Azatriquinane as a platform for tripodal metal complexes and calixiform scaffolds

Article abstract of DOI:10.1002/anie.201006470

A puckered platform: Azatriquinanes and azatriquinacenes are convex, rigid molecular scaffolds for constructing tripodal ligands and calix-like structures with a basic nitrogen site at the bottom of the cavity (see space-filling structure; blue N, green C

Full text of DOI:10.1002/anie.201006470

DOI: 10.1002/anie.201006470
Ligand Design
Azatriquinane as a Platform for Tripodal Metal Complexes and
Calixiform Scaffolds**
Martyn Jevric, Tao Zheng, Nabin K. Meher, James C. Fettinger, and Mark Mascal*
Azatriquinane 1 is a bowl-shaped tricycle featuring an apical,
acutely pyramidalized nitrogen.[1,2] The trefoil fusion of three
five-membered rings in 1 results in an averaged C3v-symmetric
platform, which presents the opportunity to build out from
the sites a to the nitrogen (C-1, 4, and 7) to position
substituents in an array with a conic focus. Herein, we report a
synthetic approach to substitution at these sites, leading both
to a novel, conformationally fixed tripodal ligand system and
calix-like derivatives with a basic nitrogen at the bottom of
the cavity.
Scheme 1. Reagents and conditions: a) H2CCHCH2SiMe3, AlCl3,
CH2Cl2, 16 h, 90%; b) Me3SiCCSiMe3, AlCl3, CH2Cl2, 10 h, 68%.
The centerpiece of this chemistry is perchloroazatriqui-
nacene 3, a synthetic precursor to the parent azatriquinacene
2. It can be produced in a single step and high yield by
photochemical chlorination of 1 with SO2Cl2, and is available
in multigram quantities.[1] The presence of doubly allylic a
chloroamine functions in 3 suggested the potential to
generate cationic intermediates which could alkylate elec-
tron-rich p systems. Thus, the Lewis acid catalyzed reaction of
3 with either allyltrimethylsilane or bis(trimethylsilyl)acetyl-
ene led to the corresponding triallyl 4 or triyne 5 derivatives in
good yields (Scheme 1). Although a number of opportunities
for further elaboration present themselves in 4 and 5, we were
first attracted to the prospect of applying the azatriquinane
framework as a scaffold for tripodal ligands. To this end, we
envisaged a threefold “click” reaction[3,4] with the alkyne
functions in 5 to give a tris(1,2,3-triazole) similar to the
Sharpless TBTA ligand,[5] but with the nitrogen sites preor-
ganized in a trigonal-pyramidal arrangement. This was
accomplished as shown in Scheme 2. Desilylation of 5 with
fluoride gave 6, and subsequent dehalogenation with lithium
in tert-butanol gave triethynylazatriquinacene 7. Reaction of 7
with phenyl azide provided the tris(1,2,3-triazole) derivative
8, which could be hydrogenated to the ligand 9.
Simple mixing of 9 with either ZnII acetate or CoII acetate
in methanol gave rise to metal complexes, and X-ray quality
crystals of both could be obtained by capping the metals with
a terminal chloride ligand and exchanging the counterion for
PF6À. In each case, the coordination geometry is pseudo-
À
trigonal-bipyramidal, with the axial N M bond longer than
II
À
the equatorial N M bonds. For example, in the Co complex
(Figure 1), the former is 2.382(2) ꢀ and the latter are
2.012(2), 2.020(2), and 2.030(2) ꢀ. As noted above, an
attractive characteristic of this host is its degree of preorga-
nization, compared to flexible tris(2-aminoethyl)amine
(tren)-based ligands.[6,7]
The reaction of 3 with aromatic rings gave rise to triaryl-
substituted hexachloroazatriquinacenes 10 (Scheme 3). X-ray
[*] Dr. M. Jevric, Dr. T. Zheng, Dr. N. K. Meher, Dr. J. C. Fettinger,
Prof. M. Mascal
Department of Chemistry, University of California Davis
1 Shields Avenue, Davis, CA 95616 (USA)
E-mail: mascal@chem.ucdavis.edu
[**] This work was financially supported by National Science Foundation
grant CHE-0957798.
Figure 1. ORTEP[8] views of the X-ray crystal structure of the [9-
CoCl]PF6 complex (counterion omitted for clarity). Thermal ellipsoids
are drawn at the 60% probability level.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201006470.
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ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
717

Communications
Scheme 3. Reagents and conditions: a) RAr, AlCl3, CH2Cl2; b) Na,
iPrOH, THF; c) H2, Rh/Al2O3, EtOAc.
An unexpected but certainly inter-
esting outcome of the hydrogenation
reaction of 11a was the complete
saturation of the molecule to give
tricyclohexylazatriquinane 12a. This
occurred under the same conditions
as the reduction of 11b–d (5% Rh on
Al2O3, 1 atm H2), which otherwise gave
Scheme 2. Reagents and conditions: a) KF, MeOH, 16 h, 99%; b) Li,
tBuOH/THF, reflux, 1 h, 44%; c) PhN3, sodium ascorbate, CuSO4,
tBuOH/H2O, 808C, 6 h, 96%; d) H2, Pd/C, MeOH, 48 h, 98%.
crystal structures of these derivatives reveal them to be calix
shaped (Figure 2a). In order to take advantage of the basic
nitrogen site at the base of the cavity, the electron-with-
drawing chlorine substituents have to be removed. As above,
this could be accomplished by reduction with an active metal
to give azatriquinacenes 11. Likewise, these could also be
hydrogenated to the corresponding azatriquinanes 12. Inter-
estingly, in the case of 12c, the aromatic rings turn to occupy
the cavity in the solid state, probably due in part to weak
CArH···N hydrogen bonding with the now basic nitrogen
(Figure 2b).
the
expected
products
12b–d
(Scheme 3).
There is remarkably little in the way of prior work on
conformationally fixed amines with threefold symmetry to be
found in the literature. The only systems conceptually
analogous to 1,4,7-trisubstituted azatriquinanes are the cor-
respondingly substituted 1-azaadamantanes or quinuclidines.
Although none of the former have been described, Canary[9]
and Corey[10] have both published work on the latter. In these
papers, the main point is the chirality of the ring framework,
an issue that does not have to be confronted in the synthesis of
substituted analogues of 1 and 2 since the a-positions do not
become chiral centers. For our part, we can introduce chiral
C3 symmetry into the system by the addition across the double
bonds of triallyltriquinacene 4. For example, treatment of 4
with m-chloroperbenzoic acid (MCPBA) gives a separable
mixture of the C3-symmetric tris-epoxide 13 and asymmetric
isomer 14 in good overall yield (Scheme 4).
In summary, we have described the application of the
azatriquinane ring system as a novel, rigid, threefold sym-
metric molecular scaffold, and demonstrate this by the
synthesis of a preorganized tripodal transition-metal host
Figure 2. ORTEP[8] views of the a) X-ray crystal structure of 10c; b) X-
ray crystal structure of 12c. Thermal ellipsoids are drawn at the 60%
probability level.
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Angew. Chem. Int. Ed. 2011, 50, 717 –719

molecular architecture that triallyl, triethynyl, and triaryl
azatriquinanes have to offer.
Received: October 15, 2010
Published online: December 17, 2010
Keywords: calixarenes · fused-ring systems · tripodal ligands ·
.
triquinacenes · triquinanes
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Scheme 4. Reagents and conditions: a) MCPBA, CHCl3, 24 h, 13
(24%), 14 (70%).
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and a series of triaryl derivatives with calix-like structures. We
look forward to investigating the diverse opportunities in
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