Synthesis of cyclophanetetrayne complexes from bis(propargyldicobalt) dication equivalents

Article abstract of DOI:10.1039/b203187f

Nicholas reactions of the p-phenyl linked bis(propargyl acetate) complex (3a) with electron rich arenes give cyclophanetetrayne complexes (5). The use of bis(propargyl ether) complex (8) with (3a) allows formation of a mixed cyclophanetetrayne complex (9), and in addition gives retro-Nicholas/intramolecular Nicholas reaction product (2).

Full text of DOI:10.1039/b203187f

Synthesis of cyclophanetetrayne complexes from bis(propargyldicobalt)
dication equivalents†
Romelo Gibe and James R. Green*
Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON N9B 3P4, Canada.
E-mail: jgreen@uwindsor.ca; Fax: (519)-973-7098; Tel: (519)-253-3000, Ext.3545
Received (in Corvallis, OR, USA) 2nd April 2002, Accepted 6th May 2002
First published as an Advance Article on the web 19th June 2002
Nicholas reactions of the p-phenyl linked bis(propargyl
acetate) complex (3a) with electron rich arenes give cyclo-
phanetetrayne complexes (5). The use of bis(propargyl
ether) complex (8) with (3a) allows formation of a mixed
cyclophanetetrayne complex (9), and in addition gives retro-
Nicholas/intramolecular Nicholas reaction product (2).
equiv.) of 1,3,5-trimethoxybenzene and 3 equiv. of BF3–OEt2,
diarylation product 4a was formed in 90% yield. In contrast, at
2 3 1023 M of 3a (CH2Cl2, 5 °C, 12 h), with 1.0 equiv. of
1,3,5-trimethoxybenzene and a large excess of BF3–OEt2 (9
equiv.),
a different predominant discrete product, the
[3.3.3.3]m,p,m,p-cyclophanetetrayne complex 5a, was isolated
Alkyne-containing cyclophane molecules have been the subject
of intense recent research activity. Reasons for this attention
include their syntheses as enediyne antitumour analogues/
Bergman cyclization precursors,1 the design of cyclophanes
with shape persistent cavities,2 the metal complexation or self
aggregation abilities of these compounds,3 interest in systems
containing extended p-conjugation,4 their use as fullerene
precursors,5 and questions of stability versus angle strain on the
alkyne unit. 6,7
The synthetic chemistry of hexacarbonyldicobalt alkyne
complexes also has been a topic of widespread interest,8 due to
the ability of the group to participate in novel cycloaddition
reactions,9,10 to enable the facile formation and trapping of
cations in the propargylic position (the Nicholas reaction),11 and
to allow bond geometries not available to the metal free alkyne
function. We have been engaged in the study of the use of these
complexes, predominantly in their use in tandem Nicholas
reactions towards a number of synthetic ends.12,13 One of the
most significant manifestations of this work has been the
discovery that electron rich arenes and heteroarenes react with
complex 1 to rapidly assemble [7]metacyclophanediyne tetra-
cobalt complexes (i.e., 2). We have developed an interest in
(20% yield).‡ The observation of Na+ and K+ ion adducts (m/z
1803 and 1819, respectively) in the electrospray mass spectrum
of this compound was central to the assignment as 5a. No
evidence of the smaller cyclophanediyne complex 6 could be
detected.
The reaction chemistry between 3a and 1,2,3-trimethox-
ybenzene was studied, and afforded similar results. Under the
analogous 5 3 1022 M reaction conditions, diarylation product
4b resulted (89% yield). Under the high dilution conditions,
cyclophanetetrayne complex 5b was the major isolated product
(15% yield).
The possibility of decomplexation of cyclophanetetrayne 5a
has been investigated. Reaction with an excess of Me3NO
(acetone, 0 °C, 1 h) gave metal-free cyclophanetetrayne 7 in
62% yield.
systems containing an aryl group as a spacer between propargyl
cation units,14 and as a result have begun investigation of the
Nicholas reaction chemistry of bis(propargyl acetate) complex
3a with electron rich arenes.
Compound 3a was readily accessible by complexation of
3b15 with Co2(CO)8 under standard reaction conditions (75%
yield). The bis(propargyl acetate) complex was then added to
1,3,5-trimethoxybenzene in the presence of BF3–OEt2. Reac-
tion was found to occur by one of two pathways, depending on
reagent stoichiometry and concentration. At 5 3 1022
M
concentration of 3a (CH2Cl2, 0 °C, 12 h), with an excess (4
The availability of the diarylated diyne complexes 4 afforded
an alternative possible route to the preparation of 5. Subjecting
4a to reaction with 1.0 equiv. of diacetate complex 3a (2 3 1023
† Electronic supplementary information (ESI) available: experimental
conditions and new compounds. See http://www.rsc.org/suppdata/cc/b2/
b203187f/
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This journal is © The Royal Society of Chemistry 2002

M, CH2Cl2, 0 °C, 12 h) in the presence of BF3–OEt2 (4 equiv.)
did successfully result in the formation of 5a (24% yield), along
with recovered 3a (31%) and 4a (31%). The analogous reaction
with 4b with 3a gave 5b (18% yield), with no recovered 3a or
4b.
Notes and references
‡ The use of 2.5 equiv of BF3–OEt2 gave 5a in lower (9–10%) yield.
§ Small amounts of 3a (15%) and 8 (17%) were also recovered.
¶ Dimethyl sulfonium adducts of propargyldicobalt cations are known to
regenerate the cations in solution via C–S bond cleavage.16 Propargyl ether
exchange reactions must involve reversible C–O bond cleavage.17
∑ The reaction of 3a, 1,3,5-trimethoxybenzene, and BF3–OEt2 (1 equiv.
each) is unselective for monocondensation.
** The para-disubstituted aryl ring protons are isochronous in each case,
with the following chemical shifts: d (ppm); 3a, 7.43; 3b, 7.34; 4a, 7.44; 4b,
7.47; 5a, 7.21; 5b, 7.43; 7, 7.10; 9, 7.19.
This alternative cyclization procedure opened the possibility
for the synthesis of mixed cyclophanetetraynes. In order to
investigate the feasibility of such an approach, we employed
bis(propargyl ether) complex 113 and the diarylated diyne
complex 8, the latter prepared from 1 and 1,3,5-trimethoxy-
benzene in 82% yield under conditions analogous to 4a and 4b.
Compound 4a was then subjected to BF3–OEt2 mediated
reaction with diyne complex 1. Unfortunately, under a variety
of conditions, this reaction afforded only trace amounts of 9.
Conversely, the condensation of 8 and an equimolar amount of
3a was more successful. In the presence of Lewis acid Bu2BOTf
(2.5 equiv.) in CH2Cl2 (4 3 1023 M, 0 °C, 15 h) two main new
products could be isolated. The compound eluting second
proved to be the target mixed cyclophanetetrayne 9 (26% yield).
Preceding 9 chromatographically was cyclophanediyne com-
plex 213 (25% yield).§
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The formation of cyclophanediyne complex 2 is the result of
a retrograde Nicholas reaction of 8 followed by an intra-
molecular Nicholas reaction of putative cation 10 on the
remaining arene. The facility with which 2 is formed by
Nicholas reaction chemistry has been previously reported by
our group,13 but this is to our knowledge the first example of a
retro-Nicholas reaction involving the cleavage of a carbon–
carbon bond.¶ 16,17 We believe that its appearance in this case
stems from a combination of the high stability of propargyl
cation dicobalt complexes11 and the very electron rich nature of
the trimethoxyaryl unit.
4 D. L. An, T. Nakano, A. Orita and J. Otera, Angew. Chem., Int. Ed.,
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The cyclophanetetraynes 5 and 7 are to our knowledge the
first examples of the [3.3.3.3]m,p,m,p-cyclophanetetrayne ring
system. They may be seen as alkyne extended homologues of
7 For cyclophyne or dehydrobenzannulene cobalt complexes, see Ref. 3a
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1751.
the known [1.1.1.1]m,p,m,p-cyclophanes, which have been
termed ‘calix[4]arenoids’ by Finocchiaro.18 Their occurrence is
likely a consequence of the difficulty of formation of the
corresponding cyclophanediyne 6. MM3 (CAChe) calculations
reveal that a substantial (a = ca. 15 °) bending of the para-
disubstituted arene ring would be necessary to form 6. As a
result, 5, which requires no such bond angle deformations, is
instead formed either through dimerization of 11, the demon-
strated reaction of 3a with 4, or both.∑ Each of these
cyclophanetetraynes, including metal-free 7, give a single
resonance for their benzylic methylene protons, indicating any
fluxional processes are at their fast exchange limit; this is
consistent with the expected larger cavity relative to the
calix[4]arenoids. Each of 5a, 7, and 9 is also characterized by a
small but noticeable upfield shift in the 1H NMR spectrum for
the para-disubstituted aryl ring protons, which may be the result
of shielding by the other arene rings in each molecule.** This
effect is absent or minuscule for 5b.
13 R. Guo and J. R. Green, Chem. Commun., 1999, 2503; R. Guo and J. R.
Green, Synlett, 2000, 746.
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The pursuit of a deeper understanding of the conformational
properties of these molecules, and synthetic work towards
cyclophanetetraynes with other aromatic bridging groups, are in
progress and will be reported in due course.
We are grateful to NSERC (Canada) for research support.
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