Diels-alder reactivity of binuclear complexes with calixarene-like structures

Article abstract of DOI:10.1002/anie.200500683

The regioselectivity of the Diels-Alder reaction between ω-substituted dienoates and unsymmetrical dienophiles can be strictly controlled by "calixarene-like" metal complexes of type A (see scheme). The reaction of the dienoate coligand in A with acrylonitrile leads to the exclusive formation of the regioisomer adduct I, which is in striking contrast to the low regioselectivity of the background reaction. (Chemical Equation Presented).

Full text of DOI:10.1002/anie.200500683

Angewandte
Chemie
Synthetic Methods
DOI: 10.1002/anie.200500683
Diels–Alder Reactivity of Binuclear Complexes
with Calixarene-like Structures**
Steffen Käss, Thomas Gregor, and Berthold Kersting*
Dedicated to Professor Heinrich Vahrenkamp
on the occasion of his 65th birthday
The Diels–Alder reaction is one of the most useful reactions
in organic synthesis.[1] As a consequence, a large number of
strategies have been developed to control the course and rate
of this transformation.[2] Recently, it has been found that the
outcome of some cycloadditions can be altered remarkably
when performed inside the cavity of cyclodextrines,[3,4] self-
assembled molecular capsules,[5–7] or coordination cages.[8–10]
This fact intrigued us greatly and awoke our interest in the
Diels–Alder reactivity of the “calixarene-like” [M2(m-
L’)(L1)]+ complexes bearing unsaturated carboxylate coli-
gands L’ (Scheme 1).[11] We report herein the synthesis and
Scheme 1. Structures of H2L1 and its metal complexes. Compound
labels are given in Schemes 2–4. The cavity representation of the
complexes has been used for reasons of clarity. It should not be
confused with the one used for the cyclodextrins.
[*] S. Käss, T. Gregor, Prof. Dr. B. Kersting
Institut für Anorganische Chemie
Universität Leipzig
Johannisallee 29, 04103 Leipzig (Germany)
Fax: ( +49)341-973-6199
E-mail: b.kersting@uni-leipzig.de
[**] This work was supported by the Deutsche Forschungsgemeinschaft
(KE 585/3-1,2,3).
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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structures of a series of such complexes and demonstrate the
remarkable effect of the binding pocket on the regioselectiv-
ity of the Diels–Alder reaction between sorbinic acid and
acrylonitrile.
The observation that a,b-unsaturated carboxylate ligands
can be readily incorporated in the binding pocket of our
complexes[12] led us to focus our first investigation on the
Diels–Alder reaction between the cinnamate ion in 6 and 2,3-
dimethylbutadiene (2). The reaction between cinnamic acid 1
and 2 proceeds readily in solution with toluene at 1658C to
give the corresponding adduct 3 (Scheme 2).[13] However, the
reaction of 6 with a large excess of 2 in solution with toluene
did not occur, even when heated in a sealed glass tube at
2108C for 24 h.[14] The same behavior was observed for the
dizinc complex 7.
Figure 1. Structure of the dinickel complex 8, with thermal ellipsoids
drawn at the 30% probability level. Bond lengths and angles are given
in the Supporting Information.
sorbinic acid 10 and acrylonitrile 11 (Scheme 3). The reaction
of the free acid was investigated first. This reaction is rather
slow (pseudo first-order rate constant k’ = 4.8 ” 10ꢀ6 sꢀ1, t1/2
ꢁ 2 days) and produces a mixture of the four possible Diels–
Scheme 2. Preparation of 6–9.
It has been possible to synthesize the expected products 8
and 9 of the above reactions by substituting the bridging
chlorides in complexes 4 and 5 for triethylammonium
cinnamate (Scheme 2) and to determine the X-ray crystal
structure of complex 8 (Figure 1). This structure revealed the
presence of an unusual conformation of cyclohexene deriv-
ative 3, with both the phenyl and carboxylate residues in axial
positions. In general, the substituents in cyclohexene rings
assume equatorial positions.[15] The bisaxial arrangement in 8
is presumably enforced by the limited space in the binding
pocket, which can be described by the distances between
H38a···H33c (9.226 Š, diameter of the pocket) and C48···Ni1
(6.820 Š, depth of the pocket).[16] It is likely that these steric
constraints also inhibit the Diels–Alder reaction of the
coordinated cinnamate ion in 6.
The above findings prompted us to study a Diels–Alder
reaction between a coordinated dienoate ligand and an
external alkene. We chose to study the reaction between
Scheme 3. Preparation of 13a–15. Numbers in parentheses refer to the
yields of the isolated products.
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Chemie
Alder adducts 12a–d and the by-product 14. All acids 12a–d
isomerize under the basic reaction conditions to give the
corresponding a,b-unsaturated derivatives 13a–d. It was
possible to separate 13a, 13b, and 13d by fractional crystal-
lization and to determine their structures by 1H and 13C NMR
spectroscopic and X-ray crystallographic studies.[14] This
analysis confirmed unambiguously the assignment of the
regiochemistry as represented in Scheme 3. Complex 15
(prepared by a simple coligand exchange reaction) served as
a reference compound.
Scheme 5. Directing and protecting effect of the binding cavity.
We then looked at the Diels–Alder reaction between the
coordinated dienoate ligand in 16 and acrylonitrile
(Scheme 4). Surprisingly, this reaction was already complete
Finally, to investigate the role played by the tert-butyl
substituents of (L1)2ꢀ, we investigated the reactivity of the
analogous complex [Zn2{(2E,4E)-hexa-2,4-dienoate}(L2)]+ 26
of macrocycle (L2)2ꢀ lacking tert-butyl groups (Scheme 6).
Scheme 4. Preparation of complexes 18a,b, 19a,b, Diels–Alder prod-
ucts 12a,b, and a,b-unsaturated acids 13a,b. Numbers in parentheses
refer to the yields of the isolated products.
after 56 hours (pseudo first-order rate constant k’ = 1.4 ”
10ꢀ5 sꢀ1, t1/2 ꢁ 0.5 days) and gave only two products 18a and
18b in nearly quantitative yield in a ratio of 57:43, as revealed
by NMRspectroscopy. The dinickel complex 17 behaved in a
similar manner, thus producing 19a and 19b. To establish the
structures of the coligands, 18a and 18b (or 19a and 19b)
were decomposed under mild acidic conditions. In both cases,
this gave the hydrochloride of the macrocycle (H2L1·6HCl), a
metal(ii) salt (M = Znii or Niii), and the free acids 12a and 12b.
The latter isomerized in the presence of a base to the a,b-
unsaturated derivatives 13a and 13b, respectively. This
approach proved the structures of 12a and 12b and their
complexes. Thus, in striking contrast to the low regioselectiv-
ity observed in the background reaction, the Diels–Alder
reaction between coordinated 10 and acrylonitrile proceeds
with strict “meta” regioselectivity. In addition, there are no
detectable by-products, such as 14.
Scheme 6. Structure of H2L2 and reactivity of its dizinc complex 26.
The reaction of 26 with acrylonitrile and the subsequent
decomposition of the intermediate complexes 27a,b pro-
duced the acids 12a,b as the sole reaction products again in a
similar 55:45 ratio. The pseudo first-order rate constant k’ was
determined to be 8.2 ” 10ꢀ6 sꢀ1 (t1/2 ꢁ 1 day). This rate is
slower than the reaction between 16 and acrylonitrile (t1/2
ꢁ 0.5 days), but still significantly faster than the background
reaction (t1/2 ꢁ 2 days). Thus, the tert-butyl substituents do not
affect the regiochemistry of this particular Diels–Alder
reaction, but they clearly increase its rate. The observed
trend is indicative of a small stabilization of the transition
This regioselectivity and the fact that the Diels–Alder
adducts 12a,b do not isomerize in the binding pocket of the
complexes can be attributed to the directing and protecting
effect of the binding cavity, as schematically represented in
Scheme 5.
state by hydrophobic effects (DDG° ꢁ 3 kJmolꢀ1; kc0 omplex
/
kb0 ackground = exp(DDG°/RT)). This result would be consistent
with our earlier observation that complexes bearing less polar
carboxylate anions have higher stability constants.[17]
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Communications
The Diels–Alder reactivity of “calixarene-like” metal
complexes supported by the ligands H2L1 and H2L2 has been
described. The reaction between the coordinated sorbinate
coligand and acrylonitrile is controlled by the binding cavity
of the complexes and is highly regioselective. The new
method is currently only applicable to dienes with anchoring
carboxylate groups, but expansion of this approach to a
general concept for the control of the regioselectivity of
Diels–Alder reactions between unsymmetrical dienes and
dienophiles appears to be in reach. We are currently probing
the possibility whether the rate of these transformations can
be enhanced by enlarging the binding pocket of the com-
plexes.
Received: February 23, 2005
Revised: October 4, 2005
Published online: November 22, 2005
Keywords: binuclear complexes · calixarenes ·
.
Diels–Alder reaction · regioselectivity · synthetic methods
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-264278 (13d), -264279 (15·BPh4·EtOH), -264280 (16·BPh4), and
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