Direct nucleophilic addition versus a single-electron transfer pathway of σH adduct formation in vicarious nucleophilic substitution of hydrogen

Article abstract of DOI:10.1002/ejoc.200400034

Two mechanistic pathways of formation of σ^H adducts, which are key intermediates in the vicarious nucleophilic substitution of hydrogen, namely direct nucleophilic addition of carbanions to nitroarenes and a two-step mechanism involving an electron-transfer process, are discussed on the basis of the existing data and results of the VNS reactions in which a radical probe - chloromethyl aryl sulfone bearing a 2,2-dimethylcyclopropyl substituent - was used as the carbanion precursor. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200400034

FULL PAPER
Direct Nucleophilic Addition versus a Single-Electron Transfer Pathway of σH
Adduct Formation in Vicarious Nucleophilic Substitution of Hydrogen
Mieczysław Makosza*[a] and Andrzej Kwast[a]
˛
Keywords: Carbanions / Nucleophilic addition / Nucleophilic substitution / Electron transfer
Two mechanistic pathways of formation of σH adducts, which
are key intermediates in the vicarious nucleophilic substitu-
radical probe — chloromethyl aryl sulfone bearing a 2,2-di-
methylcyclopropyl substituent — was used as the carbanion
tion of hydrogen, namely direct nucleophilic addition of car- precursor.
banions to nitroarenes and a two-step mechanism involving
an electron-transfer process, are discussed on the basis of the
existing data and results of the VNS reactions in which a
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
detailed semi-quantitative studies have disclosed an effect
of base concentration on the rate of β-elimination and the
relative rates of the addition and elimination steps.[18] Much
less attention has been paid to the question of how the σH
adducts are formed. Formation of the anionic σ adducts of
carbanions to nitroarenes is a common initial step for the
VNS reaction, the SNAr reaction of halogens or other
leaving groups in nitroaromatic rings and some other
processes.[20Ϫ22] In general, two pathways are considered for
this process: direct nucleophilic addition and a two-step
process initiated by single-electron transfer (SET), resulting
in the formation of radicals and anion radicals, followed by
coupling of these paramagnetic species. The latter pathway
was recently often favoured for the formation of σX
adducts, which are intermediates in the SNAr of
halogens.[23Ϫ26] It appears, however, that the occurrence of
this pathway has been overestimated and the concept often
abused.[27] The possible intervention of a radical intermedi-
ate in the fluoride-promoted addition of silyl enol ethers
to nitroarenes resulting in σH adduct formation has been
investigated by RajanBabu et al.[28] They found that the re-
action with p-nitrocumyl chloride or 4-(cyclopropyl)nitro-
benzene gave normal products, and those expected from the
radical-ion intermediates were not observed.
In this paper we attempt to clarify whether the anionic
σH adducts of carbanions and nitroarenes — intermediates
in the VNS reaction — are formed by direct addition or by
a two-step process involving SET.
When analysing this problem, it should be taken into ac-
count that formation of the σH adducts by addition of car-
banions to nitroarenes is a reversible process. A frequently
observed influence of the reaction conditions, particularly
the strength and concentration of a base on the orientation
of VNS, as well as on its rate, estimated on the basis of a
competition between VNS and the substitution of halogens,
can only be explained by assuming the reversibility of the
Vicarious Nucleophilic Substitution of hydrogen (VNS)
is presently a well-established, general method for the intro-
duction of substituents into electron-deficient aromatic
rings, particularly those containing nitro groups.[1Ϫ4] The
reaction is general with respect to the electron-deficient ar-
enes and nucleophiles used, and practically all carbo- and
heterocyclic nitroarenes undergo this reaction provided
there are hydrogen atoms in the positions ortho or para to
the nitro group. On the other hand, carbanions containing
leaving groups such as halogens, ArO, RO, ArS, etc. can
undergo this reaction, without limitations, provided they
are sufficiently stable and active nucleophiles. Besides car-
banions, anions of alkyl hydroperoxides[5Ϫ8] — tert-butyl
and cumyl in particular — and a plethora of aminating ag-
ents such as derivatives of hydrazine,[9,10] hydroxylam-
ine[11,12] and sulfenamide[13,14] undergo the VNS, introduc-
ing OH and NH2 or NHR substituents, respectively, into
nitroaromatic rings.
In spite of such a large field of applications the mechan-
istic features of this process are not well known and are
essentially based on qualitative studies and observations.
Since the VNS reaction is a multistep process embracing
formation of the σH adducts and their transformation into
products, a few mechanistic questions should be addressed,
the most important concerning the formation of the σH in-
termediate adducts and how they are transformed into the
products. The second point has been discussed in a few
mechanistic papers and there is no doubt that the trans-
formation of the σH adducts into the products proceeds as
a base-induced β-elimination of HX.[15Ϫ19] Recently, more
[a]
Institute of Organic Chemistry, Polish Academy of Sciences,
Kasprzaka 44, 01Ϫ224 Warsaw, Poland
Fax: (internat.) ϩ48-22-6326681
E-mail: icho-s@icho.edu.pl
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DOI: 10.1002/ejoc.200400034
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M. Ma¸kosza, A. Kwast
FULL PAPER
σH adduct formation.[15Ϫ19,29] The addition of various nu-
The differences between the orientation of the addition
cleophiles to more electrophilic polynitroarenes was also of the Grignard reagents and halocarbanions in the VNS
found to be a reversible process and in many cases corre- reaction suggest strongly that in the latter case formation
sponding thermodynamic data were obtained.[30,31]
of the new CϪC bond in the addition is an ionic process.
A general scheme for alternative pathways of the VNS
The participation of radical intermediates in a formally
with a model α-chloroalkyl phenyl sulfone carbanion with polar reaction can be detected when the starting materials
nitrobenzene derivatives is presented in Scheme 1.
contain fragments able to enter rapid free-radical reactions.
These compounds are considered as radical probes or so-
called radical clocks.[37] When free radicals are real inter-
mediates in the process the course of the reaction and the
nature of the final products should change with the use of
such substrates. Thus, in our attempts to clarify whether the
intermediate σH adducts are formed by a two-step process
including SET, we used aryl α-chloroalkyl sulfones, which
can behave as radical clocks.
Results and Discussion
Scheme 1
According to the microreoversibility principle, formation
The most common and widely used radical probes are
of the σH adduct by a two-step SET mechanism requires those possessing a 4-pentenyl chain attached to the carbon
that its dissociation should also occur by homolytic CϪC atom that is the potential radical centre.[36,37] When formed
bond cleavage, producing the nitroarene anion-radical the 5-hexenyl radicals undergo cyclization, giving products
Ϫ
ArNO2 and a free radical of the chlorosulfone. The latter different from those expected for processes that do not in-
is poorly stabilized,[32] so this dissociation pathway seems volve free radicals. Although intramolecular addition of the
unlikely as an alternative to the ionic process. Moreover, carbon radical to the terminal double bond is not a very
this dissociation should be followed by a single-electron fast reaction — its rate determined for unsubstituted and
transfer from the nitroarene radical anion to the sulfone- alkyl-substituted 5-hexenyl radicals is around 105 sϪ1
—
free radical, so the starting reactants are recovered. Thus, there are numerous examples of the successful application
reversibility of the σH adduct formation suggests that they of this class of radical probes. However, radicals stabilized
are formed rather by direct addition (Scheme 1, path a).
with a sulfonyl group, when generated by tin hydride re-
Additional arguments against SET as a step in the forma- duction of the appropriate α-halosulfone, do not cyclize ef-
tion of the σH adducts came from the observation that the ficiently,[38] whereas the corresponding α-chloro-α-sulfonyl
ratio of o- and p-substitution in nitrobenzene and its deriva- radicals, which are of interest to us, have not yet been stud-
tives is strongly affected by the reaction conditions, particu- ied. In our hands the reaction of tributyltin hydride with
larly the base-solvent system. While reactions of chlorome- 1,1-dichloro-5-hexenyl phenyl sulfone did not provide re-
thyl aryl sulfone carbanion promoted by NaOH, tBuOK liable data concerning the rate of cyclization of such rad-
etc. in DMSO, DMF or liquid ammonia give o- and p- icals.
nitrobenzyl sulfones in ratios ranging from 1:2 to 2:1, de-
Nevertheless, the VNS reaction of chlorosulfone 1a was
pending on the kind of base and its concentration,[1Ϫ4,15,16] examined and the results have been included in this work.
substitution in the presence of tBuOK in a less-polar sol- However, for the above-mentioned reasons we turned to an-
vent (THF) often proceeds selectively ortho to the nitro other type of α-chlorosulfone-derived radical probe, namely
group.[15,33] It was assumed that the interaction of potass- chloro(2,2-dimethylcyclopropyl)methyl phenyl sulfone (1b).
ium cations of the tight ion-pairs existing in THF with the It is well-known that the rearrangement of cyclopro-
oxygen atoms of the nitro group attracts the ion pair, lead- pylmethyl radicals into homoallylic radicals by opening of
ing to the ortho addition of the carbanion to the nitroaro- the cyclopropane ring is one of the fastest known processes
matic ring. Addition of 18-crown-6 to the reaction medium among alkyl-radical transformations.[36,37,39,40] We have
eliminates this effect as it binds the Kϩ cations efficiently.
previously used an analogous compound for studies of the
According to Bartoli,[34] addition of MeMgBr or halophilic reaction, the halogen exchange between car-
EtMgBr to nitroarenes in THF gives the respective σH ad- banions and dimerization of carbanions.[41] In those studies
ducts ortho and para to the nitro group in ratios close to we found that the ring-opening reaction of chloro(2,2-di-
statistical in spite of the partially covalent character of methylcyclopropyl)methyl tolyl sulfone radical, generated
CϪMg bonding and the expected efficient interactions be- by Bu3SnH/AIBN reduction of the corresponding dichloro
tween the magnesium cation and oxygen atoms of the nitro derivative, proceeds with a very high rate constant (approx.
group. The absence of such an effect is apparently due to 109 sϪ1). A radical probe of a similar structure — cyclopro-
the mechanism of addition, which, as shown by Bartoli, pylmethyl phenyl sulfone — was later used by Chanon in
proceeds by SET, hence polar effects are negligible in the studies on radical intermediates in reactions of α-sulfonyl
σH adduct formation.[35]
carbanions with polyhalomethanes.[42] However, the rate
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Direct Nucleophilic Addition versus Single Electron Transfer
FULL PAPER
constant of the free-radical rearrangement of this cyclopro- products of the VNS reaction proceeding by β-elimination
pylmethyl derivative was estimated to be 107 sϪ1
.
of toluenesulfinic acid rather than HCl from the intermedi-
To clarify whether radical species participate in the for- ate σH adducts. The unexpected formation of products of
mation of σH adducts, selected α-chlorosulfones 1a and 1b, this type in VNS reactions will be presented and discussed
which could play the role of the radical probes, were sub- elsewhere.
mitted to the reaction with 2-chloronitrobenzene (2). The
The data collected in Table 1 show that starting materials
reactions of their structural analogues, 1-chlorohexyl tolyl that are able enter fast reactions via free radicals (radical
sulfone (1c) and 1-chloro-3-methylbutyl phenyl sulfone (1d) clocks) react with nitroarenes along the VNS reaction co-
with the same nitroarene were used as reference processes urse without the formation of side products. Particularly
(Scheme 2). The reactions were carried out under various diagnostic are experiments with 1b, which is a very fast rad-
conditions typical for the VNS reaction. Yields of the VNS ical clock.
products and observed side products were compared. The
results of these studies are summarised in Table 1.
Chlorosulfone 1b, which differs from 1d only by the type
of alkyl substituent, was expected to behave very similarly
to 1d, provided the formation of the σH adduct is a one-
step, ionic process. On the other hand, if the reaction pro-
ceeds by initial formation of the radical intermediate, it
should, at least partially, undergo a ring-opening process,
with formation of the tertiary alkyl radical (Scheme 3). The
latter, being nucleophilic in character, is expected to exhibit
lower reactivity towards the nitroarene radical-anion, and
therefore other reactions, for example hydrogen abstraction
from the solvent or from another source, rather than ad-
dition to the nitroarene, are more plausible. However, the
open-chain chlorosulfone 5 was not found in the reaction
mixture (by comparison with an authentic sample). More-
over, the σH adduct formed by addition of the rearranged
free radical to the nitroarene radical anion would be unable
to eliminate the HCl molecule by a base-induced β-elimin-
ation process. Conversion of such σH adducts into stable
products could eventually proceed by an oxidative pathway
giving products of different structure than 3b.
Scheme 2
Table 1. Reactions of chloroalkyl phenyl sulfones 1aϪd with 2-
chloronitrobenzene as in Scheme 2
[a]
[b]
4-Chloronitrobenzene (1 equiv.) was added. Not detected.
The reference sulfones 1c and 1d react with 2-chloronitro-
benzene (2) according to the VNS scheme giving products
3c and 3d, respectively, with good yields. Similar results
were also obtained for radical clocks 1a and 1b. In fact,
in all reactions of the chlorosulfones used, unidentified by-
products were detected only in very small amounts (Ͻ 1%
each). The only identified side products formed in note-
worthy amounts were nitrobenzylic chlorides 4, and some-
Scheme 3
It seems clear that participation of an electron transfer in
times also products of their transformations into the corre- the σH adduct formation step should change the reaction
sponding nitrophenones. These compounds are apparently course considerably, preventing the VNS process to a sub-
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M. Ma¸kosza, A. Kwast
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chloromethyl aryl sulfones with appropriate alkyl bromides under
PTC conditions according to the procedure described earlier for an
analogous alkylation.[44]
stantial degree. Similar considerations can also be made for
the possible SET reaction pathways in the reaction of 1a.
Reactions carried out at room temperature in the KOH/
DMSO system in which the only operating bases, soluble
in the reaction medium, are the chlorosulfone carbanions,
seem to be particularly diagnostic. Due to a relatively low
rate of β-elimination of HCl from the σH adducts promoted
by this weak base, these conditions favour equilibration of
the addition process. The concentration of σH adducts is
therefore relatively high, and reversibility of their formation
gives the biggest chance for possible electron transfer and
further, irreversible radical processes to occur. In fact, un-
der these conditions 1b reacts even more readily than 1d.
An additional argument against the SET pathway for the
VNS reaction came from the experiment in which 1b was
treated with 2 and 4-chloronitrobenzene in equimolar
amounts. The latter nitroarene has a similar electron affin-
ity to that of 2, as can be seen from their reduction poten-
tials,[43] while its reactivity in the VNS reactions with ter-
tiary carbanions of α-chlorosulfones is very low in the
KOH/DMSO system.[1Ϫ4] The results in Table 1 (Entry 3)
show that this additive does not affect the VNS reaction
with 2 and the yield of 3b did not decrease, which would be
expected if the added nitroarene competed with 2 in the
SET process.
1-Chloro-3-methylbutyl Phenyl Sulfone (1d): M.p. 73Ϫ74 °C
(EtOH/hexane). 1H NMR (400 MHz, CDCl3): δ ϭ 0.92 (d, J ϭ 6.4
Hz, 3 H), 1.01 (d, J ϭ 6.6 Hz, 3 H), 1.78Ϫ1.88 (m, 1 H), 1.89Ϫ1.99
(m, 1 H), 2.08Ϫ2.17 (m, 1 H), 4.68 (dd, J ϭ 11.5, 2.7 Hz, 1 H),
7.57Ϫ7.63 (m, 2 H), 7.70Ϫ7.45 (m, 1 H), 7.95Ϫ7.99 (m, 2 H) ppm.
MS (EI): m/z (%) ϭ 246 (1), 143 (100), 142 (32), 125 (7), 78 (26),
77 (26), 69 (69), 51 (13). HRMS (LSIMS, NBA): Calcd. for
C11H1635ClO2S 247.0559; found [M ϩ H]ϩ 247.0558.
1-Chlorohex-5-enyl 4-Methylphenyl Sulfone (1a): M.p. 49Ϫ50 °C
1
(EtOH/hexane). H NMR (400 MHz, CDCl3): δ ϭ 1.50Ϫ1.62 (m,
1 H), 1.70Ϫ1.89 (m, 2 H), 2.05Ϫ2.18 (m, 2 H), 2.37Ϫ2.46 (m, 1
H), 2.47 (s, 3 H), 4.63 (dd, J ϭ 10.8, 2.8 Hz, 1 H), 4.95Ϫ5.07 (m,
2 H), 5.70Ϫ5.82 (m, 1 H), 7.35Ϫ7.40 (m, 2 H), 7.80Ϫ7.85 (m, 2 H)
ppm. MS (EI): m/z (%) ϭ 157 (97), 139 (21), 116 (19), 92 (67), 91
(57), 81 (100), 65 (30). HRMS (LSIMS, NBA): Calcd. for
C13H1835ClO2S 273.0716; found [M ϩ H]ϩ 273.0718.
1-Chlorohexyl 4-Methylphenyl Sulfone (1c): M.p. 39 °C (EtOH/hex-
ane). 1H NMR (500 MHz, CDCl3): δ ϭ 0.87Ϫ0.93 (m, 3 H),
1.25Ϫ1.37 (m, 4 H), 1.39Ϫ1.50 (m, 1 H), 1.59Ϫ1.70 (m, 1 H),
1.75Ϫ1.85 (m, 1 H), 2.34Ϫ2.43 (m, 1 H), 2.47 (s, 3 H), 4.61 (dd,
J ϭ 10.9, 2.9 Hz, 1 H) 7.38 (d, J ϭ 8.0 Hz, 2 H), 7.83 (d, J ϭ 8.0
Hz, 2 H) ppm. MS (EI): m/z (%) ϭ 274 (4), 157 (100), 139 (18), 92
(55), 83 (23), 55 (41). HRMS (EI): Calcd. for C13H1935ClO2S
274.0794; found 274.0799.
Conclusion
Chloro(2,2-dimethylcyclopropyl)methyl Phenyl Sulfone (1b): (2,2-Di-
methylcyclopropyl)methyl phenyl sulfone and then dichloro(2,2-di-
methylcyclopropyl)methyl phenyl sulfone were obtained according
to the procedures published previously for the tolyl analogues.[41]
Monohydrodechlorination of the latter was accomplished by the
following procedure:
On the basis of the observations that the VNS reaction
of typical radical probes — sulfones 1a and 1b — with o-
chloronitrobenzene gave similar results as the reaction of
analogous sulfones 1c and 1d, we believe that addition of
these carbanions to nitroarenes with formation of the inter-
mediate σH adducts proceeds as a one-step ionic process
rather than by SET. Even if some electron-transfer pro-
cesses do take place in the carbanion/nitroarene system un-
der investigation, which cannot be altogether excluded, they
do not seem to interfere with the main reaction course of
the VNS, particularly the σH adduct formation. Our recent
P(NMe2)3 (547 mg, 0.61 mL, 3.35 mmol) was added in one portion
to a solution of dichloro(2,2-dimethylcyclopropyl)methyl phenyl
sulfone (651 mg, 2.23 mmol) in a mixture of DMF (5 mL) and
EtOH (0.5 mL) cooled in a water bath. The mixture was stirred for
15 min then poured into acidified water and extracted with CH2Cl2.
The extract was washed thoroughly with water and dried with
Na2SO4. The solvent was evaporated and the crude solid recrys-
tallized from MeOH. Yield 490 mg (85%), 1:1 mixture of stereoiso-
observations that the H NMR spectrum of the σH adduct
of the carbanion of chloromethyl phenyl sulfone to p-nitro-
anisole does not show paramagnetic broadening, supports
the above supposition.[19]
1
1
mers. 1b: M.p. 89Ϫ109 °C (MeOH). H NMR (200 MHz, CDCl3)
1:1 mixture of stereoisomers: δ ϭ 0.40 (dd, J ϭ 5.2, 5.6 Hz, 1 H),
0.55 (dd, J ϭ 5.1, 5.3 Hz, 1 H), 0.83 (dd, J ϭ 8.5, 5.6 Hz, 1 H),
0.85 (dd, J ϭ 9.0, 5.1, 1 H), 0.96 (s, 3 H), 1.06 (s, 3 H), 1.10 (s, 3
H), 1.13 (s, 3 H), 1.0Ϫ1.3 (m, 2 ϫ 1 H), 4.28 (d, J ϭ 11.2 Hz, 1
H), 4.39 (d, J ϭ 11.2 Hz, 1 H), 7.5Ϫ7.8 (m, 2 ϫ 3 H), 7.95Ϫ8.05
(m, 2 ϫ 2 H) ppm. MS (EI): m/z (%) ϭ 153 (12), 119 (27), 117
(85), 116 (100), 91 (21), 89 (62), 81 (86), 79 (26), 77 (29), 75 (34).
HRMS (LSIMS, NBA): Calcd. for C12H1535ClO2SNa 281.0379;
found [M ϩ Na]ϩ 281.0388.
Experimental Section
1
General Remarks: Melting points are uncorrected. H NMR spec-
tra were recorded on a Varian Mercury 400 (400 MHz) or a Bruker
DRX 500 (500 MHz) instrument at 30 °C. Chemical shifts are ex-
pressed in ppm referred to TMS, with coupling constants in hertz.
Mass spectra were obtained on an AMD-604 spectrometer. GC
analyses were performed on an HP 6890 chromatograph with HP-
5 capillary column. Silica gel Merck 60 (230Ϫ400 mesh) was used
for column chromatography.
(2,2-Dimethylcyclopropyl)methyl Phenyl Sulfone: Oil. 1H NMR
(500 MHz, CDCl3): δ ϭ 0.01 (t, J ϭ 5.2 Hz, 1 H), 0.51 (dd, J ϭ
8.7, 4.9 Hz, 1 H), 0.78 (s, 3 H), 0.83Ϫ0.91 (m, 1 H), 0.98 (s, 3 H),
3.04 (dd, J ϭ 7.2, 14.6 Hz, 1 H), 3.21 (dd, J ϭ 7.2, 14.6 Hz, 1 H),
7.54Ϫ7.59 (m, 2 H), 7.63Ϫ7.68 (m, 1 H), 7.91Ϫ7.94 (m, 2 H) ppm.
13C NMR (125 MHz, CDCl3): δ ϭ 16.1, 17.6, 19.3, 19.9, 26.4, 57.6,
128.5, 129.0, 133.6, 139.3 ppm. MS (EI): m/z (%) ϭ 143 (5), 125
Starting Materials and Reagents: 1-Chloro-3-methylbutyl phenyl
sulfone (1d), 1-chlorohexyl tolyl sulfone (1c) and 1-chlorohex-5-enyl (2), 83 (50), 82 (60), 77 (18), 67 (22), 55 (100). HRMS (ESI): Calcd.
tolyl sulfone (1a) were prepared by alkylation of the corresponding
for C12H16O2SNa 247.0763; found [M ϩ Na]ϩ 247.0777.
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Direct Nucleophilic Addition versus Single Electron Transfer
FULL PAPER
Dichloro(2,2-dimethylcyclopropyl)methyl Phenyl Sulfone: Oil. 1H
NMR (500 MHz, CDCl3): δ ϭ 0.87 (dd, J ϭ 8.4, 5.3 Hz, 1 H),
H), 1.05 (s, 3 H), 1.33 (ddd, J ϭ 11.3, 8.2, 5.2 Hz, 1 H), 3.68 (d,
J ϭ 11.3 Hz, 1 H), 7.38 (dd, J ϭ 8.5, 1.9 Hz, 1 H), 7.47Ϫ7.9 (m,
0.92 (t, J ϭ 5.6 Hz, 1 H), 1.16 (s, 1 H), 1.33 (s, 1 H), 1.88 (dd, J ϭ 7 H) ppm. MS (EI): m/z (%) ϭ 238 (100), 221 (27), 192 (45), 177
8.4, 5.6 Hz, 1 H), 7.56Ϫ7.62 (m, 2 H), 7.71Ϫ7.76 (m, 1 H), (59), 157 (28), 142 (20), 141 (19), 115 (27), 77 (16). HRMS (LSIMS,
8.06Ϫ8.09 (m, 2 H) ppm. MS (EI): m/z (%) ϭ 256 (15) [Mϩ
HCl], 216 (13), 151 (95), 150 (88), 109 (82), 79 (91), 77 (100), 51
(46). HRMS (EI): Calcd. for C12H1335ClO2S [Mϩ Ϫ HCl] 256.0325;
found 256.0314.
Ϫ
NBA): Calcd. for C18H1835ClNO4SNa 402.0543; found [M ϩ
Na]ϩ 402.0547.
1-(3-Chloro-4-nitrophenyl)hexyl 4-Methylphenyl Sulfone (3c): M.p.
1
107Ϫ109 °C (EtOH). H NMR (400 MHz, CDCl3): δ ϭ 0.8Ϫ0.9
1-Chloro-4-methylpentenyl Phenyl Sulfone (5): Bu3SnH (44.8 mg,
0.15 mmol) and a few crystals of AIBN were added to a deoxygen-
ated solution of dichloro(2,2-dimethylcyclopropyl)methyl phenyl
sulfone (18 mg, 0.062 mmol) in benzene (2 mL) under reflux. The
mixture was refluxed for 2 h, then the solvent was evaporated, the
residue dissolved in hexane and passed through a SiO2 pad, eluting
first with hexane and then with hexane/EtOAc (5:1). The latter elu-
ate was collected and the solvents evaporated to obtain a chromato-
graphically pure sample of 5, 8.5 mg, 53%; oil. 1H NMR
(500 MHz, CDCl3): δ ϭ 0.95 (d, J ϭ 6.7 Hz, 6 H), 1.87 (sept, J ϭ
6.7 Hz, 1 H), 2.20Ϫ2.25 (m, 2 H), 7.26 (q, J ϭ 7.45 Hz, 1 H),
7.54Ϫ7.59 (m, 2 H), 7.64Ϫ7.68 (m, 1 H), 7.92Ϫ7.95 (m, 2 H) ppm.
MS (EI): m/z (%) ϭ 258 (5), 216 (100), 203 (28), 181 (24), 125 (36),
77 (28). HRMS (EI): Calcd. for C12H1535ClSO2258.0481; found
[Mϩ] 258.0479.
(m, 3 H), 1.1Ϫ1.32 (m, 6 H), 2.0Ϫ2.13 (m, 1 H), 2.31Ϫ2.47 (m, 1
H), 2.43 (s, 1 H), 4.04 (dd, J ϭ 11.6, 3.8 Hz, 1 H), 7.20 (dd, J ϭ
8.4, 1.8 1 H), 7.24Ϫ7.30 (m, 3 H), 7.44Ϫ7.50 (m, 2 H), 7.79 (d,
J ϭ 8.4 Hz, 1 H) ppm. MS (EI): m/z (%) ϭ 277 (5), 275 [Mϩ
ϩ
8], 240 (18), 205 (19), 198 (13), 194 (15), 183 (100), 175 (11), 153
(15), 43 (70). HRMS (LSIMS, NBA): Calcd. for
C19H2235ClNO4SNa 418.0856; found [M ϩ Na]ϩ 418.0869.
1-(3-Chloro-4-nitrophenyl)-3-methylbutyl Phenyl Sulfone (3d): M.p.
122Ϫ123 °C (EtOH). 1H NMR (200 MHz, CDCl3): δ ϭ 0.80 (d,
J ϭ 6.6 Hz, 3 H), 0.92 (d, J ϭ 6.6 Hz, 3 H), 1.24Ϫ1.48 (m, 1 H),
2.04Ϫ2.21 (m, 2 H), 4.06Ϫ4.23 (m, 1 H), 7.19 (dd, J ϭ 8.4, 1.9 Hz,
1 H), 7.25Ϫ7.30 (m, 1 H), 7.43Ϫ7.70 (m, 5 H), 7.78 (d, J ϭ 8.4
Hz, 1 H) ppm. MS (EI): m/z (%) ϭ 226 (54), 184 (100), 165 (24),
140 (20), 125 (16), 102 (16), 77 (68). HRMS (LSIMS, NBA): Calcd.
for C17H1935ClNO4S 368.0723; found [M ϩ H]ϩ 368.0690.
All other reagents are commercially available.
2-Chloro-4-(1-chlorohex-5-enyl)-1-nitrobenzene (4a): Oil. 1H NMR
(200 MHz, CDCl3): δ ϭ 1.1Ϫ2.2 (m, 6 H), 4.77Ϫ4.89 (m, 1 H),
4.92Ϫ5.15 (m, 2 H), 5.65Ϫ5.9 (m, 1 H), 7.42 (dd, J ϭ 8.3, 1.9 Hz,
1 H), 7.58 (d, J ϭ 1.9 Hz, 1 H), 7.88 (d, J ϭ 8.3 Hz, 1 H) ppm.
MS (EI): m/z (%) ϭ 275 (9), 273 (14), 256 (3), 238 (22), 217 (15),
183 (100), 153 (45), 115 (53). HRMS (EI): Calcd. for
C12H1335Cl2NO2 273.0323; found [Mϩ] 273.0348.
General Procedure for the Reactions of Chlorosulfones 1a؊d with 2-
Chloronitrobenzene (2):
KOH/DMSO System: Powdered KOH (0.2 g) was stirred magneti-
cally in DMSO (1 mL) under Ar for 15 min. A solution of 2 (76 mg,
0.5 mmol) and the appropriate chlorosulfone 1aϪd (0.5 mmol) in
DMSO (1 mL, deoxygenated with Ar) was then added dropwise
during about 30 s. The reaction mixture was stirred for 60 min at
ambient temperature, then poured into acidified water and ex-
tracted with dichloromethane. The extract was washed with water,
dried with MgSO4 and analysed by GC. Pure samples of the prod-
ucts were obtained by column chromatography of the crude prod-
uct mixtures (SiO2, hexane/EtOAc).
2-Chloro-4-(1-chlorohexyl)-1-nitrobenzene (4c): Oil. 1H NMR
(400 MHz, CDCl3): δ ϭ 0.85Ϫ0.93 (m, 3 H), 1.26 Ϫ1.60 (m, 6 H),
1.93Ϫ2.14 (m, 2 H), 4.82, (dd, J ϭ 6.2, 8.2 Hz, 1 H), 7.42 (dd, J ϭ
8.4, 2.0 Hz, 1 H), 7.57 (d, J ϭ 2.0 Hz, 1 H), 7.88 (d, J ϭ 8.4 Hz,
1 H) ppm. MS (EI): m/z (%) ϭ 277 (5), 275 [Mϩ ϩ 8], 240 (18),
205 (19), 194 (15), 183 (100), 170 (13), 153 (15), 43 (70). HRMS
(EI): Calcd. for C12H1535Cl2NO2 275.0480; found [Mϩ] 275.0482.
tBuOK/DMSO System: According to the above procedure, but
with tBuOK (246 mg, 2.2 mmol) instead of KOH. Reaction time
2 min.
2-Chloro-4-(1-chloro-3-methylbutyl)-1-nitrobenzene (4d): Oil. 1H
NMR (500 MHz, CDCl3): δ ϭ 0.96 (d, J ϭ 6.4 Hz, 3 H), 0.97 (d,
J ϭ 6.4 Hz, 3 H), 1.74Ϫ1.82 (m, 2 H), 1.98Ϫ2.08 (m, 1 H), 4.88
(dd, J ϭ 9.2, 5.5 Hz, 1 H), 7.42 (dd, J ϭ 8.4, 1.9 Hz, 1 H), 7.57
(d, J ϭ 1.9 Hz, 1 H), 7.88 (d, J ϭ 8.4 Hz, 1 H) ppm. MS (EI):
m/z (%) ϭ 261 (24), 226 (21), 205 (86), 184 (28), 170 (13), 123
(11), 75 (13), 57 (100). HRMS (EI): Calcd. for C11H1335Cl2O2N
261.0323; found [Mϩ] 261.0321.
tBuOK/DMF System: Procedure as above, with DMF instead of
DMSO and temperature maintained at Ϫ40 °C. Reaction time
5 min.
2-Chloro-4-{1-[(4-methylphenyl)sulfonyl]hex-5-enyl}-1-nitrobenzene
(3a): M.p. 88 °C (EtOH). 1H NMR (200 MHz, CDCl3): δ ϭ
1.15Ϫ1.4 (m, 2 H), 1.95Ϫ2.2 (m, 3 H), 2.3Ϫ2.45 (m, 1 H), 2.44 (s,
3 H), 4.05 (dd, J ϭ 11.5, 3.8 Hz, 1 H), 4.9Ϫ5.02 (m, 2 H),
5.55Ϫ5.80 (m, 1 H), 7.20 (d, J ϭ 8.3 Hz, 1 H) ppm. MS (EI): m/z
(%) ϭ 240 (32), 238 (100), 221 (21), 196 (11), 194 (12), 192 (38),
184 (21),157 (44), 150 (27), 140 (17),115 (20), (1 (31), 67 (18).
HRMS (LSIMS, NBA): Calcd. for C19H2135ClNO4S 394.0880;
found [M ϩ H]ϩ 394.0867.
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Received January 19, 2004
2130
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 2125Ϫ2130