Synthesis of α,β-unsaturated Pseudogeminal [2.2]paracyclophane bisketones

Article abstract of DOI:10.1055/s-2007-991050

An unexpected synthesis of α,β-unsaturated pseudogeminal [2.2]paracyclophane bisketones has been realized via a dyotropic-type rearrangement of the corresponding bisallenyl o-nitrophenyl sulfoxides. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-991050

LETTER
2753
Synthesis of a,b-Unsaturated Pseudogeminal [2.2]Paracyclophane Bisketones
a
,
b
-Unsaturated Pseud
.
ogeminal [2.
L
2]Paracyclopha
u
ne Bisketone
c
s
ian Birsa,*a,b Henning Hopfa
b
Received 23 July 2007
O
..
CCl3
Abstract: An unexpected synthesis of a,b-unsaturated pseudo-
geminal [2.2]paracyclophane bisketones has been realized via a
dyotropic-type rearrangement of the corresponding bisallenyl o-
nitrophenyl sulfoxides.
S
R
R
..
S
CCl3
Key words: [2.2]paracyclophanes, sulfoxides, allenes, rearrange-
ment
O
1
Figure 1
Because of the rigid molecular framework provided by the
paracyclophane unit and its short interannular distance,
functional groups in pseudogeminally substituted
[2.2]paracyclophanes are often held in such a position as
to allow highly specific reactions to take place between
them. In one such application unsaturated cyclophane
bisesters undergo intramolecular photocyclization to the
corresponding ladderane isomers.1–3
chloride via a double [2,3]-sigmatropic rearrangement of
the corresponding sulfenyl esters (Scheme 1).5,6
Following the above protocol, o- and p-nitrophenyl sulf-
oxides were obtained in good yields (50–55%) as bright
yellow solids.7 As expected, a mixture of four diastereo-
isomers was isolated in all cases.
Mass spectrometric analysis of the above compounds
revealed an unexpected sensitivity of the o-nitrophenyl
sulfoxide derivatives towards EI conditions. In both cases
(3a and 3b) a molecular ion of m/z = 308 (C12H8N2O4S2)
was recorded. However under ESI conditions the molecu-
lar mass of the above sulfoxides (C40H38N2O6S2 and
C36H30N2O6S2, respectively) was confirmed.
Using pseudogeminally substituted [2.2]paracyclophanes
as spacers for bisallenic moieties, interesting starting
materials for intra- or intermolecular reactions can be re-
alized. In a recent paper we have reported on the synthesis
of first bisallenyl-substituted pseudogeminal [2.2]para-
cyclophanes 1.4 Although the distance between two allen-
ic moieties should allow intramolecular interactions, none
of these have been observed under various conditions.
In order to elucidate the chemical process that took place
under thermal conditions, we gently heated a solution of 3
at 40 °C. After 18 hours the starting material was
consumed and from the mixture of diastereoisomers a
symmetrical compound could be isolated. Valuable infor-
mation was obtained by NMR monitoring. The spectra of
the crude product showed a clean and symmetrical ali-
phatic area, a doublet with J = 12 Hz (d = 6.05 ppm), and
a complex aromatic area in comparison with the o-nitro-
phenyl pattern. Separation by silica gel column chroma-
tography indicated the formation of two major
The lack of reactivity of these unsaturated systems could
be due to both electronic and steric effects of the trichlo-
romethyl sulfoxide or sulfone substituents, respectively.
In order to get a deeper insight into this phenomenon we
decided to replace the trichloromethyl group with a nitro-
phenyl substituent. This was accomplished by the reaction
of bispropargylic alcohols 2a,b with nitrobenzenesulfenyl
O
..
S
Cl
C6H4NO2
S
R
R
CH2Cl2, Et3N
2 x [2,3]-σ
R
C6H4NO2
R
+
R
S
OH
OH
–78 °C to r.t.
O
R
..
S
C6H4NO2
C6H4NO2
NO2
S
O
O
2a,b
3a–c
3a R = n-Pr, C6H4NO2 (ortho)
3b R = Me, C6H4NO2 (ortho)
3c R = n-Pr, C6H4NO2 (para)
2a R = n-Pr
2b R = Me
Scheme 1
SYNLETT 2007, No. 17, pp 2753–2755
1
6
.1
0
.
2
0
0
7
Advanced online publication: 25.09.2007
DOI: 10.1055/s-2007-991050; Art ID: G24607ST
© Georg Thieme Verlag Stuttgart · New York

2754
M. L. Birsa, H. Hopf
LETTER
O
..
C6H4NO2
NO2
S
H
CH2Cl2, 18 h
40 °C
O
R
+
S
S
R
H
H
R
..
S
C6H4NO2
O
NO2
H
O
R
3a,b
4a,b
3a R = n-Pr, C6H4NO2 (ortho)
3b R = Me, C6H4NO2 (ortho)
4a R = n-Pr
4b R = Me
5
Scheme 2
compounds, an a,b-unsaturated ketone 4 and bis(o-nitro- Consequently, it is reasonable to assume that the forma-
phenyl) disulfide 5 (MW = 308, ca. 15% isolated yield; tion of a,b-unsaturated ketone is initiated by an interac-
Scheme 2). The formation of disulfide 5, a known com- tion between the electron pairs of the sulfur and nitrogen
pound, was unambiguously proven by X-ray structural atoms, making the system flat and inducing a high rota-
analysis. Although the spectra of the crude mixture tional barrier around the S–CAr bond (Figure 1).
revealed the formation of the cis isomer only, during pu-
No deuterium incorporation was observed when
pseudogeminal bisallenyl sulfoxides were heated in
CDCl3 at 40 °C. Finally, a radical mechanism appeared
rification isomerization took place and the thermodynam-
ically more stable trans isomer 4 was isolated.8
Interestingly, under the same experimental conditions the reasonable after an experiment in the presence of the free
corresponding p-nitrophenyl sulfoxide 3c was found to be radical inhibitor hydroquinone. No reaction was observed
stable. This observation indicates that the above reaction during two days.
may be a special case due to the ortho orientation of the
nitro group towards the sulfoxide unit. In order to eluci-
date some mechanistic aspects we decided to investigate
whether the reaction took place only in case of the o-nitro-
Taking these results into account, we postulate the follow-
ing mechanism for the conversion of 3a,b into 4a,b. In the
first step 3 closes to the diradical 8, which then undergoes
a dyotropic rearrangement11,12 as shown in Scheme 4.
phenyl sulfoxide pattern, whether the pseudogeminal
substitution favored an intramolecular interaction, and
whether the process involved radical or anionic inter-
mediates.
R
R
Ar
Ar
S
S
O:
:
:
3a,b
4a,b
+
+ polysulfides
S
O:
Thus, we oxidized the o-nitrophenyl sulfoxide 3a to the
corresponding sulfone, using dimethyldioxirane (DMDO)
as the oxidant. The sulfone was obtained as a single iso-
mer in 20% isolated yield. Despite of the low yield ob-
tained, no reaction or decomposition was observed during
two weeks.
S
Ar
Ar
8
Scheme 4
The formation of 4 requires two additional hydrogen
atoms. Corroborating that with the low yield for the di-
sulfide (ca. 15%) one can assume that the aromatic ring of
the o-nitrophenyl sulfoxide unit may be the source of
hydrogen atoms. The formation of polymeric sulfides is
indicated by the crowded aromatic area in the spectra of
crude reaction products.
Moreover, in order to check whether the a,b-unsaturated
ketone had been formed by an intramolecular interaction
or from independent interactions between allenic and
sulfoxide units we investigated the chemical behavior of
allenyl sulfoxide 7 under the same experimental condi-
tions. This compound was prepared from 1-hydroxy-1-
phenylbut-2-yne (6) following the procedure described
above (Scheme 3). Sulfoxide 7 was obtained as a mixture
of two diastereoisomers.9
In conclusion, we have discovered an interesting intra-
molecular reaction of pseudogeminal bisallenyl o-nitro-
phenyl sulfoxide systems that is presumably caused by an
interaction between nitro and sulfoxide groups. Evidence
for a radical mechanism via a dyotropic-type rearrange-
ment has been presented. The formation of the
pseudogeminal a,b-unsaturated ketone 4 has opened a
way towards ladderane-type compounds.
Indication for an intramolecular interaction in bisallenyl
sulfoxides 3a,b is supported by the fact that no chemical
reaction of 7 was observed under the same experimental
conditions. A survey of literature data on ortho-substi-
tuted phenyl sulfoxides revealed that mono-ortho-sub-
stitution prevents free rotation of the S(O)R group.10
Ph
Me
S
CH2Cl2, Et3N
–78 °C to r.t.
+
Me
ClS
O2N
Ph
OH
O
6
7
O2N
Scheme 3
Synlett 2007, No. 17, 2753–2755 © Thieme Stuttgart · New York

LETTER
a,b-Unsaturated Pseudogeminal [2.2]Paracyclophane Bisketones
2755
for one isomer). MS–ESI: m/z = 729 [M+ + 23]. Anal. Calcd
for C40H38N2O6S2: C, 67.97; H, 5.42; N, 3.96; S, 9.07.
Found: C, 67.79; H, 5.24; N, 3.77; S, 9.17.
Acknowledgment
The authors would like to thank Prof. S. Braverman (Bar Ilan Uni-
versity, Israel) for helpful discussions concerning allenyl sulfoxi-
des. M.L.B. is indebted to the Alexander von Humboldt Foundation
for a short stay at Braunschweig. Part of this work has been suppor-
ted by the Romanian CEEX Program.
(8) Compound 4a (0.17 g, 85%); viscous oil. IR (neat): 2960,
1683, 1655, 1584, 1366, 1183, 728 cm–1. 1H NMR (200
MHz, CDCl3, TMS): d = 0.97 (t, 3J = 7 Hz, 6 H, 2 × Me),
1.62 (sext, 3J = 7 Hz, 4 H, 2 × CH2), 2.54 (t, 3J = 7 Hz, 4 H,
2 × CH2), 3.05 (m, 6 H, 3 × CH2), 3.09 (m, 1 H, CH2), 3.61
(m, 1 H, CH2), 6.37 (d, 3J = 16 Hz, 2 H, 2 × CH), 6.56 (m, 4
H, 4 × CHAr), 6.74 (m, 2 H, 2 × CHAr), 7.60 (d, 3J = 16 Hz, 2
H, 2 × CH). 13C NMR (50 MHz, CDCl3, TMS): d = 13.7 (q),
17.5 (t), 32.6 (t), 34.8 (t), 42.5 (t), 126.4 (d), 130.2 (d), 134.7
(s), 134.8 (d), 135.1 (d), 139.4 (d), 139.9 (s), 140.0 (s), 200.1
(s). MS–EI: m/z (%) = 400 (20) [M+], 383 (15), 329 (25), 187
(21), 129 (100). Anal. Calcd for C28H32O2: C, 83.96; H, 7.99.
Found: C, 83.64; H, 7.70.
References and Notes
(1) Greiving, H.; Hopf, H.; Jones, P. G.; Bubenitschek, P.;
Desvergne, J.-P.; Bouas-Laurent, H. Eur. J. Org. Chem.
2005, 558.
(2) Hopf, H.; Greiving, H.; Beck, C.; Dix, I.; Jones, P. G.;
Desvergne, J.-P.; Bouas-Laurent, H. Eur. J. Org. Chem.
2005, 567.
(9) Compound 7 (0.25 g, 85%); viscous oil. IR (neat): 2954,
1974, 1534, 1342, 1052, 729 cm–1. 1H NMR (200 MHz,
CDCl3, TMS): d = 2.05 (t, 5J = 3.3 Hz, 3 H, Me), 6.15 (t,
5J = 3.3 Hz, 1 H, CHallene), 7.00 (m, 2 H, 2 × CHAr), 7.15 (m,
3 H, 3 × CHAr), 7.31 (m, 1 H, CHAr), 7.52 (m, 1 H, 2 × CHAr),
7.75 (m, 1 H, CHAr), 8.22 (m, 1 H, CHAr) (selected NMR
data for one isomer). 13C NMR (50 MHz, CDCl3, TMS): d =
13.0 (q), 100.4 (d), 112.5 (s), 125.0 (s), 126.3 (d), 126.9 (d),
127.0 (d), 127.1 (d), 127.3 (d), 128.1 (d), 128.6 (d), 128.7
(d), 131.3 (s), 134.5 (d), 134.8 (s), 203.6 (s) (selected NMR
data for one isomer). MS (ESI): m/z = 322 [M+ + 23]. Anal.
Calcd for C16H13NO3S: C, 64.20; H, 4.38; N, 4.68; S, 10.71.
Found: C, 63.94; H, 4.19; N, 4.54; S, 10.48.
(10) Baliah, V.; Ekambaram, A. J. Indian Chem. Soc. 1991, 68,
272.
(11) For reviews see: (a) Minkin, V. I.; Olekhnovich, L. P.;
Zhdanov, Y. A. Molecular Design of Tautomeric
Compounds; D. Reidel Publishing Co.: Dordrecht, 1988,
221. (b) Reetz, M. T. Adv. Organomet. Chem. 1977, 16, 33.
(12) Mackenzie, K.; Proctor, G.; Woodnutt, D. J. Tetrahedron
1987, 43, 5981; and references cited therein.
(3) For a review, see: Hopf, H. Angew. Chem. Int. Ed. 2003, 42,
2822; Angew. Chem. 2003, 115, 2928.
(4) Birsa, M. L.; Jones, P. G.; Braverman, S.; Hopf, H. Synlett
2005, 640.
(5) Braverman, S. In The Chemistry of Sulfenic Acids and their
Derivatives; Patai, S., Ed.; Wiley: New York, 1990, 311.
(6) Braverman, S. In The Chemistry of Double-Bonded
Functional Groups, Supplement A2; Patai, S., Ed.; Wiley:
Chichester, 1989, 963.
(7) Compound 3a (0.35 g, 50%); mp 118–119 °C. IR (neat):
2927, 1960, 1515, 1337, 1063, 733 cm–1. 1H NMR (200
MHz, CDCl3, TMS): d = 1.05 (t, 3J = 7 Hz, 6 H, 2 × Me),
1.62 (sext., 3J = 7 Hz, 4 H, 2 × CH2), 2.47 (dt, 3J = 7, 5J = 3
Hz, 4 H, 2 × CH2), 2.95 (m, 6 H, 3 × CH2), 3.05 (m, 1 H,
CH2), 3.42 (m, 1 H, CH2), 6.38 (m, 6 H, 6 × CHAr), 6.58 (t,
5J = 3 Hz, 2 H, 2 × CHallene), 7.40 (m, 2 H, 2 × CHAr), 7.65
(m, 2 H, 2 × CHAr), 7.88 (m, 2 H, 2 × CHAr), 8.35 (m, 2 H,
2 × CHAr) (selected NMR data for one isomer). 13C NMR (50
MHz, CDCl3, TMS): d = 13.9 (q), 21.5 (t), 30.1 (t), 32.3 (t),
34.7 (t), 101.6 (d), 115.9 (s), 124.1 (d), 125.2 (d), 126.4 (d),
131.0 (d), 132.9 (d), 133.2 (d), 133.5 (d), 135.2 (s), 137.8 (s),
140.0 (s), 142.1 (s), 144.3 (s), 204.6 (s) (selected NMR data
Synlett 2007, No. 17, 2753–2755 © Thieme Stuttgart · New York

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