Practical approach to structurally diverse monoimine salts and nonsymmetrical metallosalphen complexes

Article abstract of DOI:10.1021/ol101898y

A practical approach toward the synthesis of monoimine NBu₄ salts derived from Zn(salphen) complexes is described. The method involves nucleophilic addition of the hydroxide anion to the imine bond followed by hydrolysis. These monoimines provide accessible and useful reagents for the synthesis of (chiral) metallosalens with fine-tunable properties.

Full text of DOI:10.1021/ol101898y

ORGANIC
LETTERS
2010
Vol. 12, No. 20
4592-4595
Practical Approach to Structurally
Diverse Monoimine Salts and
Nonsymmetrical Metallosalphen
Complexes
Eduardo C. Escudero-Ada´n,† Marta Mart´ınez Belmonte,† Jordi Benet-Buchholz,†
and Arjan W. Kleij*,†,‡
Institute of Chemical Research of Catalonia (ICIQ), AV. Pa¨ısos Catalans 16,
43007 Tarragona, Spain, and Institucio´ Catalana de Recerca i Estudis AVanc¸ats
(ICREA), Pg. Llu´ıs Companys 23, 08010 Barcelona, Spain
akleij@iciq.es
Received August 12, 2010
ABSTRACT
A practical approach toward the synthesis of monoimine NBu4 salts derived from Zn(salphen) complexes is described. The method involves
nucleophilic addition of the hydroxide anion to the imine bond followed by hydrolysis. These monoimines provide accessible and useful
reagents for the synthesis of (chiral) metallosalens with fine-tunable properties.
Salen complexes are widely applied as versatile catalyst
systems1 and components of materials with interesting
supramolecular and photophysical properties.2 These proper-
ties may be altered by changing the substitution pattern on
the aromatic rings of the (symmetrical) salen ligand, thereby
creating options to fine tune electronic and steric effects.3
Another less utilized route departs from desymmetrization
of the salen structure by introduction of different groups on
both salicylideneimine fragments.4 This latter strategy is
complicated by the difficulty to induce high selectivity when
the diamine reagent is treated with two separate salicylal-
dehydes and usually gives a mixture of products that need
to be separated by chromatographic methods.5 In the past
decade, various methods have been reported that focus on
the selective formation of nonsymmetrical salen ligands/
complexes.6 One of these methods involves monoimine
formation from diamine reagents by choosing appropriate
† ICIQ.
‡ ICREA.
(1) (a) Cozzi, P. G. Chem. Soc. ReV. 2004, 33, 410. (b) Baleiza˜o, C.;
Garcia, H. Chem. ReV. 2006, 106, 3987. (c) Darensbourg, D. J. Chem. ReV.
2007, 107, 2388. (d) Katsuki, T. Chem. Soc. ReV. 2004, 33, 437.
(2) (a) Wezenberg, S. J.; Kleij, A. W. Angew. Chem., Int. Ed. 2008, 47,
2354. (b) Akine, S.; Nabeshima, T. Dalton Trans. 2009, 10395. (c) Kleij,
A. W. Dalton Trans. 2009, 4635. (d) Leung, A. C. W.; MacLachlan, M. J.
J. Inorg. Organomet. Polym. Mater. 2007, 17, 57. (e) Kleij, A. W.
Chem.sEur. J. 2008, 14, 10520. (f) Cametti, M.; Nissinen, M.; Dalla Cort,
A.; Mandolini, L.; Rissanen, K. J. Am. Chem. Soc. 2005, 127, 3831.
(3) Larrow, J. F.; Jacobsen, E. N.; Gao, Y.; Hong, Y.; Nie, X.; Zepp,
C. M. J. Org. Chem. 1994, 59, 1939.
(4) For a recent review, see: Kleij, A. W. Eur. J. Inorg. Chem. 2009,
193.
(5) For a demonstrative example see: Konsler, R. G.; Karl, J.; Jacobsen,
E. N. J. Am. Chem. Soc. 1998, 120, 10780.
(6) Illustrative examples include: (a) Holbach, M.; Zheng, X.; Burd, C.;
Jones, C. W.; Weck, M. J. Org. Chem. 2006, 71, 2903. (b) Renehan, M. F.;
Schanz, H.-J.; McGarrigle, E. M.; Dalton, C. T.; Daly, A. M.; Gilheany,
D. G. J. Mol. Catal. A: Chem. 2005, 231, 205. (c) Campbell, E. J.; Nguyen,
S. T. Tetrahedron Lett. 2001, 42, 1221.
10.1021/ol101898y  2010 American Chemical Society
Published on Web 09/16/2010

reaction stoichiometries and conditions to allow selective
crystallization of the monoimine product from solution.7
These monoimines can, in a second metal-templated con-
densation step, give easy access to nonsymmetrical com-
plexes without scrambling of the imine bonds.8 However,
monoimine reagents with electron-withdrawing substituents
are still difficult to prepare since the corresponding bis-Schiff
base products cocrystallize with the desired monoimine,
making isolation a tedious process. We recently set out to
explore the synthesis of these electron-poor imines and report
here a general method that allows easy formation of these
reagents under very mild conditions. These compounds create
new and extended possibilities for the electronic and steric
fine-tuning of new push-pull systems,9 salen complexes with
predesigned electronic features to accommodate or improve
catalytic conversions,10 and new, conjugated macromolecular
salen compounds.11
CH3CN immediately provoked full dissolution of the solid
material, and concomitantly a strong color change from
orange to deep red was observed. After simple workup of
the crude mixture (see Supporting Information), a crystalline
red solid was isolated.
1
These crystals were first analyzed by H NMR (DMSO-
d6) and revealed the presence of a product with a charac-
teristic peak at 4.95 ppm (NH2 group) and four distinct
resonances that can be ascribed to a NBu fragment. X-ray
diffraction then unambiguously determined the nature of this
product, and the result is reported in Figure 1.14 The structure
Our initial focus was on Zn(salphen) complex 1a (Scheme
1, salphen ) N,N′-bis[salicylideneimine]-1,2-phenylenedi-
Scheme 1
.
Nucleophilic Addition of NBu4OH to Zn(salphen) 1a
Giving Monoimine NBu4 Salt 1b
Figure 1. X-ray molecular structure of monoimine NBu4 salt 1b.
H-atoms are omitted for clarity. Please note that the phenolic
O-atom (O3) is anionic.
comprises a monoimine salt (the phenolic position is depro-
tonated) with a NBu4 counterion. In line with the NMR data,
a “free” amine is present which should be the result of the
hydrolysis of one of the imine bonds in 1a. Upon analysis
of the crude reaction mixture, we found further evidence for
this assumption since the presence of 3-nitro-salicylaldehyde
was confirmed by comparing the NMR characteristics with
those of an authentic sample. It is therefore reasonable to
consider a mechanism where nucleophilic addition of the
OH anion to the imine bond15,16 is mediated by initial OH
coordination to 1a.13 This produces a homogeneous reaction
mixture following addition of another OH anion with
subsequent proton abstraction from (adventitious) water
present in the medium. To further confirm that the OH anion
amine) which was treated with a methanolic solution of
NBu4OH (1 M) in CH3CN at room temperature; we
hypothesized that nucleophilic attack of the OH anion on
the imine bond should allow for imine hydrolysis. It should
be noted that complex 1a, as for most of the Zn(salphen)
complexes in this work, is virtually insoluble in CH3CN as
a result of strong self-dimerization and π-π stacking
interactions.12 We recently reported that the axial position
in the Zn(salphen) complex can be coordinated by various
anions giving rise to stable assembled structures.13 In the
present case, addition of NBu4OH to a suspension of 1a in
(7) (a) Mun˜oz-Herna´ndez, M.-A.; Keizer, T. S.; Parkin, S.; Patrick, B.;
Atwood, D. A. Organometallics 2000, 19, 4416. (b) Kleij, A. W.; Tooke,
D. M.; Lutz, M.; Spek, A. L.; Reek, J. N. H. Eur. J. Inorg. Chem. 2005,
4626. (c) Curreli, S.; Escudero-Ada´n, E. C.; Benet-Buchholz, J.; Kleij, A. W.
J. Org. Chem. 2007, 72, 7018. (d) Dalla Cort, A.; Mandolini, L.; Palmieri,
G.; Pasquini, C.; Schiaffino, L. Chem. Commun. 2003, 2178.
(8) (a) Curreli, S.; Escudero-Ada´n, E. C.; Benet-Buchholz, J.; Kleij,
A. W. Eur. J. Inorg. Chem. 2008, 2863. (b) Castilla, A. M.; Curreli, S.;
Carretero, N. M.; Escudero-Ada´n, E. C.; Benet-Buchholz, J.; Kleij, A. W.
Eur. J. Inorg. Chem. 2009, 2467. (c) Castilla, A. M.; Curreli, S.; Mart´ınez
Belmonte, M.; Escudero-Ada´n, E. C.; Benet-Buchholz, J.; Kleij, A. W. Org.
Lett. 2009, 11, 5218.
(12) Zinc-based salphen complexes with groups that are sterically not
sufficiently large enough give rise to dimer formation through µ-oxo bridges
where one O-atom of each salphen ligand acts as an axial ligand. For recent
work on this subject: (a) Mart´ınez Belmonte, M.; Wezenberg, S. J.; Haak,
R. M.; Anselmo, D.; Escudero-Ada´n, E. C.; Benet-Buchholz, J.; Kleij, A. W.
Dalton Trans. 2010, 39, 4541. (b) Elemans, J. A. A. W.; Wezenberg, S. J.;
Escudero-Ada´n, E. C.; Benet-Buchholz, J.; den Boer, D.; Coenen, M. J. J.;
Speller, S.; Kleij, A. W.; De Feyter, S. Chem. Commun. 2010, 46, 2548.
(13) Wezenberg, S. J.; Escudero-Ada´n, E. C.; Benet-Buchholz, J.; Kleij,
A. W. Chem.sEur. J. 2009, 15, 5695.
(9) Rigamonti, L.; Demartin, F.; Forni, A.; Righetto, S.; Pasini, A. Inorg.
Chem. 2006, 45, 10976.
(10) For examples of Zn(salphen)-mediated catalysis: (a) Zelder, F. H.;
Rebek, J., Jr. Chem. Commun. 2006, 753. (b) Decortes, A.; Mart´ınez
Belmonte, M.; Benet-Buchholz, J.; Kleij, A. W. Chem. Commun 2010, 46,
4580.
(14) Crystallographic summary: Formula C29H46N4O3, Fw 498.70,
orthorhombic, Pna2(1), a ) 16.092 Å, b ) 13.971 Å, c ) 12.527 Å, a )
b ) g ) 90°, V ) 2816.3 Å3, Z ) 4, rcalc ) 1.176 mg/M3, F(000) ) 1088,
θ (min/max) ) 1.9/32.3°, total reflections ) 6612, unique ) 5796 (Rint
)
(11) (a) Gallant, A. J.; MacLachlan, M. J. Angew. Chem., Int. Ed. 2003,
42, 5307. (b) Frischmann, P. D.; Jiang, J.; Hui, J. K.-H.; Grzybowski, J. J.;
MacLachlan, M. J. Org. Lett. 2008, 10, 1255.
0.050), GoF ) 1.021, R1/wR1 ) 0.0458/0.1132 [I > 2s(I)], R1/wR1 )
0.0542/0.1197 (all data), flack parameter ) -0.7(9), res. electr. dens. 0.342
and -0.239 e·Å-3
.
Org. Lett., Vol. 12, No. 20, 2010
4593

plays a dominant role in this conversion, complex 1a was
also treated under similar conditions with NaOH in a separate
reaction. Although a heterogeneous mixture was retained, a
clear color change from orange to red (as in the reaction
with NBu4OH) was observed for the reaction mixture.
Table 1. Synthesis of Monoimine NBu4 Salts 1b-12b Using
Complexes 1a-12aa
1
Analysis of the solid material by H NMR revealed the
presence of both the monoimine product (presumably as the
sodium salt) as well as the liberated salicylaldehyde. Hence,
the use of NBu4OH is clearly advantageous as it gives rise
to a homogeneous mixture and facilitates product isolation
by means of crystallization (Supporting Information).
The scope of this new protocol was then tested with a
series of Zn(salphen) complexes having various (electron-
withdrawing) peripheral groups (i.e., 1a-12a, Scheme 1).
We were delighted to find that monoimine salts 1b-12b
could be readily obtained. In all cases, the monoimine NBu4
salts were produced in moderate to good yields (Table 1);
the ionic nature was easily revealed by ESI(-)-MS; and the
structures of 2b and 10b were also supported by X-ray
diffraction studies (Supporting Information). Notably, com-
pounds 1b-12b were produced under very mild conditions
(rt, CH3N as medium) and very short reaction times (e5-10
min). Although the reaction works very efficiently with those
Zn complexes having electron-withdrawing groups, we found
that Zn(salphens) having donating groups (Table 1, entry 8)
can also be converted into the monoimine salt. Interestingly,
when nonsymmetrical Zn(salphen)s were utilized (Table 1,
entries 4, 9, and 10), high selectivity was observed for
breaking of only one of the two imine bonds.17 While for
compounds 4b and 9b the isolated materials showed virtually
entry
product
R1
R2
X
Y
yield (%)b
1
2
3
4
5
6
7
8
1b
2b
3b
4b
5b
6b
7b
8b
9b
H
H
Cl
Cl
Cl
Br
H
tBu
Br
Br
NO2
H
NO2
NO2
Cl
Cl
Cl
H
Br
H
H
H
H
Cl
H
NO2
Cl
Cl
Cl
H
H
Cl
H
51
58
40
49
76
59
67
44
53
41
55
8
c
c
H
1
a single compound in the H NMR spectra, for 10b two
Cl
Cl
Cl
H
isomeric structures were observed in an approximate 7:3 ratio
(Supporting Information). We also probed complex 12a since
it constitutes two imine bonds with potentially different
reactivity. Under the conditions used for the preparation of
1b-11b, we found that no genuine selectivity could be
observed for scission of only one of the imine bonds. A small
amount of pure 12b (8%) was isolated, but subsequent
fractions of product that were collected contained both
possible monoimine derivatives. Apparently, complex 12a
is hydrolyzed at both imine bonds under these experimental
conditions, and cocrystallization prevents isolation of either
product in high yield.
9
NO2
H
H
H
Brc d
H
,
10
11
12
10b
11b
12b
NO2
Br
H
H
a All reactions carried out on a 0.24-0.40 mmol scale based on the
Zn(salphen) except for entries 1 (0.61 mmol) and 8 (0.83 mmol). b Isolated
yield. c Structure supported by NMR predictive simulations using gNMR
from IvorySoft and 1H-COSY measurements. d Structure of the major
isomer supported by X-ray crystallography; see Supporting Information.
We then used monoimine salts 1b and 5b as reagents for
metallosalen structures that are not (easily) accessible through
the known synthetic routes (Scheme 2). Thus, treatment of
1b/5b with a (substituted) salicylaldehyde and metal acetate
in a one-pot procedure7b gave access to metallosalen
structures 13-15. The synthesis of the Zn(salphen) complex
14 represents an example of a desymmetrization protocol
where first the symmetrical complex 1a is converted into
monoimine salt 1b followed by a condensation step that
allows for the presence of different ring substituents in the
second aldimine fragment. We then also focused on the
preparation of chiral metallosalens (16 and 17) using a known
binaphthyl-based dialdehyde (Supporting Information).18
These types of bismetallosalen derivatives have recently
attracted much attention in the polymerization of ep-
oxides.19 Compounds 16 and 17 were easily prepared
(15) Similar nucleophilic additions to imine bonds in metallosalen
structures have been reported: (a) Cametti, M.; Dalla Cort, A.; Colapietro,
M.; Portalone, G.; Russo, L.; Rissanen, K. Inorg. Chem. 2007, 46, 9057.
(b) Wang, Y.; Parkin, S.; Atwood, D. Inorg. Chem. 2002, 41, 558. (c) Paris,
¨
S. I. M.; Laskay, U.; Liang, S.; Pavlyuk, O.; Tschirschwitz, S.; Lo¨nnecke,
(18) Belokon, Y. N.; Chusov, D.; Borkin, D. A.; Yashkina, L. V.;
Bolotov, P.; Skrupskaya, T.; North, M. Tetrahedron: Asymmetry 2008, 19,
459.
¨
¨
¨
P.; McMills, U. C.; Jackson, U. P.; Petersen, U. L.; Hey-Hawkins, E.; Jensen,
U. P. Inorg. Chim. Acta 2010, doi: 10.1016/j.ica.2010.06.041.
¨
(16) Note that the use of NBu4X (X ) Cl, I) did not provoke hydrolysis
of the imine bond in 1; in these cases, unreacted 1 was isolated as the only
product.
(19) (a) Hirahata, W.; Thomas, R. M.; Lobkovsky, E. B.; Coates, G. W.
J. Am. Chem. Soc. 2008, 130, 17658. (b) Widger, P. C. B.; Ahmed, S. M.;
Hirahata, W.; Thomas, R. M.; Lobkovsky, E. B.; Coates, G. W. Chem.
Commun. 2010, 46, 2935.
(17) Note that this is the case for the isolated product.
4594
Org. Lett., Vol. 12, No. 20, 2010

of a highly Lewis acidic Zn center20 that increases the
reactivity of the imine bond.21 The reported protocol is
advantageous in terms of reaction conditions, isolation, and
scope using easily accessible Zn(salphen) complexes as
substrates. These monoimine salts are not (easily) accessible
via other methods and thus create new potential for the fine-
tuning of steric and electronic features of metallosalen
structures (cf., Scheme 2) useful in various applications
including homogeneous catalysis and as molecular building
blocks in supramolecular chemistry.22 Our future plans focus
on the application of this new reactivity for the fabrication
of larger, multinuclear metallosalen architectures.
Scheme 2. Synthesis of Nonsymmetrical Metallosalen
Complexes 13-17 Using Monoimine Salt 1b and 5b as
Reagents
Acknowledgment. We thank ICIQ (ECE, MMB, JB, and
AWK), ICREA (AWK), the Ministereo de Ciencia e Inno-
vacio´n (MICINN, project CTQ-2008-02050/BQU, AWK),
Consolider Ingenio 2010 (project CSD2006-0003, AWK),
and the COST-D40 action (AWK) for support. Dr. Noem´ı
Cabello and Alba Gonzalez are thanked for the mass
spectrometric studies. Daniele Anselmo is thanked for
providing the chiral bisaldehyde used for the synthesis of
16 and 17.
Supporting Information Available: Synthetic and com-
plete analytical data for all new compounds, copies of NMR
spectra, and crystallographic data for 1b, 2b, and 10b in CIF
format. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL101898Y
(20) For recent contributions demonstrating the high Lewis acid character
of the Zn ion in these salphen complexes, see: (a) San Felices, L.; Escudero-
Ada´n, E. C.; Benet-Buchholz, J.; Kleij, A. W. Inorg. Chem. 2009, 48, 846.
(b) Mart´ınez Belmonte, M.; Escudero-Ada´n, E. C.; Benet-Buchholz, J.; Kleij,
A. W. Eur. J. Inorg. Chem. 2009, 5307. (c) Escudero-Ada´n, E. C.; Benet-
Buchholz, J.; Kleij, A. W. Eur. J. Inorg. Chem. 2009, 3562.
using monoamine 1b, and simple variation of the elec-
tronic features in these structures through the use of
different monoimine reagents can thus provide a new
series of (polymerization) catalysts.10b,19
In summary, we described a new, mild, and easy method
for the synthesis of a series of monoimine salts derived from
Zn-centered salphen complexes. This new methodology is
based on a selective imine bond hydrolysis provoked by
addition of an OH nucleophile. The nucleophilic addition
of the hydroxide anion is likely facilitated by the presence
(21) We also examined the use of the chiral Zn complex based on N,N′-
bis[3,5-di-tert-butylsalicylidene-1,2-diaminocyclohexane] and a nonmeta-
lated salphen ligand as substrates: in the first case, no reaction was observed,
while in the latter case, only some hydrolysis was noted in the isolated,
impure product. See for details the Supporting Information. The results imply
the importance of the presence of a salphen backbone in combination with
Zn to have sufficient reactivity/selectivity.
(22) For a recent example: Wezenberg, S. J.; Escudero-Ada´n, E. C.;
Benet-Buchholz, J.; Kleij, A. W. Inorg. Chem. 2008, 47, 2925.
Org. Lett., Vol. 12, No. 20, 2010
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