Synthesis and characterization of bromonium ylides and their unusual ligand transfer reactions with N-heterocycles

Article abstract of DOI:10.1021/ja063492+

Stable aliphatic bromonium ylides (R_fSO₂)₂C^--Br⁺C₆H₄-p-CF₃ (R_f = CF₃, CF₃(CF₂)₃) have been synthesized and struc

Full text of DOI:10.1021/ja063492+

Published on Web 07/11/2006
Synthesis and Characterization of Bromonium Ylides and Their Unusual
Ligand Transfer Reactions with N-Heterocycles
Masahito Ochiai,*,† Norihiro Tada,† Kentaro Murai,† Satoru Goto,† and Motoo Shiro‡
Faculty of Pharmaceutical Sciences, UniVersity of Tokushima, 1-78 Shomachi, Tokushima 770-8505, Japan, and
Rigaku Corporation, 3-9-12 Matsubara, Akishima, Tokyo 196-8666, Japan
Received May 19, 2006; E-mail: mochiai@ph.tokushima-u.ac.jp
Iodonium ylides, in which the ylide carbanions are stabilized by
two electron-withdrawing substituents, such as carbonyl or sulfonyl
groups, are readily accessible and have found many applications
in modern organic synthesis.1,2 In contrast to sulfonium and
phosphonium ylides, they serve as excellent progenitors for
generation of singlet carbenes (or carbenoids)3 because of the very
high leaving group ability of aryl-λ3-iodanyl groups4 and are
potential substitutes for explosive and toxic diazo compounds in
metal-carbenoid reactions.5 On the other hand, little is known
Figure 1. ORTEP drawing of 2a. Selected bond lengths (Å) and angles
(deg): Br(1)-C(1) 1.951(3), Br(1)-C(8) 1.868(3), S(1)-C(8) 1.704(4),
S(2)-C(8) 1.700(3), C(1)-Br(1)-C(8) 103.9(2), Br(1)-C(8)-S(1) 117.4-
(1), Br(1)-C(8)-S(2) 116.7(2), S(1)-C(8)-S(2) 125.4(2).
concerning the chemistry of the related group 17 bromonium ylides
because a method for their syntheses is not available.
In 1968, a transient formation of a highly labile bromonium ylide
was suggested by Koser in the reaction of a singlet carbene,
generated from 3,5-di-tert-butylbenzene 1,4-diazooxide by pho-
tolysis, with 2,6-diisopropyl-4-bromophenol.6 Stable aromatic
pseudo bromonium ylides, in which the ylide carbanions were
stabilized through delocalization to aromatic rings, have been
prepared by the thermolysis of diazodicyanoimidazole in bro-
mobenzenes;7 however, no stable and well-established aliphatic
bromonium ylides are known. We report herein, for the first time,
the synthesis, isolation, and characterization of stable aliphatic
bromonium ylides 2 whose structures were firmly established by
X-ray crystal analyses. Interestingly, the bromonium ylides 2
selectively undergo transfer of the aryl group to nitrogen hetero-
cycles, such as pyridines, yielding N-arylpyridinium salts.
Key to the success of the synthesis of 2 seems to be the presence
of two highly electron-withdrawing perfluoroalkylsulfonyl groups
(σp ) 0.96 for CF3SO2),10 which stabilize the ylide carbanions
through delocalization of the negative charge; thus, in contrast to
the highly acidic bissulfones 1 (pKa ) ca. -1 for 1a),8 less acidic
methylene compounds, such as PhSO2(CF3SO2)CH2 (pKa ) 5.1),
(CF3CO)2CH2 (pKa ) 5.3), (n-C3F7CO)2CH2, and dimedone (pKa
) 5.2), showed no evidences for formation of the stable bromonium
ylides under our conditions.
Solid state structure of 2a, obtained by recrystallization from
hexanes-ethyl acetate at -30 °C, illustrates a ylide structure (Figure
1): the four atoms Br1, C8, S1, and S2 are coplanar with the root
mean square deviation of 0.0359(2) Å from their least-squares
planes and with the sums of the C8-centered bond angles ∑°C8 )
359.5°, indicating an sp2 hybridization of the ylide carbanion C8.
The Br1-C8 distance of 1.868 Å is considerably shorter than that
of Br1-C1 bond (1.951 Å), but comparable to the reported vinylic
Csp2-Br(III) single bond (1.886 Å) of a vinyl-λ3-bromane.11 These
results suggest little double-bond character for the ylidic bond as
well as a negligibly small electrostatic attraction between the
oppositely charged Br1 and C8, probably because of a high
electronegativity of Br.12 The C1-Br1-C8 bond angle of 103.9°
is considerably greater than that (98.2°) for the bissulfonyl iodonium
ylide (CF3SO2)2C--I+Ph.13,14 This is probably due to the increased
nonbonded repulsions between the two organic substituents on Br-
(III) with a decreased atomic size. In addition to the intramolecular
short Br1‚‚‚O1 contact, a nearly linear C8-Br1‚‚‚O2* (x - 1/2,
-y - 1/2, z) secondary bonding to one of the sulfonyl oxygen atoms
of an adjacent molecule was found with a Br‚‚‚O distance of 2.987-
(2) Å, which links individual molecules of 2a into infinite zigzag
chains (Figure S1).15
Exposure of bis(trifluoromethylsulfonyl)methane (1a)8 to p-tri-
fluoromethylphenyl(difluoro)-λ3-bromane9 (1.1 equiv) in acetonitrile
at 0 °C for 3 h under argon resulted in the formation of
perfluoroalkylsulfonyl-substituted bromonium ylide 2a in 94% yield
(eq 1). Solid phase reaction (25 °C/5 min) without using a solvent
afforded a 67% yield of 2a. Reaction with bis(nonafluorosulfone)
1b (acetonitrile/0 °C/3 h) yielded the bromonium ylide 2b in 89%
yield. The ylide 2a is soluble in acetone, methanol, and ethyl acetate,
but not in the less polar solvents hexane and dichloromethane. These
ylides 2 are quite stable and can be stored indefinitely at room
temperature. Even in solution (acetone-d6), no decomposition of
2a was detected to a discernible extent when it was left standing
in the air at 23 °C for three months. The ylide 2a can be heated to
melting without any decomposition, but the continuous heating at
180 °C for 5 min resulted in the complete disappearance with
formation of p-(trifluoromethyl)bromobenzene.
Iodonium ylides undergo transylidations with various N, P, As,
S, and Se nucleophiles under thermal, catalytic, or photochemical
conditions;1 for instance, reaction of the iodonium bis(carboethoxy)-
methylide (EtO2C)2C--I+Ph with pyridine under heating produced
the pyridinium ylide (EtO2C)2C--N+C5H5 with reductive elimina-
tion of PhI.16 In a marked contrast, instead of transylidations, the
bromonium ylide 2 undergoes an arylation of N-heterocycles
† University of Tokushima.
‡ Rigaku Corporation.
9
9608
J. AM. CHEM. SOC. 2006, 128, 9608-9609
10.1021/ja063492+ CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Arylation of N-Heterocycles with Bromonium Ylide 2a
entry
2
N-heterocycle
time
3
yield (%)b
1
2
3
4
5
6
2a
2a
2a
2a
2a
2b
pyridine
3 days
24 h
3a
3b
3c
3d
3e
3f
77
81
54
(97)
(94)
84
4-tert-butylpyridine
4-(dimethylamino)pyridine
4,4′-bipyridine
N-methylimidazole
pyridine
2 hc
18 h
3 days
24 h
a Conditions: 1:2 2:N-heterocycle, dichloromethane, 45 °C, Ar. b Isolated
yields. Numbers in parentheses are 1H NMR yields. c Reaction was carried
out at room temperature.
Figure 2. Optimized structures of 2a and 5 with natural charges at Cylide
ipso, Br, and I calculated with the B3LYP/LanL2DZ method (Gaussian
03W).
,
C
Scheme 1
electronegativity of bromine relative to iodine.21 The remaining
positive charge in 2a is mostly delocalized on the aryl group (Figure
S3), which makes possible the facile SNAr reaction with N-
heterocycles.
Supporting Information Available: Experimental details, Scheme
S1, Figures S1-S3, and X-ray crystallographic data in CIF format for
2a and 3f. This material is available free of charge via the Internet at
http://pubs.acs.org.
selectively with concomitant reductive elimination of bissulfonyl-
bromomethanide anion (Table 1); thus, exposure of ylide 2a to
pyridine (2 equiv) in dichloromethane at 45 °C for 3 days under
argon afforded N-(p-trifluoromethylphenyl)pyridinium bissulfonyl-
bromomethanide 3a in 77% yield, with no evidences for transyli-
dations (entry 1).17,18 4,4′-Bipyridine and N-methylimidazole pro-
duced the pyridinium 3d and imidazolium salts 3e, respectively,
in high yields. Interestingly, this N-arylation of pyridine seems to
be specific for the bromonium ylides 2, and no formation of
pyridinium salt 3a was observed in the reaction with bissulfonyl
iodonium ylide (CF3SO2)2C--I+C6H4-p-CF3 5, which was recov-
ered unchanged under our conditions. Formation of these am-
monium salts 3 probably involves a rate-limiting nucleophilic attack
of N-heterocycles to the aromatic ipso carbons of 2, generating
Meisenheimer-type complexes, which in turn expel the bissul-
fonylbromomethanide anion as a leaving group. A greater electron-
withdrawing nature of λ3-bromanyl groups compared to that of λ3-
iodanyl groups seems to be responsible for these differences in
reactivity between the bromonium and iodonium ylides.19
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liberated selectively; thus, reaction of 2a with triethylamine (2
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produced the corresponding piperidinium methanide 4b quantita-
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