Selenium halide-induced bridge formation in [2.2]paracyclophanes

Article abstract of DOI:10.3762/bjoc.10.266

An addition/elimination sequence of selenium halides to pseudo-geminally bis(acetylene) substituted [2.2]paracyclophanes leads to new bridges with an endo -exo-diene substructure. The reactions have been found to be sensitive to the substitution of the ethynyl group. The formation of dienes with a zig-zag configuration is related to that observed for non-conjugated cyclic diynes of medium ring size.

Full text of DOI:10.3762/bjoc.10.266

Selenium halide-induced bridge formation
in [2.2]paracyclophanes
Laura G. Sarbu1, Henning Hopf2, Peter G. Jones3 and Lucian M. Birsa*1,2
Full Research Paper
Open Access
Address:
Department of Chemistry,“Al. I. Cuza” University of Iasi, 11 Carol I
Beilstein J. Org. Chem. 2014, 10, 2550–2555.
1
doi:10.3762/bjoc.10.266
Bv., RO-700506 Iasi, Romania, 2Institute of Organic Chemistry,
Technical University of Braunschweig, Hagenring 30, D-38106
Braunschweig, Germany and 3Institute of Inorganic and Analytical
Chemistry, Technical University of Braunschweig, Hagenring 30,
D-38106 Braunschweig, Germany
Received: 12 July 2014
Accepted: 17 October 2014
Published: 31 October 2014
Associate Editor: D. O'Hagan
Email:
Lucian M. Birsa* - lbirsa@uaic.ro
© 2014 Sarbu et al; licensee Beilstein-Institut.
License and terms: see end of document.
*
Corresponding author
Keywords:
acetylenes; dienes; [2.2]paracyclophane; selenium halides
Abstract
An addition/elimination sequence of selenium halides to pseudo-geminally bis(acetylene) substituted [2.2]paracyclophanes leads to
new bridges with an endo-exo-diene substructure. The reactions have been found to be sensitive to the substitution of the ethynyl
group. The formation of dienes with a zig-zag configuration is related to that observed for non-conjugated cyclic diynes of medium
ring size.
Introduction
Starting with their discovery in 1949, the [2.2]paracyclophane undergo highly specific reactions. This is due to the rigid frame-
molecule and its derivatives have been intensely studied [1-3]. work and the short distance between the two aromatic rings
Of particular interest are the geometry and transannular interac- within the [2.2]paracyclophane unit. Thus, unsaturated cyclo-
tions of these molecules, the study of electrophilic aromatic phane bis(esters) undergo intramolecular photocyclization,
substitution reactions involving these systems and their ability yielding the corresponding ladderane isomers [9-11]. The
to form charge-transfer complexes [4-7]. Much attention is also ethynyl group is well known for its ability to undergo coupling
being paid to the development of new functionalized [2.2]para- reactions, making the pseudo-geminal bis(acetylene) 1 and its
cyclophanes that can be used in asymmetric synthesis [8], while derivatives good candidates for building molecular scaffolding
the formation of new bridges, particularly functionalized ones, [12,13]. The reaction between bis(acetylene) 1 and other acety-
has been somewhat neglected so far. Functional groups in lene derivatives has been reported to provide new π-bridges in
pseudo-geminally substituted [2.2]paracyclophanes often [2.2]paracyclophane [14].
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Furthermore, a new way for bridging [2.2]paracyclophanes has H20. These products were obtained in a 1:1.5:0.5 ratio and an
been accomplished by the addition of selenium monochloride to isolated yield of 72% (Table 1, entry 1).
pseudo-geminally substituted bis(propargylic) alcohols [15].
Organoselenium chemistry has become widely used in organic
Table 1: Addition reactions to bis(acetylene) 1.
synthesis, because of the availability of both electrophilic and
nucleophilic selenium species [16]. The fundamental aspects of
organoselenium chemistry have been comprehensively
described in monographs and review articles [17-20]. For elec-
trophilic selenium species, most of the investigations have been
carried out in order to study the addition mechanism of sele-
nium halides to alkenes [21-23]. Less work has been reported
on the addition of selenyl reagents to alkynes [24,25]. In
contrast to the chemistry of sulfur halides, selenium elec-
trophiles undergo smooth 1,2-additions to triple bonds, leading
to the formation of functionalized vinyl selenides [26]. It has
been reported that the addition of electrophilic selenium
reagents to alkynes preferably yields the corresponding
E-adducts [27].
Entry SeX2, equiv
Ratio of products
Yielda
2
3
4
1
2
SeCl2, 1 equiv
SeCl2, 2 equiv
1
1
1.5
1.3
0.5
–
72
70
5
6
7
3
4
SeBr2, 1 equiv
SeBr2, 2 equiv
1
1
1.4
1.3
0.3
–
76
73
aTotal isolated yield.
Analogously, the reaction of 1 with one equivalent of in situ
prepared SeBr2 [28], in chloroform at 0 °C, provided a mixture
In continuation of our investigations on the intramolecular inter- of isomeric cyclic dienes 5 and 6, and the tetrabromo derivative
action of chemically disturbed functional groups in pseudo- 7 (Scheme 1, Table 1, entry 3) in 76% yield. Again, the struc-
geminally substituted [2.2]paracyclophanes, we report here the tures of these compounds, as well as the configuration of diene
results of the addition reactions of selenium halides to pseudo- 5, have been established on the basis of 2D NMR studies, mass
geminal bis(acetylenes).
spectrometry analysis and a mutual NOE between H18 and
H20. The relative Z stereochemistry of tetrabromo derivative 7
was unambiguously established by X-ray analysis; however,
Results and Discussion
Following our interest in the introduction of new bridges to there is a disordered carbon–bromine bond and the structure
2.2]paracyclophanes, we decided to investigate a double addi- could not be completely refined. The ratio of 5 and 6 was deter-
[
tion reaction of 1 equiv of selenium dichloride to both mined as 1:1.4. It is interesting to note that the synthesis of the
triple bonds of 4,13-bis(ethynyl)[2.2]paracyclophane 1; a [2.3.2](1,2,4)cyclophane derivative 5 has been previously
bis(vinyl)selenide bridge should result from this interaction. reported as the result of bromine addition to bis(acetylene) 1, in
Thus, by reacting 1 with one equivalent of in situ prepared 87% yield [13].
SeCl2 [28], in chloroform at 0 °C, a mixture of unexpected ad-
dition products has been obtained (Scheme 1). After separation In both experiments, the formation of elemental red selenium
by column chromatography, we assigned the structures of was observed. The unexpected reaction products result from the
isomeric cyclic dienes 2 and 3 and the tetrachloro derivative 4 equimolar interaction of bis(acetylene) 1 with selenium
on the basis of 2D NMR studies and mass spectrometric dihalides; the tetrahalide derivatives 4 and 7, in particular,
analysis. The configuration of compound 2 as a (17E,19E)- prompted us to investigate the interaction of 1 with 2 equiv of
diene was established from the mutual NOEs between H18 and these selenium derivatives. Under the same experimental condi-
Scheme 1: Reactions of selenium dichloride and selenium dibromide with pseudo-geminal bis(acetylene) 1.
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tions, using 2 equiv of selenium dichloride or selenium dibro- involves, in a first step, the addition of one equivalent of
mide, we isolated only the [2.3.2](1,2,4)cyclophane derivatives PhSeCl to one of the triple bonds of 1 resulting in the forma-
2
, 3 and 5, 6, respectively; no traces of tetrahalides 4 and 7 were tion of episelenonium ion 8 (Scheme 3). The episelenonium ion
detected (Table 1, entries 2 and 4). Although unexpected, the 8 should equilibrate with the ring-opened form, a benzylic type
lack of tetrahalides from these experiments proved later to be of carbocation; the interaction of this intermediate with the
significant importance for the reaction mechanism of selenium opposing ethynyl substituent provides adduct 9. For steric
dihalide addition to pseudo-geminal bis(acetylene) 1.
reasons the chlorine anion attack from "outside" leading to
intermediate 10. The reaction of 10 with the second equivalent
The unexpected formation of [2.3.2](1,2,4)cyclophane deriva- of PhSeCl leads to selenonium ion 11; once the diphenyl dise-
tives 2, 3 and 5, 6, then induced us to investigate the addition lenide leaving group is formed, the addition of chloride counter-
reaction of phenylselenyl chloride to 4,13-bis(ethyn- anions from both directions is accompanied by the formation of
yl)[2.2]paracyclophane. Surprisingly, the addition of 2 equiv of [2.3.2](1,2,4)cyclophane derivatives 2 and 3. Most probably
PhSeCl to bis(acetylene) 1 again provided a mixture of dienes 2 compound 3 is formed under kinetic control, diene 2 being ther-
and 3 along with diphenyl diselenide, in a 70% total isolated modynamically more stable.
yield (Scheme 2).
With regard to the addition of selenium dihalides to bis(acety-
lene) 1, the reaction mechanism should follow a similar course,
consisting of the formation of a selenonium ion of type 10
rather than the addition of the selenium electrophiles to the
second triple bond. This involves elimination of diselenium
dihalides with the formation of dienes 2, 3 and 5, 6. The forma-
tion of diselenium dihalides appears to be correlated with the
Scheme 2: Reaction of phenylselenyl chloride with pseudo-geminal
bis(acetylene) 1.
presence of tetrahalides 4 and 7 among the reaction products
when only one equivalent of selenium dihalides is used. Disele-
nium dihalides could be the source for the remaining two
The ratio of isomeric dienes 2 and 3 was again 1:1.5, as resulted halogen atoms either by disproportionation, which generates
from the SeCl2 addition to 4,13-bis(ethynyl)[2.2]paracyclo- molecular chlorine or bromine [30], or/and by decomposition
phane. Moreover, an important experimental observation was (e.g., Se2Br2 + Br− → BrSeSe− + Br2). As mentioned before,
the fact that diphenyl diselenide was formed in an equimolar we always noticed the formation of elemental red selenium.
amount with the isomeric dienes. This indicates a common These assumptions are supported by the outcome of the reac-
intermediate for the reaction products from which elimination tion when 2 equiv of selenium dihalides were used (Table 1,
of diphenyl diselenide provides dienes 2 and 3.
entries 2 and 4).
Based on previously reported investigations on the mechanism The fact that the ratio of the isomeric dienes is almost identical
of the reaction of phenylselenyl chloride with selected steri- with those determined for entries 1 and 3, together with the lack
cally hindered alkenes [29], the most probable mechanism of tetrahalide derivatives, suggests that the second equivalent of
Scheme 3: Plausible reaction mechanism for the addition of phenylselenyl chloride to pseudo-geminal bis(acetylene) 1.
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Beilstein J. Org. Chem. 2014, 10, 2550–2555.
selenium dihalide acts as described in Scheme 3 for phenylse- compound was unambiguously proved by X-ray crystallog-
lenyl chloride. This reaction appears to be faster than the raphy (Figure 1). A colourless tablet 0.35 × 0.2 × 0.08 mm was
involvement of diselenium dihalides in generation of tetra- used to record intensity data to 2θ 56.6° on an Oxford Diffrac-
halides 4 and 7 from incompletely reacted starting materials. tion Xcalibur E diffractometer using monochromated Mo Kα
Although our synthetic procedure involves an addition/elimina- radiation (λ = 0.71073 Å). Crystal data: C22H20Cl2, monoclinic,
tion protocol of selenium derivatives, the formation of isomeric P21/c, a = 9.0685(3), b = 8.0240(3), c = 23.1441(8) Å,
endo-exo-dienes 2, 3 and 5, 6 resembles the zig-zag cycliza- β = 93.423(3)° (at 100 K), Z = 4. Structure refinement: The
tions of nonconjugated cyclic diynes of medium ring size structure was treated as a non-merohedral twin (by 180° rota-
reported by Gleiter [31,32].
tion about the a axis). Refinement on F2 using the program
SHELXL-97 [33] proceeded to wR2 0.117 (all data), R1 0.046
In order to check the limits of these selenium-mediated (F > 4σ(F)), twinning ratio 0.0481(6), S = 1.05, Δρ = 0.4 e Å–3.
intramolecular interactions, we decided to extend the study to CCDC-997241 contain the supplementary crystallographic data
another pseudo-geminal bis(acetylene), 4,13-bis(propyn-1- for compound 13. These data can be obtained free of charge
yl)[2.2]paracyclophane 12 (Scheme 4). Thus, by reacting from the Cambridge Crystallographic Data Centre via http://
bis(acetylene) (12) with 1 equiv of selenium dichloride we www.ccdc.cam.ac.uk/data_request/cif. Furthermore, the reac-
isolated only the (17E,19E)-diene 13 and tetrachloride deriva- tion of 12 with 1 equiv of selenium dibromide follows the same
tive 14 in 76% yield (Table 2, entry 1). The lack of isomeric course, providing only (17E,19E)-diene 15 and tetrabromide
diene (17E,19Z) could be explained as the result of steric hin- derivative 16 in 64% yield (Table 2, entry 4).
drance induced by the presence of methyl groups at the acety-
lenic carbon atoms. This forces the addition of a chloride anion
to a methylated intermediate of type 11 to take place in the way
that provides only the thermodynamically stable (17E,19E)-
[
2.3.2](1,2,4)cyclophane derivative 13. The structure of this
Table 2: Addition reactions to 4,13-bis(propyn-1-yl)[2.2]paracyclo-
phane 12.
Entry
Selenium electrophile,
equiv
Ratio of
products
Yielda
13
14
1
2
3
SeCl2, 1 equiv
SeCl2, 2 equiv
PhSeCl, 2 equiv
1
1
0.6
–
76
70
56
1b
–
15
16
4
5
SeBr2, 1 equiv
SeBr2, 2 equiv
1
1
0.6
–
64
62
Figure 1: Molecular structure of compound 13. Ellipsoids represent
50% probability levels. Selected molecular dimensions (Å, °): C17–C20
1.337(3), C18–C19 1.341(3), C18–C19–C4 128.9(2), C17–C20–C21
129.3(2).
aTotal isolated yield. bAlong with an equimolar amount of diphenyl
diselenide.
Scheme 4: Reactions of selenium dichloride and selenium dibromide with 4,13-bis(propyn-1-yl)[2.2]paracyclophane (12).
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9
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Desvergne, J.-P.; Bouas-Laurent, H. Eur. J. Org. Chem. 2005,
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In support of the proposed reaction mechanism, the reaction of
,13-diyne 12 with 2 equivalents of selenium dichloride or sele-
4
5
nium dibromide provided only (17E,19E)-diene 13 and 15;
1
0.Hopf, H.; Greiving, H.; Beck, C.; Dix, I.; Jones, P. G.; Desvergne, J.-P.;
Bouas-Laurent, H. Eur. J. Org. Chem. 2005, 567–581.
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again, no traces of tetrahalide derivatives were identified
(
Table 2, entries 2 and 5). The addition of phenylselenyl chlo-
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mechanism, as only diene 13, along an equimolar amount of
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