 23.4, 21.5.
4ꢀ(2ꢀBromocyclopentyloxy)ꢀNꢀtosylbutanꢀ1ꢀamine (1g): Light yellow gum (316 mg, 81%);
1HNMR (CDCl3, 300 MHz): δ 7.72(d, J = 7.8 Hz, 2H), 7.28 (d, J = 7.8 Hz, 2H), 5.28 (t, J =
5.4 Hz, 1H), 4.16ꢀ4.07 (m, 1H), 4.00ꢀ3.90 (m, 1H), 3.47 ꢀ3.28 (m, 2H), 2.97ꢀ2.83 (m, 2H),
2.40 (s, 3H), 2.31ꢀ1.86 (m, 4H), 1.83ꢀ1.63 (m, 2H), 1.59ꢀ1.45 (m, 4H); 13 C NMR (CDCl3, 75
MHz): δ 143.1, 136.8, 129.5, 126.9, 87.9, 68.8, 54.0, 42.8, 34.5, 29.7, 26.7, 26.6, 21.5, 21.4.
HRMS (QTOFꢀAPCI+) calcd for C16H24BrNO3S [M + H]+: 390.0739; found 390.0745.
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4ꢀ(2ꢀBromoꢀ1, 2ꢀdiphenylethoxy)ꢀNꢀtosylbutanꢀ1ꢀamine (1h): White solid (402 mg, 80%);
mp (92ꢀ94 °C); 1HNMR (CDCl3, 300 MHz): δ 7.72 (d, J = 7.8 Hz, 2H), 7.47ꢀ7.16 (m, 12H),
4.97 (d, J = 7.2 Hz, 1H), 4.65 (d, J= 6.6 Hz, 1H), 4.60ꢀ4.39 (m, 1H), 3.36ꢀ3.08 ( m, 2H),
2.89ꢀ2.72 (m, 2H), 2.43 (s, 3H), 1.45ꢀ1.24 (m, 4H); 13C NMR (CDCl3, 75 MHz): δ 143.2,
138.9, 138.7, 136.9, 129.6, 128.7, 128.3, 128.1, 128.1, 127.7, 127.0, 85.7, 68.9, 56.8, 42.7,
26.3, 26.1, 21.5. HRMS (QTOFꢀESI+) calcd for C25H28BrNO3S [M + Na]+:524.0871; found
524.0861.
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4ꢀ(1ꢀBromoꢀ2, 3ꢀdihydroꢀ1Hꢀindenꢀ2ꢀyloxy)ꢀNꢀtosylbutanꢀ1ꢀamine (1i): Yellow gum (364
1
mg, 83%); HNMR (CDCl3, 300 MHz): δ 7.68 (d, J = 8.4 Hz, 2H), 7.39ꢀ7.17 (m, 6H), 5.04ꢀ
4.87 (m, 2H), 4.45ꢀ 4.32 (m, 1H), 3.84ꢀ3.71 (m, 1H), 3.67ꢀ3.61 (m, 2H), 3.20 (dd, J = 16.5,
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5.4 Hz, 1H), 2.99ꢀ2.89 (m, 2H), 2.41 (s, 3H), 1.67ꢀ1.55 (m, 4H); C NMR (CDCl3, 75
MHz): δ 143.3, 140.4, 140.1, 136.9, 129.7, 129.2, 127.3, 127.0, 125.1, 124.8, 90.5, 69.7,
51.3, 42.9, 41.3, 27.1, 26.6, 21.5. HRMS (QTOFꢀESI+) calcd for C20H24BrNO3S [M + Na] +:
460.0558; found 460.0561.
4ꢀ(1ꢀBromoꢀ2ꢀmethylheptanꢀ2ꢀyloxy)ꢀNꢀtosylbutanꢀ1ꢀamine (1j): Yellow gum (343 mg,
79%); 1HNMR (CDCl3, 300 MHz): δ 7.74 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.1 Hz, 2H), 5.07
(t, J = 5.4Hz, 1H), 3.40ꢀ3.33 (m, 2H), 3.32ꢀ3.24 (m, 2H), 2.94 (t, J = 6 Hz, 2H), 2.41 (s, 3H),
1.64ꢀ1.48 (m, 6H), 1.34ꢀ1.24 (m, 6H), 1.20 (s, 3H), 0.88 (t, J = 6 Hz, 3H); 13 C NMR (CDCl3,
75 MHz): δ 143.1, 137.0, 129.6, 127.0, 75.5, 60.7, 43.0, 39.6, 36.4, 32.0, 27.1, 26.7, 23.0,
22.5, 22.0, 21.5, 14.0; HRMS (QTOFꢀESI+) calcd for C19H32BrNO3S [M + Na] +: 456.1184;
found 456.1195.
General procedure for synthesis of aminobromine (2a-2n):
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To a solution of olefin (1 mmol) in dichloromethane (2 ml), TsNBr2 (1.2 mmol) were added
in portions under nitrogen atmosphere and ice cold conditions. Instantaneous reaction took
place. Reaction was stirred for another 10 minutes at room temperature. After completion of
the reaction sodium thiosulfate was added and the reaction mixture was stirred for 15
minutes. The reaction mixture was taken up in ethyl acetate, dried over anhydrous sodium
sulfate, and concentrated. The crude product was purified by flash chromatography on silica
gel (230–400 mesh) with petroleum ether/ethyl acetate as eluent.
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2ꢀBromoꢀ1ꢀphenylꢀNꢀtosylethanamine (2a):38 White solid (307 mg, 87%); mp (167ꢀ168 °C);
1HNMR (CDCl3, 300 MHz): δ 7.64 (d, J = 8.1 Hz, 2H ), 7.31ꢀ7.18 (m, 5H), 7.17ꢀ7.09 (m,
2H), 5.31 ( d, J = 6.6 Hz, 1H), 4.66ꢀ4.48 (m,1H,), 3.66ꢀ3.50 (m, 2H) 2.40 (s, 3H); 13C NMR
(CDCl3, 75 MHz): δ 143.6, 137.6, 136.8, 129.5, 128.6, 128.3, 127.2, 126.7, 57.9, 36.7, 21.5.
2ꢀBromoꢀ 1ꢀ(4ꢀchlorophenyl)ꢀNꢀtosylethanamine (2b):39 White solid (349 mg, 90%); mp
1
(147ꢀ148 °C); HNMR (CDCl3, 300 MHz): δ 7.61 (d, J = 7.8 Hz, 2H), 7.28ꢀ7.16 (m, 4H),
7.05 (d, J = 8.4 Hz), 5.52 (d, J = 6.3 Hz, 1H), 4.59ꢀ4.54 ( m, 1H ), 3.53 (d, J = 5.7 Hz, 2 H)
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2.41 (s, 3H); C NMR (CDCl3, 75 MHz): δ 143.8, 136.6, 136.1, 134.2, 129.6, 128.7, 128.1,
127.1, 57.3, 36.3, 21.5.
2ꢀBromoꢀNꢀtosylcyclohexanamine (2c):38 White solid (258mg, 78%); mp (115ꢀ116 °C);
1HNMR (CDCl3, 300 MHz): δ 7.79 (d, J = 8.1 Hz, 2H), 7.28 (d, J = 8.1, 2H), 5.55 (d, J = 5.1
Hz, 1H), 3.90ꢀ3.85 (m, 1H), 3.23ꢀ3.19 (m, 1 H) 2.40 (s, 3H ), 2.31ꢀ2.20 (m, 1H), 2.20ꢀ2.05
(m, 1H), 1.83ꢀ1.69 (m, 1H), 1.67ꢀ1.55 (m, 2H), 1.32ꢀ1.25 (m, 3H); 13C NMR (CDCl3, 75
MHz): δ 143.3, 137.2, 129.5, 127.1, 58.3, 54.8, 35.4, 32.4, 24.9, 23.2, 21.4.
2ꢀBromoꢀ1, 2ꢀdiphenylꢀNꢀtosylethanamine (2d):38 White solid (331 mg, 77%); mp (158ꢀ159
°C);1HNMR (CDCl3, 300 MHz): δ 7.45 (d, J = 6.3 Hz, 2H), 7.26ꢀ7.01 (m, 10 H), 6.90 (d, J =
7.5 Hz, 1H), 5.50 (d, J = 7.8 Hz, 1H), 5.16 (d, J = 6.3 Hz, 1H), 4.83ꢀ4.78 (m, 1H), 2.33 (s,
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3H); 13C NMR (CDCl3, 75 MHz): δ 143.1, 136.9, 136.3, 129.2, 129.1, 128.7, 128.6, 128.4,
128.0, 127.7, 127.6, 127.0, 63.1, 58.1, 21.4.
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Ethylꢀ2ꢀbromoꢀ3ꢀphenylꢀ3ꢀ(tosylamino)propanoate (2e):38 White solid (336mg, 79%); mp
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(174ꢀ176 °C); HNMR (CDCl3, 300 MHz): δ 7.65 (d, J = 7.8 Hz, 2H), 7.33ꢀ7.22 (m, 7 H),
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5.24 (d, J = 9.9 Hz, 1H), 5.14 (d, J = 6.3 Hz, 1H), 4.49ꢀ4.43 (m, 1 H), 4.02ꢀ3.88 (m, 2H),
2.41 (s, 3H), 1.11 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 75 MHz): δ 168.6, 143.8, 136.4,
136.2, 129.6, 129.1, 128.3, 127.3, 62.4, 61.8, 51.7, 21.5, 13.8.
Methylꢀ2ꢀbromoꢀ3ꢀ(4ꢀchlorophenyl)ꢀ3ꢀ(tosylamino)propanoate (2f):39,40 White solid (355
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mg, 80%); mp (111ꢀ112 °C); HNMR (CDCl3, 300 MHz): δ 7.56 (d, J = 7.8 Hz, 2H), 7.27ꢀ
7.19 (m, 6H), 5.67 (d, J = 7.8 Hz, 1H), 5.01 (d, J = 8.4 Hz, 1H), 4.45 (t, J = 9.3 Hz, 1H), 3.56
(s, 3H), 2.42 (s, 3H); 13C NMR (CDCl3, 75 MHz): δ 169.6, 143.9, 136.1, 134.9, 134.8, 132.2,
129.5, 128.7, 127.1, 61.6, 52.8, 50.0, 21.5.
4ꢀBromoꢀNꢀtosylhexanꢀ3ꢀamine (2g):41 White solid (263 mg, 79%); mp (99ꢀ100 °C);
1HNMR (CDCl3, 400 MHz): δ 7.57 (d, J = 7.6 Hz, 2H), 7.11 (d, J = 7.6 Hz, 2H), 4.59 (d, J =
8.8 Hz, 1H), 3.64 (m,1H,), 2.97 (t, J = 9.6 Hz, 1H), 2.24 (s, 3H), 1.58ꢀ1.54 (m, 2H), 1.36ꢀ1.34
(m, 2H), 0.76 (t, J = 7.2 Hz, 3H), 0.61 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz): δ
143.9, 138.6, 130.1, 127.4, 65.6, 59.3, 29.7, 23.5, 21.9, 13.1, 10.5.
2ꢀ Bromoꢀ1ꢀphenylꢀNꢀtosylpropaneꢀ1ꢀamine (2h):25 White solid (301 mg, 82%); mp (133ꢀ
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135 °C); HNMR (CDCl3, 300 MHz): δ 7.53 (d, J = 8.4 Hz, 2H), 7.23ꢀ7.13 (m, 3H), 7.12ꢀ
7.05 (m, 4H), 5.46 ( d, J = 7.8 Hz, 1H), 4.51ꢀ4.37 (m, 2H), 2.34 (s, 3H), 1.53 (d, J = 6.3 Hz,
3H,); 13C NMR CDCl3, 100 MHz): δ 143.7, 137.4, 136.3, 129.7, 128.4, 128.2, 127.4, 62.7,
54.5, 54.3, 22.6, 21.8.
1ꢀBromoꢀ2,3ꢀdihydroꢀNꢀtosylꢀ1Hꢀindaneꢀ2ꢀamine (2i):38 White solid (314 mg, 86%); mp
1
(167ꢀ168° C); HNMR (CDCl3, 400 MHz): δ 7.79 (d, J = 8 Hz, 2H), 7.29 (d, J = 8 Hz, 2H),
7.20ꢀ7.18 (m, 1H), 7.17ꢀ7.11 (m, 2H), 7.03 (d, J = 8 Hz, 1H), 4.87ꢀ4.83 (m, 1H), 4.67 (d, J =
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7.6 Hz, 1H), 4.27ꢀ4.22 (m, 1H), 3.51 (dd, J = 16.4 , 7.2, Hz, 1H), 3.12 (dd, J = 16.8 , 5.6 Hz
1H), 2.40 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 144.0, 140.4, 139.4, 137.5, 130.0, 129.5,
128.0, 127.6, 125.0, 124.8, 67.3, 51.9, 41.3, 21.8.
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2ꢀBromoꢀ1,2,3,4ꢀtetrahydroꢀNꢀtosylnaphthalenꢀ1ꢀamine (2j):42 White solid (342 mg, 90%);
mp (135ꢀ137 °C) 1HNMR (CDCl3, 300 MHz): δ 7.83 (d, J = 7.8 Hz, 2H), 7.40 (d, J = 7.8 Hz,
2H), 7.33ꢀ 6.95 (m, 3H), 6.47 (d, J = 7.5 Hz, 1H), 4.83 (d, J = 4.2 Hz, 1H), 4.79ꢀ4.65 (m,
1H), 4.56ꢀ4.40 (m,1H), 3.19ꢀ2.99 (m, 1H), 2.88ꢀ 2.68 (m, 1H), 2.50 (s, 3H), 2.46ꢀ2.32
(m,1H), 2.21ꢀ2.05 (m, 1H); 13C NMR (CDCl3, 100 MHz): δ 144.0, 136.7, 135.6, 131.3,
130.0, 129.6, 129.2, 128.5, 127.3, 126.8, 57.0, 51.0, 24.7, 24.5, 21.7.
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1ꢀBromoꢀNꢀtosyloctanꢀ2ꢀamine (2k):41 Colourless gum (318 mg, 88%); HNMR (CDCl3,
300 MHz): δ 7.75 (d, J = 7.8 Hz, 2H), 7.32 (d, J = 7.8 Hz, 2H), 5.04ꢀ4.86 (m, 1H), 4.06ꢀ3.88
(m, 1H), 3.43ꢀ3.34 (m, 1H), 3.30ꢀ3.02 (m, 1H), 2.43 (s, 3H), 1.84ꢀ1.65 (m, 2H), 1.37ꢀ1.04
(m, 8H), 0.84 (t, J = 9.6 Hz, 3H); 13C NMR (CDCl3, 75 MHz): δ 143.7, 136.8, 129.8, 127.0,
55.5, 49.5, 36.0, 31.5, 28.4, 27.1, 25.2, 22.5, 21.5, 14.0.
2ꢀBromoꢀ3ꢀ(4ꢀchlorophenyl)ꢀ1ꢀphenylꢀ3ꢀ(tosylamino)propanꢀ1ꢀone (2l):43 White solid (408
mg, 83%); 1HNMR (CDCl3, 300 MHz): δ 7.86 (d, J = 7.5 Hz, 2H), 7.62 (t, J = 7.5 Hz, 1 H),
7.56ꢀ7.38 (m, 4 H), 7.27ꢀ7.11 (m, 4H), 7.01 (d, J = 7.8 Hz, 2H ), 5.70 (d, J = 9.9 Hz, 1 H),
5.49 (t, J = 8.4 Hz, 1H), 5.04 (d, J = 8.6 Hz, 1H), 2.29 (s, 3H); 13C NMR (CDCl3, 75 MHz): δ
196.7, 143.7, 136.5, 135.1, 135.0, 134.9, 134.3, 129.8, 129.4, 128.9, 128.7, 128.6, 126.9,
60.3, 50.2, 21.4.
4,5ꢀBis(benzyloxy)ꢀ6ꢀ((benzyloxy)methyl)ꢀ2ꢀbromoꢀtetrahydroꢀNꢀtosylꢀ2Hꢀpyranꢀ3ꢀamine
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(2m): Semi solid (532 mg, 80 %); H NMR (CDCl3, 300 MHz): δ 7.82 (d, J = 8.1 Hz, 2H),
7.38ꢀ7.19 (m, 17H), 5.62 (d, J = 9.3 Hz, 1H), 4.99ꢀ4.77 (m, 4H), 4.57ꢀ4.31 (m, 3H), 3.75ꢀ
3.60 (m, 4H), 3.47ꢀ3.39 (m, 2H), 2.37 (s, 3H); 13C NMR (CDCl3, 75 MHz): δ 143.3, 138.2,
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137.6, 129.6, 129.2, 128.3, 128, 127.9, 127.8, 127.7, 127.3, 125.9, 85.8, 84.8, 78.4, 76.4,
+
76,74.9, 73.4, 70.9, 67.9, 51.8, 21.4; LCMS (ESI) calcd for C34H36 BrN O6S [M +Na ] :
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688.1344; found 688.8. Anal. Calcd (%) for C34H36BrNO6S: C, 61.26; H, 5.44; N, 2.10;
Found: C, 61.37; H, 5.30; N, 2.01.
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2ꢀBromoꢀNꢀtosylcyclopentanamine (2n):27 White solid (279 mg, 88%); mp (72ꢀ75 °C); 1H NMR
(CDCl3, 300 MHz): δ 7.78 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.1Hz, 2H), 5.25 ( d, J = 5.7 Hz,
1H), 4.16ꢀ 4.07 ( m, 1H), 3.76ꢀ3.62 (m, 1H), 2.44 (s, 3H), 2.30ꢀ2.10 (m, 2H), 2.01ꢀ1.91 (m,
1H), 1.85ꢀ1.71 (m, 2H), 1.50ꢀ1.34 (m, 1H); 13C NMR (CDCl3, 75 MHz): δ 143.8, 136.8,
129.8, 127.3, 62.9, 54.3, 34.0, 30.6, 21.6, 21.3.
General procedure for the synthesis imidazoline and bromoamidine (3a-3k):
To a solution of olefin (1 mmol) in CH3CN (5 mL), TsNBr2 (1.2 mmol) was added in small
proportions over a period of 20 min under ice cold condition and the reaction was continued
at room temperature for appropriate time (TLC). The excess solvent was removed in rotary
evaporator and sodium thiosulfate (200 mg approx) was added followed by the addition of
water (5 mL). The reaction mixture was stirred for another 5 min and extracted with ethyl
acetate followed by dried over anhydrous sodium sulphate, and concentrated under reduced
pressure. The crude product was purified by flash chromatography on silica gel (230–400
mesh) with a mixture of petroleum ether and ethyl acetate (with a few drops of diethyl amine)
as eluent to obtain the pure product.
4, 5ꢀDihydroꢀ2ꢀmethylꢀ4ꢀphenylꢀ1ꢀtosylꢀ1Hꢀimidazole (3a):44 White solid ( 238 mg, 76%);
mp (100ꢀ102°C); 1HNMR (CDCl3, 300 MHz): δ 7.74 (d, J = 8.1 Hz, 2H), 7.34 (d, J = 8.1 Hz,
2H), 7.30ꢀ7.20 (m, 3H), 7.10ꢀ6.98 (m, 2H), 4.97 (t, J = 9 Hz, 1H), 4.17 (t, J = 9.9Hz, 1H),
3.62 (t, J= 7.8 Hz, 1H), 2.45 (s, 3H), 2.39 (d, J = 1.5 Hz, 3H); 13 C NMR (CDCl3, 75 MHz): δ
156.3, 144.7, 141.4, 134.9, 130.0, 128.7, 128.6, 127.5, 127.1, 126.3, 66.5, 55.4, 21.5, 16.7.
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4ꢀ(4ꢀChlorophenyl)ꢀ4, 5ꢀdihydroꢀ2ꢀmethylꢀ1ꢀtosylꢀ1Hꢀimidazole (3b):44 White solid (261
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mg, 75%) mp (170ꢀ172° C); HNMR (CDCl3, 300 MHz): δ 7.73 (d, J = 8.1 Hz, 2H), 7.34 (d,
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4.16 (t, J = 9.9 Hz, 1H), 3.61ꢀ3.47 (m, 1H), 2.48 (s, 3H), 2.39 (s, 3H) ; 13 C NMR (CDCl3, 75
MHz): δ 156.8, 144.8, 140.1, 135.0, 133.3, 130.1, 128.7, 127.7, 127.1, 65.8, 55.3, 21.5, 16.7.
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4-(4-Fluorophenyl)-4, 5-dihydro-2-methyl-1-tosyl-1H-imidazole (3c):45 Colourless gum
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(242 mg, 73%); HNMR (CDCl3, 300 MHz): δ 7.74 (d, J = 8.1 Hz, 2H), 7.35 (d, J = 7.8 Hz,
2H), 7.01ꢀ6.89 (m, 4H), 4.96 (t, J = 8.1 Hz, 1H), 4.15 (t, J = 10.2 Hz, 1H), 3.58 (t, J = 8.1 Hz,
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1H), 2.46 (s, 3H), 2.39 (s, 3H); C NMR (CDCl3, 75 MHz): δ 162.2 (1JCF = 244.4 Hz),
156.6, 144.8, 137.4 (4JCF = 3.3 Hz), 135.0, 130.1, 128.0 (3JCF = 8.3 Hz), 127.1, 126.9, 115.5
(2JCF = 21.3 Hz), 65.8, 55.5, 21.5, 16.8.
4-(4-Bromophenyl)-4, 5-dihydro-2-methyl-1-tosyl-1H-imidazole (3d):31d Colourless gum
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(298 mg, 77%); HNMR (CDCl3, 300 MHz): δ 7.73 (d, J = 8.4 Hz, 2H), 7.44ꢀ7.30 (m, 4H),
6.92 (d, J = 8.4Hz, 2H), 4.95 (t, J = 8.7 Hz, 1H), 4.17 (t, J = 9.6Hz, 1H), 3.57 (t, J = 8.1 Hz,
1H), 2.46 (s, 3H), 2.40 (s, 3H).
(4R, 5R)-4, 5-Dihydro-2-methyl-4, 5-diphenyl-1-tosyl-1H-imidazole (3e):46 White sticky
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solid (296 mg, 76%); HNMR (CDCl3, 300 MHz): δ 7.53ꢀ7.42 (m, 2H), 7.39ꢀ7.31 (m, 3H),
7.29ꢀ7.19 (m, 6H), 7.12ꢀ6.99 (m, 1H), 6.96ꢀ6.83 (m, 2H), 4.99 – 4.84 (m, 2H), 2.53 (s, 3H),
2.42 (s, 3H) ; 13 C NMR (CDCl3, 75 MHz): δ 156.7, 144.5, 141.4 135.8, 129.7, 128.9, 128.7,
128.1, 127.7, 127.3, 126.5, 126.0, 77.1, 71.9, 21.5, 17.2.
3a, 4, 5, 6, 7, 7a-Hexahydro-2, 3a-dimethyl-1-tosyl-1H-benzo[d]imidazole (3f):32 Light
yellow gum (247 mg, 81%); 1HNMR (CDCl3, 300 MHz): δ 7.72 (d, J = 7.8 Hz, 2H), 7.33 (d,
J = 8.4 Hz, 2H), 3.61 (t, J = 6 Hz, 1H), 2.43 (s, 3H), 2.26 (s, 3H), 2.02ꢀ1.84 (m, 1H), 1.79ꢀ
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3a, 4, 5, 6, 7, 7aꢀHexahydroꢀ2ꢀmethylꢀ3aꢀphenylꢀ1ꢀtosylꢀ1Hꢀbenzo[d]imidazole (3g):32 Light
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yellow gum ( 282 mg, 77%); HNMR (CDCl3, 300 MHz): δ 7.36 (d, J = 8.4 Hz, 2H), 7.14ꢀ
7.08 (m, 3H), 7.08ꢀ6.96 (m, 4H), 4.24 (t, J = 5.4 Hz,1H), 2.40 (s, 3H), 2.31(s, 3H), 2.19ꢀ2.16
(m, 1H), 1.94ꢀ1.86 (m, 2H), 1.65ꢀ1.41 (m, 5H); 13 C NMR (CDCl3, 75 MHz): δ 155.9, 143.9,
135.8, 129.5, 128.0, 126.5, 124.8, 71.9, 66.9, 33.7, 28.0, 21.4, 18.4, 17.2, 16.8.
4ꢀEthylꢀ4, 5ꢀdihydroꢀ2, 4ꢀdimethylꢀ1ꢀtosylꢀ1Hꢀimidazole (3h):32 White solid (224 mg, 80%);
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mp (114ꢀ116 °C); HNMR (CDCl3, 300 MHz): δ 7.73 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.1
Hz, 2H), 3.53 (d, J = 9.3 Hz, 1H), 3.39 (d, J = 9.3 Hz, 1H), 2.45 (s, 3H), 2.30 (s, 3H), 1.52ꢀ
1.39 (m, 2H), 1.11 (s, 3H), 0.72 (t, J = 7.8 Hz, 3H); 13 C NMR (CDCl3, 75 MHz): δ 153.4,
144.5, 135.1, 128.9, 128.2, 67.4, 57.3, 33.5, 27.4, 22.5, 17.5, 8.8.
4, 5ꢀDihydroꢀ2, 4, 4, 5ꢀtetramethylꢀ1ꢀtosylꢀ1Hꢀimidazole (3i):32 White solid (221 mg, 79%),
mp (102 °Cꢀ104 °C); 1HNMR (CDCl3, 300 MHz): δ 7.70 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 7.8
Hz, 2H), 3.68 (q, J = 6.9 Hz, 1H), 2.41 (s, 3H), 2.25 (s, 3H), 1.28 (d, J = 6.6 Hz, 3H), 1.31 (s,
3H), 0.72 (s, 3H).
Nꢀ(2ꢀbromocyclohexyl)ꢀN'ꢀtosylacetamidine (3j):32 White solid (321 mg, 86%); mp (130ꢀ
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132° C); HNMR (CDCl3, 300 MHz): δ 7.84ꢀ7.77 (m, 2H), 7.29ꢀ7.23 (m, 2H), 6.24 (b, 1H),
4.19ꢀ4.05 (m, 1H), 3.94ꢀ3.78 (m, 1H), 2.40 (s, 3H), 2.33 (s, 3H), 2.23ꢀ2.14 (m, 2H), 1.84ꢀ
1.67 (m, 3H), 1.37ꢀ1.21 (m, 3H); 13 C NMR (CDCl3, 75 MHz): δ 165.5, 142.1, 140.4, 129.2,
126.4, 56.9, 53.8, 36.8, 32.1, 26.3, 23.9, 21.4, 21.2.
Nꢀ(2ꢀbromocyclooctyl)ꢀN'ꢀtosylacetamidine (3k):32 White solid (341 mg, 85%); mp (141ꢀ
142 °C); 1HNMR (CDCl3, 300 MHz): δ 7.79 (d, J = 7.8 Hz, 2H), 7.28ꢀ7.25 (m, 2H), 5.66 (d,
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J = 7.2 Hz, 1H), 4.44ꢀ4.32 ( m, 1H), 4.10ꢀ3.97 ( m, 1H), 2.41 ( s, 3H), 2.35 ( s, 3H), 2.23ꢀ
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2.08 ( m, 4H), 1.76ꢀ1.44 (m, 8H); C NMR (CDCl3, 75 MHz): δ 164.1, 142.2, 140.5, 129.2,
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Synthesis of diamine derivative (4a-4h)
To a solution of styrene (1 mmol) in CH3CN (8 mL) and H2O (1 mL), TsNBr2 (1.5 mmol)
was added in and the reaction was continued at room temperature (in case of cyclohexene, 80
°C) for almost 3 h. The excess solvent was removed in rotary evaporator and sodium
thiosulfate (200 mg approx.) was added followed by the addition of water (5 mL). The
reaction mixture was stirred for another 5 min and extracted with ethyl acetate followed by
dried over anhydrous sodium sulphate, and concentrated under reduced pressure. Further
purification of the crude product using petroleum ether/ethyl acetate as eluent led to isolation
of corresponding diamine derivative in pure form.
Nꢀ(1ꢀphenylꢀ2ꢀ(tosylamino)ethyl)acetamide (4a): White solid (282 mg, 85%); mp (110ꢀ115
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°C); HNMR (CDCl3, 300 MHz): δ 7.71 (d, J = 8.1 Hz, 2H), 7.42ꢀ 7.17 (m, 7H), 6.45 (d, J =
7.5 Hz, 1H), 5.14 (t, J = 6.3 Hz, 1H), 5.10ꢀ4.99 (m, 1H), 3.35ꢀ3.20 (m, 2H), 2.42 (s, 3H), 2.02
(s, 3H); 13C NMR (CDCl3, 75 MHz): δ 170.5, 143.7, 138.5, 136.6, 129.8, 128.9, 128.0, 126.9,
126.4, 52.7, 48.0, 23.2, 21.4; ESIꢀMS for (M+ Na)+ : 355.1092; found 355.23. Anal Calcd
(%) for C17H20N2O3S: C, 61.42; H, 6.06; N, 8.43; Found: C, 61.47; H, 6.13; N, 8.36.
Nꢀ(1ꢀ(4ꢀchlorophenyl)ꢀ2ꢀ(4ꢀmethylphenylsulfonamido)ethyl)acetamide (4b):White solid
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(312 mg, 85%); mp (122ꢀ124 °C); HNMR (DMSO, 300 MHz): δ 8.27 (d, J = 8.1Hz,
1H),7.70ꢀ7.66 (m, 1H), 7.59 (d, J = 7.8 Hz, 2H), 7.34(d, J = 8.1Hz, 4H), 7.23(d, J = 8.1Hz,
2H), 4.85 (t, J = 6.9 Hz, 1H), 2.91 (t, J = 6.6 Hz, 2H), 2.35 (s, 3H), 1.79 (s, 3H); 13C NMR
(DMSO, 125 MHz): δ 169.1, 143.1, 140.0, 137.6, 132.1, 129.9, 129.2, 128.5, 126.8, 52.1,
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47.5, 23.0, 21.3; HRMS (QTOFꢀESI+) calcd for C17H19ClN2O3S [M + H]+:367.0883; found
367.0817.
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Nꢀ(1ꢀ(4ꢀfluorophenyl)ꢀ2ꢀ(4ꢀmethylphenylsulfonamido)ethyl)acetamide (4c): White solid
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(287 mg, 82%); mp (138 ꢀ 140 °C); HNMR (DMSO, 300 MHz): δ 8.25 (d, J = 8.1Hz, 1H),
7.64ꢀ7.65 (m,1H),7.60 (d, J = 7.8 Hz, 2H),7.35(d, J = 7.5 Hz, 2H),7.30ꢀ7.21(m, 2H), 7.17ꢀ
7.06 (m, 2H), 4.87 (d, J = 7.2 Hz, 1H), 2.96ꢀ2.84 (m, 2H), 2.36 (s, 3H), 1.79 (s, 3H); 13C
NMR (DMSO, 100 MHz): δ 168.7, 142.7, 137.1 (4JCF = 35.5 Hz), 129.6, 128.9 (3JCF = 8.4
Hz), 126.5, 115.0 (2JCF = 21.2 Hz), 51.6, 47.4, 22.7, 21.0; HRMS (QTOFꢀESI+) calcd for
C17H19FN2O3S [M + H]+:351.1179; found 351.1179.
Nꢀ(1ꢀ(4ꢀbromophenyl)ꢀ2ꢀ(4ꢀmethylphenylsulfonamido)ethyl)acetamide (4d) : White solid
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(329 mg, 80%); mp (141ꢀ143 °C); HNMR (DMSO, 300 MHz): δ 8.27 (d, J = 8.4Hz, 1H),
7.677 (t, J = 6Hz, 1H), 7.59 (d, J = 8.1 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.34(d, J = 7.8 Hz,
2H), 7.17(d, J = 8.4 Hz, 2H), 4.82 (d, J = 7.8Hz, 1H), 2.91 (t, J = 6.3Hz, 2H), 2.36 (s, 3H),
1.79 (s, 3H); 13C NMR (DMSO, 125 MHz): δ 169.3, 143.1, 140.4, 137.5, 131.4, 129.9, 129.6,
126.8, 120.7, 52.2, 47.4, 23.0, 21.3; HRMS (QTOFꢀESI+) calcd for C17H19BrN2O3S [M +
H]+:411.0378; found 411.0367.
Nꢀ(2ꢀ(4ꢀmethylphenylsulfonamido)ꢀ1ꢀphenylpropyl)acetamide (4e): White solid (294 mg,
85%); mp (144ꢀ145 °C); 1HNMR(CDCl3, 300 MHz):δ 7.74 (d, J = 7.8 Hz, 2H), 7.34ꢀ7.23 (m,
6H), 6.49 (d, J = 7.5 Hz, 1H), 5.61 (d, J = 8.1 Hz, 1H), 4.78 (t, J = 8.1 Hz, 1H), 3.68ꢀ3.48 (m,
1H), 2.42 (s, 3H),1.95 (s, 3H), 0.914 (d, J = 6.9 Hz, 3H); 13CNMR(CDCl3,75MHz): δ 170.9,
143.3, 139.3, 138.2, 129.7, 128.9, 128.0, 127.2, 126.8, 58.8, 54.7,23.3,21.5,19.4; ESIꢀMS for
(M+ Na)+ : 369.1249; found 369.27; Anal Calcd (%) for C18H22N2O3S: C, 62.40; H, 6.40; N,
8.09; Found: C, 62.51; H, 6.49; N, 8.16.
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Nꢀ(2ꢀ(4ꢀmethylphenylsulfonamido)ꢀ1,2ꢀdiphenylethyl)acetamide (4f):5c White solid (318
mg, 78%); mp (158 ꢀ 160 °C); 1HNMR (CDCl3, 300 MHz): δ 7..46 (d, J = 8.4Hz, 2H), 7.33ꢀ
7.25 (m, 1H), 7.23ꢀ7.12 (m, 3H), 7.10 ꢀ 6.99 (m, 6H), 6.83 (d, J = 7.2 Hz, 2H), 6.50 ꢀ 6.39
(m, 1H), 5.19 (t, J = 10.2 Hz, 1H), 4.57 (t, J = 9.9 Hz, 1H), 2.31(s, 3H), 2.67(s, 3H); 13C
NMR (DMSO, 125 MHz): δ 169.1, 142.1, 140.3, 139.3, 138.7, 129.2, 128.1, 127.8, 127.5,
127.1, 126.9, 126.4, 62.5, 57.7, 23.0, 21.2; HRMS (QTOFꢀESI+) calcd for C23H25N2O3S [M
+ H]+:409.1586; found 409.1592
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Nꢀ(2ꢀ(tosylamino)cyclohexyl)acetamide (4g):47 White solid (254 mg, 82%); mp (158ꢀ160
°C); 1HNMR (CDCl3, 300 MHz): δ 7.77 (d, J = 8.1 Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H), 6.25 (d,
J = 7.8 Hz, 1H), 5.61 ( d, J = 8.1 Hz, 1H), 3.99ꢀ3.72 (m, 1H), 3.41 (d, J = 3.6 Hz, 1H), 2.41
(s, 3H), 1.90 (s, 3H), 1.73ꢀ1.54 (m, 2H), 1.51ꢀ1.25 (m, 6H); 13C NMR (CDCl3, 75 MHz): δ
170.1, 143.7, 136.9, 129.8, 127.1, 52.7, 49.4, 29.6, 27.5, 23.4, 23.3, 21.5, 19.9.
Nꢀ(2ꢀmethylꢀ3ꢀ(4ꢀmethylphenylsulfonamido)butanꢀ2ꢀyl)acetamide (4h) : (238 mg, 80%);
1HNMR (CDCl3, 300 MHz) 7.73 (d, J = 8.1Hz, 2H), 7.27ꢀ7.24 (m, 2H), 6.27 (d, J = 9 Hz,
1H), 5.74ꢀ5.70 (m, 1H), 3.36ꢀ3.30 (m, 1H), 2.39 (s, 3H), 1.90 (s, 3H), 1.26ꢀ1.19 (m, 6H),
0.89ꢀ0.87 (m, 3H); 13CNMR(CDCl3,75MHz):δ170.8, 143.0, 138.2, 129.6, 126.9, 57.0, 56.7,
24.4, 24.2, 24.1, 21.2, 16.5; HRMS (QTOFꢀESI+) calcd for C14H22N2O3S [M +
H]+:299.1429; found 299.1412.
General procedure for synthesis of diamines (5a-5c):
To a solution of olefin (1 mmol) and K2CO3 (5 mmol), in dry ethyl acetate (10 ml),
TsNBr2 (2.5 mmol) was added under nitrogen atmosphere. The reaction was stirred at
specific temperature (depending upon the type of substrate; RT for 1, 2ꢀdihydro pyran and
their derivatives and 60 °C in case of styrene) for appropriate time. Progress of the reaction
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was monitored by TLC. After completion of the reaction, an aqueous solution of 10% sodium
thiosulfate (10 mL) was added and the organic layer separated. The aqueous layer was
extracted with ethyl acetate, and the combined organic layer was washed with water and
finally with brine solution. Combined organic part was dried over anhydrous sodium sulfate
and concentrated. The crude product was purified by flash chromatography on silica gel
(230–400 mesh) with petroleum ether/ethyl acetate as eluent.
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1ꢀPhenylꢀN1, N2ꢀditosylethaneꢀ1, 2ꢀdiamine (5a):48 White sticky solid (310mg, 70%); H
NMR (CDCl3, 300 MHz): δ 7.82 (d, J = 8.1 Hz, 1H), 7.68 (d, J = 8.1 Hz, 2H), 7.59 (d, J =
7.8 Hz, 2H), 7.34ꢀ7.29 (m, 2H), 7.20ꢀ7.18 (m, 4H), 6.99ꢀ6.96 (m, 2H), 5.37 (bs, 1H), 4.82 (d,
J = 6 Hz, 1H), 4.33ꢀ4.27 (m, 1H), 3.22ꢀ3.15 (m, 2H), 2.43 (s, 3H), 2.39 (s, 3H); 13C NMR
(CDCl3, 75 MHz): δ 143.8, 143.6, 137.4, 136.6, 136.4, 129.8, 129.5, 128.9, 128.3, 127.2,
127.1, 126.5, 57.1, 48.2, 21.5; HRMS (QTOFꢀAPCI+) calcd for C22H25N2O4S2 [M + H] +:
445.1256; found 445.1243.
3, 4, 6ꢀTriꢀOꢀacetylꢀ1, 2ꢀdideoxyꢀ1, 2ꢀdiꢀ(pꢀtoluenesulfonamido)ꢀβꢀDꢀgalactopyranose
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(5b):34 White solid (464 mg, 74%); mp (110 ꢀ112 ºC); (1:1.25 diastereomeric mixture); H
NMR (CDCl3, 300 MHz, for major diastereomer): δ 7.85ꢀ7.70 (m, 4H), 7.34ꢀ7.29 (m, 4H),
6.39 (d, J = 9 Hz, 1 H), 5.31 (d, J = 6 Hz, 1H), 5.17ꢀ5.07 (m, 1H), 4.99ꢀ4.92 (m, 2 H), 4.16ꢀ
3.95 (m, 2H), 3.73ꢀ3.37 (m, 2H), 2.43(s, 3H), 2.42(s, 3H), 2.18 (s, 3H), 2.06ꢀ2.04 (m, 3H),
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1.98 (s, 3H); C NMR (CDCl3, 75 MHz): δ 172.0, 171.1, 170.6, 169.4, 143.7, 137.9, 137.5,
137.3, 137.0, 129.9, 129.6, 129.4, 127.3, 127.0, 83.5, 80.7, 72.8, 70.2, 68.1, 67.7, 67.4, 61.7,
60.7, 56.6, 54.5, 21.5, 20.7, 20.6, 20.0; HRMS (QTOFꢀESI+) calcd for C26H36N2O11S2 [M +
NH4 ] +: 630.1791; found 630.1774.
TetrahydroꢀN2,N3ꢀditosylꢀ2Hꢀpyranꢀ2,3ꢀdiamine (5c):34 White solid (284 mg, 67%); mp
(117ꢀ119 ºC); (1:1 diastereomeric mixture); 1H NMR (CDCl3, 300 MHz, for one
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diastereomer): δ 7.83ꢀ7.74 (m, 4H), 7.3ꢀ7.23 (m, 4H), 5.98 (d, J = 6 Hz, 1H), 5.46 (d, J = 9
Hz, 1H), 4.47 (t, J = 9 Hz, 1H), 3.73ꢀ3.61 (m, 1H), 3.38ꢀ3.35 (m, 1H), 2.97ꢀ2.95 (m, 1H),
2.41(s, 3H), 2.39 (s, 3H), 2.17ꢀ2.07 (m, 1H), 1.52ꢀ1.38 (m, 3H); 13C NMR (CDCl3, 75 MHz):
δ: 144, 143.8, 143.5, 143.4, 139.1, 138.4, 138.1, 137.3, 137.2, 129.9, 129.7, 129.5, 129.4,
127.1, 127, 126.4, 85, 82.1, 66.3, 65.2, 53.4, 53.0, 51.4, 30.4, 29.6, 27.6, 24.5, 21.5, 20.2;
HRMS (ESI) calcd for C19H24N2O5S2 [M +Na ] +: 447.1024; found 447.1022.
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ACKNOWLEDGMENT
Financial Support from the Department of Science and Technology (DST), India (Grant No.
SR/S1/OCꢀ43/2011) is gratefully acknowledged. IS thanks CSIR, India, SR thanks UGC, India and
LDC thanks DST, India, for research fellowships. We thank IITꢀGuwahati and NEHUꢀ
Shillong for analytical support.
1
Supporting Information: HꢀNMR, 13CꢀNMR spectra are available free of charge via the
Internet at http://pubs.acs.org
References
(1) (a) Li, G.; Kotti, S. R. S. S.; Timmons, C. Eur. J. Org. Chem. 2007, 2745ꢀ2758; (b) Cai,
Y.; Liu, X.; Li, J.; Chen, W.; Wang, W.; Lin, L.; Feng, X. Chem. Euro. J. 2011, 17, 14916 ꢀ
14921; (c) Luca, L. D. Curr. Med. Chem. 2006, 13, 1ꢀ23; (d) Berlinck, R. G. S.; Burtoloso,
A. C. B.; Kossuga, M. H. Nat. Prod. Rep. 2008, 25, 919ꢀ954.
(2) Tsujii, S.; Rinehart, K. L.; Gunasekera, S. P.; Kashman, Y.; Cross, S. S.; Lui, M. S.;
Pomponi, S. A.; Diaz, M. C. J. Org. Chem. 1988, 53, 5446ꢀ5453.
(3) Doores, K. J.; Mimura, Y.; Dwek, R. A.; Rudd, P. M.; Elliott, T.; Davis, B. G. Chem.
Commun. 2006, 1401ꢀ1403.
(4) Shibasaki, M.; Kanai, M. Eur. J. Org. Chem. 2008, 1839ꢀ1850.
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7
8
(5) (a) Lucet, D.; Le Gall, T.; Mioskowski, C. Angew. Chem. Int. Ed.1998, 37, 2580ꢀ2627;
(b) Nakayama, K.; Maruoka, K. J. Am. Chem. Soc. 2008, 130, 17666ꢀ17667; (c) Martins, J.
E. D.; Morris, D. J.; Wills, M. Tetrahedron Lett. 2009, 50, 688ꢀ692.
9
(6) (a) Kim, H. J.; Cho, S. H.; Chang, S. Org. Lett. 2012, 14, 1424ꢀ1427; (b) De Jong, S.;
Nosal, D. G.; Wardrop, D. J. Tetrahedron 2012, 68, 4067ꢀ4105; (c) Danneman, M. W.; Hong,
K. B.; Johnston, J. N. Org. Lett. 2015, 17, 2558ꢀ2561; (d) Olson, D. E.; Su, J. Y.; Roberts, D.
A.; Du Bois, J. J. Am. Chem. Soc. 2014, 136, 13506ꢀ13509; (e) Hong, K. B.; Johnston, J. N.
Org. Lett. 2014, 16, 3804ꢀ3807; (f) Chen, H.; Kaga, A.; Chiba, S. Org. Lett. 2014, 16, 6136ꢀ
6139; (g) Muniz, K. New J. Chem. 2005, 29, 1371ꢀ1385 (h) Muniz, K. Chem. Soc. Rev. 2004,
33, 166ꢀ174; (i) Chemler, S. R. Org. Biomol. Chem. 2009, 7, 3009ꢀ3019.
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51
52
53
54
55
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57
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(7) (a) Kharasch, M. S.; Priestley, H. M. J. Am. Chem. Soc. 1939, 61, 3425ꢀ3432; (b) Nair, C.
G. R.; Indrasen, P. Talanta 1976, 23, 239.
(8) (a) Saikia, I.; Borah, A. J.; Phukan, P. Chem. Rev. 2016, (DOI:
10.1021/acs.chemrev.5b00400); (b) Rajbongshi, K. K.; Borah, A. J.; Phukan, P. Synlett.
2016, (DOI: 10.1055/sꢀ0035ꢀ1562024); (c) Phukan, P.; Chakraborty, P.; Kataki, D. J. Org.
Chem. 2006, 71, 7533ꢀ7537; (d) Saikia, I.; Phukan, P. Tetrahedron Lett. 2009, 50, 5083ꢀ
5087; (e) Saikia, I.; Kashyap, B.; Phukan, P. Chem. Commun. 2011, 47, 2967ꢀ2969.
(9) Davies, S. G.; Polywka, M. E. C.; Thomas, S. E. Tetrahedron Lett. 1985, 26, 1461ꢀ1464.
(10) Tanuwidjaja, J.; Ng, S.ꢀS.; Jamison, T. F. J. Am. Chem. Soc. 2009, 131, 12084ꢀ12085.
(11) Bonney, K. J.; Braddock, D. C.; White, A. J. P.; Yaqoob, M. J. Org. Chem. 2010, 76,
97ꢀ104.
(12) Zhou, L.; Tan, C. K.; Zhou, J.; Yeung, Y.ꢀY. J. Am. Chem. Soc. 2010, 132, 10245ꢀ
10247.
(13) Lessard, J.; Driguez, H.; Vermes, J. P. Tetrahedron Lett. 1970, 11, 4887ꢀ4890
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