Intramolecular homolytic aromatic substitution of alkyl 2-benzimidazolyl sulfones as a means of entry into alkyl radicals for organic synthesis

Article abstract of DOI:10.1016/j.tetlet.2008.02.174

The intramolecular radical aromatic substitution of heteroaryl sulfones by tethered aryl radicals has been investigated as a source of alkyl radicals. The 1-(2-iodobenzyl)benzimidazole-2-sulfonyl system was found to be the most effective, while a tetrazole-based system did not undergo the desired radical aromatic substitution at all. Application of the benzimidazole-based system to the generation of alkyl radical and their subsequent use in radical cyclizations was demonstrated.

Full text of DOI:10.1016/j.tetlet.2008.02.174

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 2999–3003
Intramolecular homolytic aromatic substitution of alkyl
2-benzimidazolyl sulfones as a means of entry into alkyl
radicals for organic synthesis
David Crich , Daniel Grant *
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607-7061, USA
Received 3 January 2008; revised 18 February 2008; accepted 29 February 2008
Available online 7 March 2008
Abstract
The intramolecular radical aromatic substitution of heteroaryl sulfones by tethered aryl radicals has been investigated as a source of
alkyl radicals. The 1-(2-iodobenzyl)benzimidazole-2-sulfonyl system was found to be the most effective, while a tetrazole-based system
did not undergo the desired radical aromatic substitution at all. Application of the benzimidazole-based system to the generation of alkyl
radical and their subsequent use in radical cyclizations was demonstrated.
Ó 2008 Elsevier Ltd. All rights reserved.
Ongoing projects in our laboratory required the use of
alkyl radical precursors beyond the halides, chalcogenides,
and thiocarbonyl derivatives traditionally employed.1,2
Nitroalkanes met many of our requirements1–3 but still suf-
fered from several limitations, most notably the high acid-
ity of the a-hydrogen. Looking for another group with
powerful electron-withdrawing properties but lower acidity
of the a-hydrogens, we focused our attention on the sulf-
ones. As this group is somewhat inert to direct displace-
ment by tributyltin hydride and its surrogates, and does
not take part in intramolecular homolytic substitution
reactions at sulfur1 we focused our attention on alkyl rad-
ical generation by intramolecular ipso-type substitution of
alkyl aryl sulfones.
The susceptibility of aryl sulfones toward ipso intra-
molecular homolytic substitution is well known.2 This reac-
tion typically involves attack of a C-centered radical upon
the ipso position of an aryl-sulfone, the cyclic radical
O
O
O
S
O
O
O
S
SH
I
S
R
O
RCH2X
[O]
R
R
Bu3Sn
R
S
+
I
O
6
5
3
1
2
4
RCH2
7
Scheme 1. General strategy for the generation of alkyl radicals from arylsulfones.
*
Corresponding author at present address. The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Tel.: +1 858 795 5237; fax: +1 858 646 3196.
E-mail address: dgrant@burnham.edu (D. Grant).
Present address: Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, MI 48202, USA.
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.02.174

3000
D. Crich, D. Grant / Tetrahedron Letters 49 (2008) 2999–3003
S
intermediate then fragments resulting in the formation of a
sulfonyl radical. The earliest example of this reaction
involved the attack of an alkyl radical on an aryl sulfon-
amide resulting in the transfer of the aryl group to the
alkane.2 Subsequently, this reaction has been widely
employed in the synthesis of novel fused hetero-cycles
and biaryls, with the focus on products derived from the
aryl moiety of the initial alkyl aryl sulfone.3–6 We envisaged
an alternative application of this chemistry with the
emphasis on the alkylsulfonyl radical expelled in the ipso-
substitution process as a precursor, via extrusion of sulfur
dioxide,7 as an alkyl radical progenitor.
The general strategy foreseen here (Scheme 1) involves
the synthesis of a system in which an aryl iodide trigger
is tethered to an aromatic thiol; this thiol 1 can then be
alkylated and subsequently oxidized to a sulfone 2. While
generally stable to typical synthetic manipulations this
sulfone 2 undergoes ipso-substitution upon generation of
the aryl radical 3 resulting in ejection of the alkyl sulfonyl
radical 6, which rapidly extrudes sulfur dioxide to leave the
desired alkyl radical 7.
C
N
Br
N3
NaN3
1) PPh3, THF
I
I
I
2) SCCl2, NaCO3H
2 steps 40%
DMF, 95 °C
quant.
14
15
16
NaN3
H2O
Δ
24%
H
N
ammonium
heptamolybdate
H2O2 30% in H2O
N
N
N
N
N
N
N
N
N
S
S
S O
O
2-(BrMe)Naph
Et3N, DMAP
N
N
EtOH, 0 °C
MeOH, rt
quant.
84%
I
I
I
17
19
18
Scheme 2. Synthesis tetrazole-based system 19.12
Table 2
Screening of arylsulfones for SHi
Arylsulfone
NMR Yield 2-
methylnaphthalene (%)
Other
products
9
0
Mixture of dehalogenated
and cyclized products
A series of sulfones were synthesized based on aromatic
thiols containing a second heteroatom for installation of
the 2-iodobenzyl ‘trigger’. The 2-methylnaphthalenyl radi-
cal was chosen as a model radical leaving group because
of the characteristic chemical shift of methyl singlet at d
2.48 in the product, which makes identification of a suc-
cessful reaction by NMR possible. Compounds 9, 11, and
13 (Table 1) were constructed by sequential alkylations of
the base compound followed by oxidation.8 A tetrazole-
based system 19 was constructed (Scheme 2) from the iso-
thiocyanate 16 by way of a [3+2] cycloaddition in aqueous
solution.9–11
N
SO2
N
Naph
11
13
19
10–20
Ph
20
4:1, 20:product
N
SO2
N
Naph
40–50
Ph
21
28%
Radical reactions were performed by syringe pump con-
trolled addition of an AIBN/tributyltin hydride solution to
N
N
N
N
SO2
Naph
0
Ph
22
88%
Table 1
Synthesis of arylsulfones for screening
Base
Yield 3-step synthesis9
Compound
a refluxing solution of the various alkyl aryl sulfones in
order to minimize the concentration of stannane in an
effort to reduce premature trapping of the aryl radical
(Table 2). Not surprisingly, inspection of the reaction mix-
SH
OH
Naph
77, 70, 85
SO2
O
8
1
I
ture of the 2-mercaptophenol-based system 9 by H NMR
9
spectroscopy did not show evidence of successful homolytic
aromatic substitution, as indicated by the absence of 2-
methylnaphthalene. Rather, a complex mixture of dehalo-
genated starting material and biaryl compounds, presum-
ably the result of addition of the aryl radical to solvent
and possibly the 3-position of the alkoxy benzene ring,
was produced. Subjecting 11 to the same conditions
resulted in simple dehalogenation of the majority of the
starting material. However, the formation of 2-methyl-
naphthalene in 10–20% yield gave some grounds for opti-
mism. The benzimidazole system 13 was the most
successful precursor producing moderate amounts of
product in the screening reaction.
N
N
H
N
SO2
Naph
S
N
H
86, 92, 98
I
10
11
N
N
H
N
SO2
Naph
S
N
H
33, 59, 51
I
12
13

D. Crich, D. Grant / Tetrahedron Letters 49 (2008) 2999–3003
3001
Table 3
Two aspects of the tetrazole-based system 19 make it
Generation and cyclization of alkyl radical 34 from sulfone 28
quite interesting in the context of aromatic homolytic sub-
stitution. First, this system is the most electron deficient of
the systems studied making it highly susceptible to nucleo-
philic aromatic substitution, as exemplified by its wide-
spread application in the Kocienski modification of the
Julia benzothiazole-based olefination.12 Secondly, the use
of the tetrazole ring eliminates the possibility of the initial
aryl radical being trapped via an intramolecular 1,5-hydro-
gen transfer13–15 a process, which could play a role in the
poor conversion of imidazole-based system 11. Unfortu-
nately, the propensity of this system toward nucleophilic
aromatic substitution does not extend to radical aromatic
substitution, and the only reaction observed with 19 was
its clean conversion to the dehalogenated starting material
22; there was no evidence for the formation of 2-methyl-
naphthalene in this reaction.
Propagating reagent
Solvent
Addition time (h)
Yield of 36 (%)
Bu3SnH
Bu3SnH
Bu3SnH
TTMSH
TTMSH
Toluene
Toluene
Benzene
Benzene
Benzene
3
5
8
36
44
35
30
A
Immediate
5
Starting material 28 was recovered unchanged from this reaction.
benzimidazole 23 was treated with base and alkylated with
2-iodobenzyl bromide 14. The resulting chlorobenzimida-
zole 24 was converted to thione 25 by nucleophilic displace-
ment of chloride 24 with KSAc.16 This synthesis of 25 was
practical and scalable for the efficient preparation of larger
quantities. For the purpose of this investigation, the chal-
lenge of the generation of a primary alkyl radical was cho-
sen. Introduction of 2517 into an alkyl compound from the
alkyl halide was completed in an efficient 2-step sequence
(Scheme 3).
Syringe pump controlled treatment of the alkyl arylsulf-
one 2818 in refluxing toluene with a solution of AIBN and
tributyltin hydride over 5 h (Scheme 4); resulted in success-
ful generation of the cyclized product 3619 in 44% yield
along with 28% of the dehalogenated starting material
30. Attempts to further suppress premature trapping of
the aryl radical by varying the addition time proved unsuc-
cessful (Table 3). Use of tris(trimethylsilyl) silane as a prop-
agating agent resulted in either complete dehalogenation of
the aryl iodide or failure of the reaction to propagate.
A second example involves a sulfonamide 37.20 Again,
the precursor 25 was incorporated smoothly into the alkyl
system, resulting in a yield of 92% over two steps (Scheme
5). The methyl-pyrrolidine 3921 product of the 5-exo-cycli-
zation of the alkyl radical was recovered in moderate yield
on treatment of 38 with tributyltin hydride.
Having established the supremacy of the benzimidazole
nucleus in the desired radical aromatic substitution a 1(2-
iodobenzyl)benzimidazole-2-thiol, which can be easily
incorporated into substrates as an alkyl radical precursor,
was synthesized. Thus, commercially available 2-chloro-
H
N
N
Cl
N
S
NaH, 14
KSAc
N
Cl
N
N
H
EtOH, Δ
THF, 0 °C
24
92%
I
25
I
23
74%
R
Cs2CO3
DMF, rt
R
Br
R
R
O
26
R = COOEt
N
N
R
R
ammonium
heptamolybdate
H2O2 30% in H2O
S
S
O
N
N
EtOH, 0 °C
In conclusion, a system has been designed which can be
effectively used as a precursor for alkyl radicals from sulf-
ones. The 2-thiobenzimidazole 25 can be incorporated into
an alkyl system in a facile 2-step sequence. The resulting
I
I
28
82% from 25
27
Scheme 3. Synthesis and incorporation of precursor 25.
R
R
R
R
N
N
N
N
N
Bu3Sn
S
O
O2S
S
O
N
O
R
R
N
O
32
N
I
R = COOEt
31
29
28
Bu3SnH
O
S
O
S
N
SO2
O
R
O
R
N
R
Bu3SnH
R
R
R
R
R
R
R
30
28%
36
44%
35
34
33
Scheme 4. Generation of alkyl radical 34 from sulfone 28.

3002
D. Crich, D. Grant / Tetrahedron Letters 49 (2008) 2999–3003
62.5, 98.5, 124.1, 124.7, 126.8, 127.1, 127.8, 128.1, 128.3, 128.65,
O
S
N
N
SO2Ph
128.74, 130.0, 130.2, 130.9, 133.1, 133.3, 138.4, 139.5, 140.4; Anal.
Calcd for C21H17IN2O2S: C, 51.65; H, 3.51. Found: C, 51.83; H, 3.61.
1-(2-Iodobenzyl)-2-(2-naphthylmethyl sulfonyl)benzimidazole (13) a
white solid. Mp 148–150 °C, 1H NMR (500 MHz, CDCl3): 4.99 (s,
2H), 5.05 (s, 2H), 5.92 (d, J = 8.0 Hz, 1H), 6.61 (t, J = 7.5 Hz, 1H),
6.78 (t, J = 7.5 Hz, 1H), 6.96 (d, J = 8.5 Hz, 1H), 7.25 (dd,J = 2.0,
8.0 Hz, 1H), 7.33 (dt, J = 1.0, 8.0 Hz, 1H), 7.41–7.48 (m, 2H), 7.51 (t,
J = 1.0, 7.5 Hz, 1H), 7.64 (d, J = 7.5 Hz, 1H), 7.70–7.74 (m, 3H), 7.82
(d, J = 8.0 Hz, 1H), 8.00–8.03 (m, 1H).
1) 25, Cs2CO3,
DMF, rt
Br
N
O
N
SO2Ph
2) ammonium
heptamolybdate
H2O2 30% in H2O
92% two steps
37
I
38
O
N
S
SO2Ph
N
N
O
+
Bu3SnH, AIBN
5 hr, addition
N
9. Orth, R. E. J. Pharm. Sci. 1963, 52, 909–910.
SO2Ph
toluene, Δ
10. Lieber, E.; Chao, T. S.; Rao, C. N. R. Can J. Chem. 1959, 37, 118–
119.
39
42%
40
26%
11. 1-(2-Iodobenzyl)-5-thiotetrazole (17). Sodium azide (325 mg, 5.0
mmol) and 16 (0.9 g, 3.3 mmol) were dissolved in water (10 mL)
and DMF (5 mL). The reaction mixture was heated to 100 °C for
24 h, at which point it was then acidified to pH 5 and extracted with
EtOAc (3 ꢀ 25 mL), the organic layer was washed with brine and
dried with Na2SO4. The solvent was removed in vacuo and the residue
was purified by silica gel column chromatography (eluent: 50% to neat
Scheme 5. Alkyl radical generation via sulfone 38.
sulfone can then be used to generate the corresponding
alkyl radical under typical AIBN/tributyltin hydride medi-
ated conditions.
1
EtOAc in hexanes) to afford 17 (250 mg, 0.79 mmol, 24%). H NMR
(500 MHz, CD3OD): 5.48 (s, 2H), 7.07 (dt, J = 1.5, 7.5 Hz, 1H), 7.71
(dd, J = 1.5, 7.5 Hz, 1H), 7.36 (dt, J = 1.5, 8.0 Hz, 1H), 7.93 (dd,
J = 1.5, 8.0 Hz, 1H); 13C NMR (125 MHz, CD3OD): 54.4, 99.6,
128.4, 128.9, 129.7, 136.8, 139.6, 145.0. 1-(2-Iodobenzyl)-5-(naph-
References and notes
1. Crich, D.; Hutton, T. K.; Ranganathan, K. J. Org. Chem. 2005, 70,
7672–7678.
2. Loven, R.; Speckamp, W. N. Tetrahedron Lett. 1972, 16, 1567–1570.
3. Caddick, S.; Aboutayab, K.; West, R. Synlett 1993, 231–232.
4. Caddick, S.; Aboutayab, K.; West, R. I. J. Chem. Soc., Chem.
Commun. 1995, 1353–1354.
5. Aldabbagh, F.; Bowman, W. R.; Mann, E. Tetrahedron Lett. 1997,
38, 7937–7940.
6. Aldabbagh, F.; Bowman, W. R. Tetrahedron 1999, 55, 4109–4122.
7. Chatgilialoglu, C.; Lunazzi, L.; Ingold, K. U. J. Org. Chem. 1983, 48,
3588–3589.
thylmethylthio)tetrazole (18). To
a solution of 17 (200 mg,
0.629 mmol), Et3N (135 lL, 0.950 mmol) and DMAP (5 mg) was
added 2-bromomethyl naphthalene (153 mg, 692 lmol). The reaction
mixture was kept stirring at rt for 3 h before the solvent was removed
in vacuo. The residue was partitioned between EtOAc and satd
NaHCO3 (25 mL each), the organic layer was then evaporated and
the residue was purified by silica gel column chromatography to
afford the title compound 18 (286 mg, 0.629 mmol, quant. yield) as a
1
colorless oil. H NMR (500 MHz, CDCl3): 4.67 (s, 2H), 5.31 (s, 2H),
6.62 (dd, J = 1.5, 7.5 Hz, 1H), 6.94 (dt, J = 1.5, 7.5 Hz, 1H), 7.09 (dt,
J = 1.5, 7.5 Hz, 1H), 7.43 (dd, J = 2.0, 8.0 Hz, 1H), 7.45–7.48 (m,
2H), 7.75–7.80 (m, 5H); 13C NMR (125 MHz, CDCl3): 38.4, 55.4,
97.9, 126.5, 126.6, 126.7, 127.7, 128.0, 128.3, 128.6, 128.8, 130.4,
132.9, 133.0, 133.2, 135.4, 139.8, 154.1; EI-HRMS calcd [M]+:
458.00621, found: 458.00710. 1-(2-Iodobenzyl)-5-(naphthylmethyl-
sulfonyl)tetrazole (19). Ammonium heptamolybdate (75 mg) and 18
(250 mg, 0.545 mmol) were taken up in EtOH (5 mL) and H2O2 (30%
in water, 1 mL) was added. The reaction mixture was kept stirring for
24 h before being filtered through a plug of silica (eluent: EtOAc),
evaporation of the solvent in vacuo afforded the title compound 19.
(225 mg, 0.46 mmol, 84%). 1H NMR (500 MHz, CDCl3): 5.00 (s, 2H),
5.36 (s, 2H), 6.26 (d, J = 7.5 Hz, 1H), 6.81 (t, J = 7.5 Hz, 1H), 6.88 (t,
J = 7.5 Hz, 1H), 7.33 (d, J = 8.0 Hz, 1H), 7.52–7.58 (m, 2H), 7.71–
7.85 (m, 5H); 13C NMR (125 MHz, CDCl3): 57.3, 62.8, 98.2, 122.2,
127.1, 127.6, 127.8, 128.3, 128.4. 128.6, 129.2, 130.4, 131.6, 133.1,
133.5, 135.0, 139.8, 152.2.
8. General synthesis of compounds 9, 11, and 13. To a solution of 2-thio
imidazole/phenol (2.0 mmol) and 2-(bromomethyl)naphthalene
(486 mg, 2.2 mmol) dissolved in DCM (10 mL) and CH3CN (5 mL)
were added Et3N (3.0 mmol) and DMAP (5 mg). The reaction
mixture was stirred 2 h at rt, the solvent was then removed in vacuo
and the residue was taken up in DCM (25 mL) and washed with water
(2 ꢀ 25 mL) the organic layer was concentrated in vacuo and the
residue was purified by silica gel column chromatography. A solution
of the resulting thioether (1.17 mmol) and 2-iodobenzyl bromide
(1.4 mmol) in DMF (10 mL) was treated with K2CO3 (1.75 mmol).
The reaction mixture was stirred at rt for 14 h before it was
partitioned between EtOAc (25 mL) and water (30 mL), the organic
layer was then washed with brine and dried with Na2SO4. The solvent
was removed in vacuo and the residue was purified by silica gel
chromatography. Oxidation of the resulting thioether (1.25 mmol)
was undertaken with catalytic ammonium heptamolybdate (154 mg,
10 mol %) in EtOH (5 mL). To this solution was added H2O2 (30% in
water, 2.0 mL); after stirring for 14 h the reaction mixture was
partitioned between water (20 mL) and EtOAc (20 mL), the organic
layer was evaporated and the residue was purified by silica gel column
chromatography. 2-[20-(2-Iodobenzyloxy)phenylsulfonylmethyl]naph-
thalene (9) as a white solid, mp 147–149 °C, 1H NMR (500 MHz,
CDCl3): 4.75 (s, 2H), 5.30 (s, 2H), 6.99 (t, J = 7.5 Hz, 1H), 7.27 (dd,
J = 1.5, 8.5 Hz, 1H), 7.43–7.47 (m, 2H), 7.51 (t, J = 8.0 Hz, 1H), 7.56
(dt, J = 1.5, 7.5 Hz, 1H), 7.63 (s, 1H), 7.69–7.78 (m, 4H), 7.89–7.92
(m, 2H); 13C NMR (125 MHz, CDCl3): 60.9, 75.2, 96.9, 113.6, 121.4,
125.5, 126.3, 126.5, 126.8, 127.7, 127.9, 128.3, 129.0, 129.2, 130.1,
130.6, 131.4, 133.1, 135.7, 137.9, 139.3, 156.2. 1-(2-Iodobenzyl)-2-
(naphthylmethylsulfonyl)imidazole (11) as a white solid 1H NMR
(500 MHz, CDCl3): 4.67 (s, 2H), 4.75 (s, 2H), 6.15 (s, 1H), 6.60 (s,
1H), 6.79 (s, 2H), 7.21–7.25 (m, 1H), 7.25 (s, 1H), 7.74–7.51 (m, 2H),
7.52 (s, 1H), 7.64–7.83 (m, 4H); 13C NMR (125 MHz, CDCl3): 55.4,
12. Blakemore, P. R.; Cole, W. J.; Kochienski, P. J.; Morley, A. Synlett
1998, 26–28.
13. Karady, S.; Abramson, N. L.; Dolling, U.-H.; Douglas, A. W.;
McManemin, G. J.; Marcune, B. J. Am. Chem. Soc. 1995, 117, 5425–
5426.
14. Karady, S.; Cummins, J. M.; Dannenberg, J. J.; del Rio, E.; Dormer,
P. G.; Marcune, B. F.; Reamer, R. A.; Sordo, T. L. Org. Lett. 2003, 5,
1175–1178.
15. Cummins, J. M.; Dolling, U.-H.; Douglas, A. W.; Karady, S.;
Leonard, W. R.; Marcune, B. F. Tetrahedron Lett. 1999, 40, 6153–
6156.
16. Allin, S. M.; Bowman, W. R.; Karim, R.; Rahman, S. S. Tetrahedron
2006, 62, 4306–4316.
17. 1-(2-Iodobenzyl)-2-thiobenzimidazole (25). Compound 24 (3.4 g,
9.2 mmol) was dissolved in EtOH (30 mL) and THF (10 mL), to this
solution was added KSAc (1.27 g, 11.1 mmol). The reaction mixture
was heated to 70 °C and stirred for 24 h, at which point TLC

D. Crich, D. Grant / Tetrahedron Letters 49 (2008) 2999–3003
3003
confirmed consumption of 24. The solvent was then removed in vacuo
and the residue was taken up in water (50 mL) and extracted with
EtOAc (3 ꢀ 50 mL), the organic layer was then washed with brine and
concentrated. The residue was initially subjected to silica gel column
chromatography (eluent: 20% EtOAc in hexanes). However, recrys-
tallization from a solution of 15% EtOAc in hexanes was needed for
complete purification of the title product and afforded 25 (2.5 g,
6.8 mmol, 74%) as a white fluffy solid. Mp 220–222 °C, 1H NMR
(500 MHz, CD3OD): 5.51 (s, J = 2H), 6.71 (d, J = 8.0 Hz, 1H), 6.90
(d, J = 8.0 Hz, 1H), 6.95 (dt, J = 1.5, 8.0 Hz, 1H), 7.10 (dt, J = 1.5,
8.0 Hz, 1H), 7.15–7.20 (m, 2H), 7.25 (d, J = 7.5 Hz, 1H), 7.87 (dd,
J = 1.5, 7.5 Hz, 1H); 13C NMR (125 MHz, CD3OD): 52.4, 97.1,
109.8, 110.1, 122.9, 123.6, 127.1, 128.5, 129.2, 131.1, 132.5, 137.1,
139.5, 169.2.
the residue was purified by silica gel column chromatography (eluent:
10% EtOAc in hexanes) to afford 28 (409 mg, 0.655 mmol, 82%) as a
1
crystalline solid. Mp 96–99 °C, H NMR (500 MHz, CDCl3): 1.25 (t,
J = 7.0 Hz, 6H), 2.43–2.46 (m, 2H), 2.66 (d, J = 7.5 Hz, 2H), 3.69–
3.73 (m, 2H), 4.18–4.22 (m, 4H), 5.11 (d, J = 10.0 Hz, 1H), 5.14 (dd,
J = 1.5, 17.0 Hz, 1H), 5.60–5.70 (m, 1H), 5.81 (s, 2H), 6.49 (d,
J = 7.5 Hz, 1H), 6.97 (t, J = 7.5 Hz, 1H), 7.15–7.20 (m, 2H), 7.36–
7.39 (m, 2H), 7.86–7.90 (m, 2H); 13C NMR (125 MHz, CDCl3): 14.1,
25.5, 37.7, 50.9, 53.9, 56.2, 61.9, 96.9, 11.5, 120.2, 121.9, 124.4, 126.4,
126.7, 128.9, 129.7, 131.3, 135.4, 137.2, 139.7, 141.1, 147.3; ESI-
HRMS calcd [M+H]+: 625.08693, found: 625.0852.
19. Kim, S.; Jon, S. Y. J. Chem. Soc., Chem. Commun. 1998, 815–
816.
20. N-Allyl-N-[2-(2-iodobenzyl)-1-benzimidazoylethylsulfonyl]-N-phenyl-
1
18. 4,4-Bis(ethoxycarbonyl)-6-[1-(2-iodobenzyl)-2-benzimidazolesulfonyl]-
1-hexene (28). A solution of 25 (298 mg, 0.8 mmol) and 26 (250 mg,
0.8 mmol) in DMF (10 mL) was treated with Cs2CO3 (390 mg,
1.2 mmol) and stirred for 12 h at rt. The reaction mixture was poured
into water (50 mL) and extracted with EtOAc (3 ꢀ 25 mL) the organic
layer was then washed with brine and evaporated affording thioether
27. The crude thioether was taken up in THF and EtOH (5 mL each),
to this solution was added a suspension of ammonium heptamolyb-
date (50 mg, 40 lmol) in H2O2 (30% in water, 2.5 mL). The reaction
was kept stirring for 24 h before being poured into water (50 mL) and
extracted with EtOAc (3 ꢀ 25 mL), the organic layer was washed with
brine and dried with Na2SO4. The solvent was then evaporated and
sulfonamide (29). A colorless oil. H NMR (500 MHz, CDCl3): 3.72–
3.75 (m, 2 H), 3.85 (d, J = 6.5 Hz, 2H), 3.90–3.93 (m, 2H), 5.17 (dd,
J = 1.5, 21.5 Hz, 1H), 5.20 (dd, J = 1.5, 28.5 Hz, 1H), 5.60–5.68 (m,
1H), 5.79 (s, 2H), 6.48 (dd, J = 1.0, 7.5 Hz, 1H), 6.98 (dt, J = 1.0,
7.5 Hz, 1H), 7.21 (dd, J = 1.5, 7.0 Hz, 1H), 7.37–7.44 (m, 2H), 7.50 (t,
J = 8.0 Hz, 2H), 7.59 (t, J = 8.0 Hz, 1H), 7.79 (dd, J = 1.0, 8.0 Hz,
2H), 7.90 (d, J = 8.0 Hz, 2H); 13C NMR (125 MHz, CDCl3):
41.4, 52.0, 53.9, 54.3, 96.9, 111.6, 120.6, 121.8, 124.6, 126.7, 127.3,
129.0, 129.4, 129.8, 132.1, 133.1, 135.5, 137.1, 138.6, 139.7, 140.9,
147.2.
21. Padwa, A.; Nimmesgern, H.; Wong, G. S. K. J. Org. Chem. 1985, 50,
5620–5627.