Direct transfer of the sulfonylimino group of imino-λ3- bromane to N-heterocycles and trialkylamines: Synthesis of N-iminoammonium ylides under metal-free conditions

Article abstract of DOI:10.1021/ol802383f

(Chemical Equation Presented) Exposure of N-heterocycles and aliphatic trialkylamines to trifluoromethanesulfonylimino-λ³-bromane at room temperature results in direct transfer of the sulfonylimino group to the nitrogen atoms and affords a vari

Full text of DOI:10.1021/ol802383f

ORGANIC
LETTERS
2009
Vol. 11, No. 2
281-284
Direct Transfer of the Sulfonylimino
Group of Imino-λ3-Bromane to
N-Heterocycles and Trialkylamines:
Synthesis of N-Iminoammonium Ylides
under Metal-Free Conditions
Masahito Ochiai,* Yufuko Kawano, Takao Kaneaki, Norihiro Tada, and
Kazunori Miyamoto
Graduate School of Pharmaceutical Sciences, UniVersity of Tokushima,
1-78 Shomachi, Tokushima 770-8505, Japan
mochiai@ph.tokushima-u.ac.jp
Received October 15, 2008
ABSTRACT
Exposure of N-heterocycles and aliphatic trialkylamines to trifluoromethanesulfonylimino-λ3-bromane at room temperature results in direct
transfer of the sulfonylimino group to the nitrogen atoms and affords a variety of iminoammonium ylides under transition-metal-free conditions.
The imino-λ3-bromane probably serves as an active nitrenoid species without any activation and produces the ammonium ylides via a bimolecular
nucleophilic substitution process.
Hypervalent sulfonylimino-λ3-iodanes PhIdNSO2Ar enable
a rich array of chemistry in modern organic synthesis.1 They
serve as excellent nitrenoid transfer agents either in the
aziridination of alkenes or in the amidation of alkanes via
C-H insertion using transition metal catalysts.2,3 These
reactions rely heavily on the hyper-leaving group ability of
aryl-λ3-iodanyl groups4 and on the generation of active metal-
nitrenoid species. Under thermal or catalytic conditions, they
transfer the sulfonylimino groups to a wide range of
heteroatom nucleophiles involving nitrogen heterocycles,
sulfides, sulfoxides, selenides, phosphines, and arsines.5-8
Thus, copper(II)-catalyzed reaction of PhIdNTs with excess
amounts of pyridines at room temperature afforded the
corresponding p-toluenesulfonyliminopyridinium ylides in
good yields.5a
In 2007, we reported the first synthesis of the related group
17 sulfonylimino-λ3-bromane 1, which involves a facile
ligand exchange of aryl(difluoro)-λ3-bromane on the bromi-
ne(III) with trifluoromethanesulfonamide (TfNH2) (Scheme
1).9 The sulfonylimino-λ3-bromane 1 functions as an efficient
sulfonylimino group donor and directly undergoes aziridi-
nation of olefins at ambient temperature stereospecifically
with retention of original stereochemistry. We report herein
(2) For aziridination of olefins, see: (a) Mansuy, D.; Mahy, J.-P.;
Dureault, A.; Bedi, G.; Battioni, P. J. Chem. Soc., Chem. Commun. 1984,
1161. (b) Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J. Am. Chem. Soc.
1994, 116, 2742. (c) Li, Z.; Quan, R. W.; Jacobsen, E. N. J. Am. Chem.
Soc. 1995, 117, 5889. (d) Au, S.-M.; Huang, J.-S.; Yu, W.-Y.; Fung, W.-
H.; Che, C.-M. J. Am. Chem. Soc. 1999, 121, 9120. (e) Dauban, P.; Saniere,
L.; Tarrade, A.; Dodd, R. H. J. Am. Chem. Soc. 2001, 123, 7707. (f)
Guthikonda, K.; Du Bois, J. J. Am. Chem. Soc. 2002, 124, 13672. (g) Cui,
Y.; He, C. J. Am. Chem. Soc. 2003, 125, 16202. (h) Leung, S. K.-Y.; Tsui,
W.-M.; Huang, J.-S.; Che, C.-M.; Liang, J.-L.; Zhu, N. J. Am. Chem. Soc.
2005, 127, 16629.
(1) Reviews: (a) Dauban, P.; Dodd, R. H. Synlett 2003, 1571. (b) Muller,
P.; Fruit, C. Chem. ReV. 2003, 103, 2905. (c) Zhdankin, V. V.; Stang, P. J.
Chem. ReV. 2002, 102, 2523. (d) Varvoglis, A. The Organic Chemistry of
Polycoordinated Iodine; VCH: New York, 1992. (e) HyperValent Iodine
Chemistry; Wirth, T., Ed.;Topics in Current Chemistry 224; Springer: Berlin,
2003. (f) Du Bois, J. Chemtracts 2005, 18, 1. (g) Zhdankin, V. V. Sci.
Synth. 2007, 31a (Chapter 31.4.1), 161
.
10.1021/ol802383f CCC: $40.75
Published on Web 12/16/2008
2009 American Chemical Society

p-CF3C6H4IdNSO2CF3 instead of 1 showed no evidence for
formation of the pyridinium ylide 2a under the conditions,
and a large amount of the hypervalent iminoiodane was
recovered unchanged. These results indicate greater reactivity
of the λ3-bromane 1 toward pyridine compared to that of
the imino-λ3-iodane (compare Table 1, entries 1 and 2).
Scheme 1
Table 1. Transylidation of Iminobromane 1 with
N-Heterocyclesa
a facile transfer of the sulfonylimino group of λ3-bromane 1
to the nitrogen atom of N-heterocycles and aliphatic trialky-
lamines, which affords sulfonyliminoammonium ylides in
excellent yields under metal-free, stoichiometric conditions
at room temperature.10
Exposure of equimolar pyridine to the sulfonyimino-λ3-
bromane 19 in acetonitrile at room temperature for 10 min
under argon resulted in the facile transimination between
Br(III) and N atoms, yielding N-triflyliminopyridinium ylide
2a11 quantitatively (Scheme 2). The transylidation probably
Scheme 2
involves the nucleophilic attack of pyridine to the ylidic
nitrogen anion of the bromane 1 with concomitant reductive
elimination of p-trifluoromethylphenyl bromide. It is noted
that use of the corresponding sulfonylimino-λ3-iodane
(3) For C-H insertion, see: (a) Breslow, R.; Gellman, S. H. J. Am. Chem.
Soc. 1983, 105, 6728. (b) Espino, C. G.; Wehn, P. M.; Chow, J.; Du Bois,
J. J. Am. Chem. Soc. 2001, 123, 6935. (c) Fructos, M. R.; Trofimenko, S.;
Diaz-Requejo, M. M.; Perez, P. J. J. Am. Chem. Soc. 2006, 128, 11784. (d)
Fiori, K. W.; Du Bois, J. J. Am. Chem. Soc. 2007, 129, 562. (e) Li, Z.;
Capretto, D. A.; Rahaman, R.; He, C. Angew. Chem., Int. Ed. 2007, 46,
5184. (f) Li, Z.; Capretto, D. A.; Rahaman, R.; He, C. J. Am. Chem. Soc.
2007, 129, 12058.
a Conditions: 1:1 N-heterocycle/bromane 1, room temperature, Ar.
b Isolated yields (1H NMR yield). c Iodane p-CF3C6H4IdNSO2CF3 was used.
d 2-Methylpyridine (2.5 equiv) was used. e At 0 °C.
(4) (a) Okuyama, T.; Takino, T.; Sueda, T.; Ochiai, M. J. Am. Chem.
Soc. 1995, 117, 3360. (b) Ochiai, M. In Chemistry of HyperValent
Compounds; Akiba, K.-y., Ed.; Wiley-VCH: New York, 1999; p 359.
(5) N-Heterocycles: (a) Jain, S. L.; Sharma, V. B.; Sain, B. Tetrahedron
Lett. 2003, 44, 4385. (b) He, L.; Chan, P. W. H.; Tsui, W.-M.; Yu, W.-Y.;
Che, C.-M. Org. Lett. 2004, 6, 2405.
Pyridines with a methyl group at the meta or para position
as well as 3,5-dimethylpyridine rapidly afforded N-trifly-
liminopyridinium ylides 2c-e in high yields under the metal-
free conditions, while transfer of the sulfonylimino group
to pyridines with electron-withdrawing p-chloro, p-bromo,
and p-cyano groups slows down (2-4 h). In the transylida-
tion of a sterically demanding pyridine with an o-methyl
group, excess amounts (2.5 equiv) of the substrate were used
to obtain a good yield (76%) of ylide 2b (Table 1, entries 3
and 4). 2,4,6-Trimethylpyridine afforded only a trace amount
of ylide 2f under our conditions (Table 1, entry 9). N-
Heterocycles such as quinoline, isoquinoline, and pyrazine
produced the N-iminoammonium ylides 2j-l smoothly.
Imination of 4,4′-bipyridyl with equimolar imino-λ3-
bromane 1 in acetonitrile gave a 72:28 mixture of monopy-
ridinium ylide 3a and bis(pyridinium ylide) 3b quantitatively;
however, use of excess amounts (3 equiv) of 4,4′-bipyridyl
afforded a 96% yield of the monoylide 3a selectively, and
(6) Sulfides and sulfoxides: (a) Okamura, H.; Bolm, C. Org. Lett. 2004,
6, 1305. (b) Mancheno, O. G.; Bolm, C. Org. Lett. 2006, 8, 2349. (c) Muller,
J. F. K.; Vogt, P. Tetrahedron Lett. 1998, 39, 4805. (d) Takada, H.;
Nishibayashi, Y.; Ohe, K.; Uemura, S. J. Org. Chem. 1997, 62, 6512. (e)
Leca, D.; Song, K.; Amatore, M.; Fensterbank, L.; Lacote, E.; Malacria,
M. Chem. Eur. J. 2004, 10, 906. (f) Nishibayashi, Y.; Chiba, T.; Ohe, K.;
Uemura, S. J. Chem. Soc., Chem. Commun. 1995, 1243.
(7) Phosphines Yamada, Y.; Yamamoto, T.; Okawara, M. Chem. Lett.
1975, 361.
(8) Arsines Ou, W.; Wang, Z.-G.; Chen, Z.-C. Synth. Commun. 1999,
29, 2301.
(9) Ochiai, M.; Kaneaki, T.; Tada, N.; Miyamoto, K.; Chuman, H.; Shiro,
M.; Hayashi, S.; Nakanishi, W. J. Am. Chem. Soc. 2007, 129, 12938.
(10) For reviews on N-heterocyclic ammonium ylides, see: (a) Tamura,
Y.; Ikeda, M. AdV. Heterocycl. Chem. 1981, 29, 71. (b) Timpe, H.-J. AdV.
Heterocycl. Chem. 1974, 17, 213.
(11) The pyridinium ylide 2a has been prepared by thermal reaction
(80 °C) of triflyl azide in pyridine in the presence of Cu catalyst in a
moderate yield (47%). See: Xu, Y.; Zhu, S. Tetrahedron 1999, 55, 13725.
282
Org. Lett., Vol. 11, No. 2, 2009

the bis-ylide 3b was produced predominantly by using 2.5
equiv of the iminobromane 1 (Scheme 3).
crystal analysis (Figure 2).13 The N1-N2 bond distances
(1.4228 Å for 2c and 1.4208 Å for 2k) are in a good
agreement with the mean value 1.401-1.454 Å reported for
Scheme 3
Changing a solvent from acetonitrile to dichloromethane
increases reactivity of the imino-λ3-bromane 1 toward
N-heterocycles and accelerates their iminations. Thus, the
reaction of 2-methylpyridine in dichloromethane afforded a
higher yield (79%) of the ylide 2b than that in acetonitrile
(Table 1, entries 3 and 5). To our delight, the ylide 2f with
two o-methyl groups was produced in 40% yield in dichlo-
romethane. Transylidation to weak nucleophiles such as
4-cyanopyridine and pyrazine was greatly improved in the
solvent, and more than 85% yields of the ylides 2i and 2l
were produced. It seems reasonable to assume that, in a
coordinating solvent such as acetonitrile, solvent coordination
to the positively charged bromine(III) atom of 1 probably
takes place and increases its stability. Experimental evidence
for the solvent coordination to the bromine(III) in acetonitrile
solution was obtained by the detailed analysis of the ESI
mass spectrum of the iminobromane 1, which revealed the
prominent ion peaks of [1·MeCN·Na]+ at m/z 435 and
[1·MeCN·H2O·Na]+ at m/z 453, in addition to the peaks of
the dimer (m/z 767) and the trimer (m/z 1138) (Figure 1).
Figure 2. ORTEP drawing of nitrogen ylides: (a) 2c and (b) 2k.
Selected bond lengths (Å) and angles (deg): N1-N2 1.4228(9),
S1-N2 1.5809(8), N1-N2-S1 112.65(5) for 2c; N1-N2 1.4208(13),
S1-N2 1.5776(11), N1-N2-S1 115.39(7) for 2k.
N-N single bonds,14 indicating little double-bond character
for the ylidic bonds.11,15
Direct transfer of the trifluoromethanesulfonylimino group
of the imino-λ3-bromane 1 to aliphatic trialkylamines pro-
ceeds smoothly even at 0 °C under metal-free conditions
and results in the formation of the corresponding ammonium
ylides 4 selectively in high yields. Thus, stoichiometric
reactions of N-methylpiperidine, quinuclidine, and 4-diazabi-
cyclo[2.2.2]octane (DABCO) with the bromane 1 in dichlo-
romethane at 0 °C afforded high yields (87%, 94%, and 89%)
of the iminoammonium ylides 4b-d, respectively (Table 2,
entries 2-4). Exposure of DABCO to 2.5 equiv of the
bromane 1 in dichloromethane produced the bis-ylide 4e
(87% yield) selectively.
Reaction mechanisms involving a unimolecular decom-
position of the imino-λ3-bromane 1 (path a: nitrene mech-
anism) and a bimolecular nucleophilic substitution on the
nitrogen atom (path b: nitrenoid mechanism) are shown in
Scheme 4. Nucleophilic pyridine probably coordinates to the
positively charged bromine(III) atom of the bromane 1 and
produces tricoordinated λ3-bromane 5 with a T-shaped
structure; however, this process does not seem to be
productive and the λ3-bromane 5 will be equilibrated with
the uncoordinated and/or solvent-coordinated imino-λ3-
bromane.16 Path a involves generation of highly reactive free
nitrene 6 via unimolecular decomposition of 1, because of
(12) Ochiai, M.; Suefuji, T.; Miyamoto, K.; Shiro, M. Org. Lett. 2005,
7, 2893.
Figure 1.
ESI mass spectrum of the imino-λ3-bromane 1 in MeCN
(5 × 10-3 M). Ar ) p-CF3C6H4.
(13) See Supporting Information, CCDC-705152 for 2c, and CCDC-
705153 for 2k.
(14) Allen, F. H.; Kennard, O.; Watson, D. G.; Brammer, L.; Orpen,
A. G.; Taylor, R. J. Chem. Soc., Perkin Trans. 2 1978, S1.
(15) For solid-state structures of iminoammonium ylides, see: (a) Legault,
C.; Charette, A. B. J. Am. Chem. Soc. 2003, 125, 6360. (b) Poe, R.; Schnapp,
K.; Young, M. J. T.; Grayzar, J.; Platz, M. S. J. Am. Chem. Soc. 1992,
114, 5054. (c) Morris, D. G.; Muir, K. W.; Chii, C. O. W. Polyhedron
2003, 22, 3345. (d) Cameron, A. F.; Duncanson, F. D.; Morris, D. G. Acta
Coordination of a solvent molecule will decrease the leaving
group ability of the aryl-λ3-bromanyl group,12 which in turn
decreases the reactivity of the imino-λ3-bromane 1 toward
N-heterocycles.
Crystallogr. 1976, B32, 1987
.
(16) As pointed out by one of the reviewers, ligand coupling pathway
on bromine(III) of the λ3-bromane 5, yielding directly the pyridinium ylide
2a, cannot be rigorously ruled out.
The molecular structures of the sulfonyliminoammonium
ylides 2c and 2k were determined unambiguously by X-ray
Org. Lett., Vol. 11, No. 2, 2009
283

It should be possible to distinguish between these two
processes by evaluating the time course for the formation of
the ylides 2. If generation of the nitrene 6 is involved (path a),
one might expect that the rate of pyridinium ylide formation
should be almost independent of pyridine concentration, while
that in a bimolecular concerted process path b seems to depend
on the concentration. Rate-determining attack of pyridine on
the free nitrene 6 seems to be unlikely. Figure 3 clearly indicates
Table 2. Transylidation of Iminobromane 1 with tert-Aminesa
a Conditions: 1:1 amine/bromane 1, CH2Cl2, 0 °C, 1 h, Ar. b Isolated
yields. c MeCN, room temperature. d Iminobromane 1 (2.5 equiv) was used.
Figure 3.
Time courses for transylidation between the imino-λ3-
bromane 1 (0.05 M) and 4-bromopyridine in MeCN-d3 at 23 °C
1
under argon: yields of the ylide 2h were determined by H NMR.
the hyper-leaving group ability of aryl-λ3-bromanyl groups.
Leaving group ability of aryl-λ3-bromanyl groups is greater
than that of aryl-λ3-iodanyl groups.17 Nucleophilic attack of
Concentration of 4-bromopyridine: (9) 0.25 M, (O) 0.1 M, (b)
0.05 M.
that transylidation between the imino-λ3-bromane 1 and 4-bro-
mopyridine at 23 °C does not involve the intermediacy of the
nitrene 6, since the rate of formation of the pyridinium ylide
2h in MeCN-d3 obviously depends on the concentration of the
pyridine.19 As a result, reaction of the bromane 1 with
4-bromopyridine seems to produce the ylide 2h via a concerted
SN2-type transition state such as 7. This mechanism well
explains the observed decrease in the rates of transylidation of
sterically demanding pyridines, shown in Table 1. A similar
concerted process is discussed in the aziridination of olefins
with the bromane 1.9
Scheme 4
In conclusion, direct transfer of the sulfonylimino group
of the imino-λ3-bromane 1 to the nitrogen atoms of N-
heterocycles and aliphatic trialkylamines provides a useful
tool for the synthesis of a variety of iminoammonium ylides
under metal-free conditions at ambient temperature. The
imino-λ3-bromane 1 probably acts as a reactive nitrenoid
species without any external activation and affords the ylides
via a bimolecular nucleophilic substitution process.
Acknowledgment. We gratefully acknowledge the Min-
istry of Education, Culture, Sports, Science, and Technology
of Japan for financial support in the form of a grant.
pyridine to the electron-deficient nitrene 6 with a highly
electron-withdrawing triflyl group (σp ) 0.96)18 produces
the pyridinium ylide 2a. Alternatively, in path b, nucleophilic
pyridine directly attacks the negatively charged nitrogen atom
of 1, because its σ* N-Br orbital is a low-lying LUMO.9
Here, the bromane 1 acts as a nitrenoid species and affords
2a via SN2 type transition state 7.
Supporting Information Available: Experimental details
and X-ray crystallographic data in CIF format for 2c and
2k. This material is available free of charge via the Internet
at http://pubs.acs.org.
OL802383F
(17) Ochiai, M.; Tada, N.; Okada, T.; Sota, A.; Miyamoto, K. J. Am.
Chem. Soc. 2008, 130, 2118.
(19) Addition of excess p-(trifluoromethyl)bromobenzene (0.5 M) did
not decrease the rate of formation of 2h to a discernible extent.
(18) Hansch, C.; Leo, A.; Taft, R. W. Chem. ReV. 1991, 91, 165.
284
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