Manganese amido-imine bisphenol Hangman complexes

Article abstract of DOI:10.1016/j.tetlet.2008.05.111

A modular ligand macrocycle is composed from two phenolic groups linked to a cyclohexane bridge through an amide bond and an imine bond. The stability of the asymmetric linkers to metathesis permits a macrocyclic platform to be assembled from the condensation of two different phenolic groups in a single-step, high yield, reaction. The primary coordination sphere may be tuned with functional groups on one phenolic group. The other phenolic group may be modified with a scaffold possessing a proton transfer group. In this way, control over the secondary coordination sphere of the macrocycle is achieved. Manganese complexes of the amido-imine linked macrocycle catalytically epoxidizes 1,2-dihydronapthalene using sodium hypochlorite as the oxidant. The amido-imine macrocycles represent a new metal active site capable of supporting high oxidation states and attendant atom transfer chemistry while at the same time permitting control over the primary and secondary sphere of the metal center.

Full text of DOI:10.1016/j.tetlet.2008.05.111

Tetrahedron Letters 49 (2008) 4796–4798
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Tetrahedron Letters
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Manganese amido-imine bisphenol Hangman complexes
*
Jenny Y. Yang, Daniel G. Nocera
Department of Chemistry, 6-335, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139-4301, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 24 December 2007
Revised 2 May 2008
Accepted 5 May 2008
Available online 14 June 2008
A modular ligand macrocycle is composed from two phenolic groups linked to a cyclohexane bridge
through an amide bond and an imine bond. The stability of the asymmetric linkers to metathesis permits
a macrocyclic platform to be assembled from the condensation of two different phenolic groups in a sin-
gle-step, high yield, reaction. The primary coordination sphere may be tuned with functional groups on
one phenolic group. The other phenolic group may be modified with a scaffold possessing a proton trans-
fer group. In this way, control over the secondary coordination sphere of the macrocycle is achieved.
Manganese complexes of the amido-imine linked macrocycle catalytically epoxidizes 1,2-dihydronaptha-
lene using sodium hypochlorite as the oxidant. The amido-imine macrocycles represent a new metal
active site capable of supporting high oxidation states and attendant atom transfer chemistry while at
the same time permitting control over the primary and secondary sphere of the metal center.
Ó 2008 Elsevier Ltd. All rights reserved.
Manganese Schiff-base Hangman complexes shown in Chart
11–3 activate O–O bonds by mechanisms involving proton-coupled
electron transfer (PCET).4–8 The Hangman ligand architecture
comprises a macrocyclic ligand platform appended to a scaffold
possessing a proton transfer group, PTG (HSX in Chart 1). The
PTG is poised over the macrocyclic ligand so the redox activation
of substrate bound to the metal center can be mediated by proton
transfer. The O–O bond heterolysis is promoted within the
Hangman cleft by the same ‘pull effect’ that is common to oxida-
tion conversions promoted at heme cofactors.9 The original HSX
design appended the PTG to the bridge of the salen platform. In this
configuration, the redox potential is easily tuned by modifying the
functionalities para to the phenolic oxygens.1 However, this point
of attachment obviates the incorporation of the chiral functionality
that is a mainstay of reactivity for this ligand class.10 Alternatively,
the scaffold may be moved to the position para to the phenolic
oxygens so that the chiral functionality, such as the cyclohexanedi-
amine bridge of HSXÃ, may be retained at the salen platform.2,3
However, owing to facile hydrolysis of the imine bond even under
very mild conditions (vide infra),11 an asymmetric Hangman plat-
form with a single scaffold is difficult to prepare. Hence, only the
double bridge Hangman complex shown in Chart 1 is available.
This double-scaffold design has two drawbacks with regard to
elaborating PCET activation chemistry. (1) The easiest position
(para position to the phenolic oxygen) at which to tune the redox
properties of the macrocyclic platform is unavailable because it is
occupied by the scaffold and (2) protons from the convergent inter-
faces may interact; in the case of PTG = benzoic acid, a dicarboxylic
acid dimer is obtained.2 Hence the proton needed for PCET reactiv-
ity is engaged in the dimer and unavailable for interaction with
bound substrate.
We attempted to synthesize ligand A, shown in Chart 1, where
one of the xanthenes is removed to open a site where electron-
donating and withdrawing functionalities, –X, can be installed to
tune the redox properties. However, isolated salen ligands that
are asymmetric across their diamine bridge are rare (i.e., composed
of two unique salicylaldehydes),12–15 and when prepared are often
contaminated by the symmetric impurity owing to the facility at
which imine hydrolysis occurs.12,13 This hydrolysis problem has
been overcome by the incorporation of an ethylene diether back-
bone to bridge the functionalized phenolic arms of the ligand.
The equilibrium constant for the formation of the oxime is larger
than that of the imine by several orders of magnitude.11 Thus,
the oxime-type ligand is able to resist metathesis of the C@N
bonds. In this Letter, we propose an alternative modification of
the basic salen framework in which one of the imine bonds is
replaced by an amido bond (B in Chart 1), which is less prone to
hydrolysis. The synthesis of macrocyclic ‘half-units’ are targeted
where a cyclohexanediamine is singly condensed to form an amido
bond, leaving the other amine available to form an imine bond. In
stabilizing the macrocycle in this way, Hangman salen-based plat-
forms may be derivatized by a single Hangman platform so that the
electronic properties of the salen platform may be tuned and the
stereogenic centers of the salen scaffold may be unperturbed.
The step-wise synthesis of scaffold B is outlined in Scheme 1 for
a 3-tert-butyl salicylaldehyde functionalized with tert-butyl (5),
methoxy (8), bromo (9), and nitro (10) in the 5 position. 3,5-di-
tert-butyl salicylaldehyde and 3-tert-butyl salicylaldehyde were
obtained commercially. The methoxy,16 bromo,17 and nitro18 ana-
logues can all be prepared in one step.
* Corresponding author. Tel.: +1 617 253 5537; fax: +1 617 253 7670.
E-mail address: nocera@mit.edu (D. G. Nocera).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.05.111

J. Y. Yang, D. G. Nocera / Tetrahedron Letters 49 (2008) 4796–4798
4797
Chart 1.
Scheme 1. Reagents: (a) Ag2O, 3 M NaOHaq; (b) (1R,2R)-(À)-1,2-diaminocyclohexane, N-methylmorpholine, 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimineÁHCl, CH2Cl2;
or (i) SOCl2, (ii) (1R,2R)-(À)-1,2-diaminocyclohexane, Et3N, CH2Cl2; (c) 3,5-di-tert-butyl-2-hydroxybenzaldehyde, EtOH; (d) 2,7-di-tert-butyl-5-(3-formyl-4-hydroxy-phenyl)-
9,9-dimethyl-9H-xanthene-4-carboxylic acid, EtOH; (e) Mn(OAc)2(H2O)4, EtOH.
The aldehydes are oxidized to the corresponding carboxylic acid
to give the salicylic acid derivatives by heating with silver(I) oxide
in basic solution. Coupling proceeds with one equivalent of
(1R,2R)-(À)-1,2-diaminocyclohexane by either of two methods to
form the amide bond: 5 and 6 were synthesized in good yields
by allowing the acid and diamine to react with 1-[3-(dimethyl-
amino)propyl]-3-ethylcarbodiimineÁHCl and N-methylmorpholine;
7–10 were synthesized by allowing the acid to react with thionyl
chloride to form the acetyl chloride in situ, followed by addition
of the diamine. Both methods give small amounts of the symmetric
diamide ligand impurity despite dilute reaction conditions. The
symmetric diamido bisphenolate ligand can be separated from
products 5–10 by column chromatography. Macrocycle formation
is completed by condensation in refluxing ethanol of the free
amine with the appropriately functionalized salicylaldehyde to
form the imine bond, thus furnishing the amido-imine macro-

4798
J. Y. Yang, D. G. Nocera / Tetrahedron Letters 49 (2008) 4796–4798
cycles. NMR spectra of 11 and 13 show no evidence for functional
group redistribution. The NMR peaks of the phenolic groups of the
singly functionalized platform are maintained in the NMR spec-
trum (see Figs. S1 and S2). Manganese(III) ion insertion into 11
and 13 to give 12 and 14, respectively, proceeds smoothly upon
refluxing manganese(II) acetate tetrahydrate in ethanol in air.
The amido nitrogen is deprotonated during metalation to afford
the neutral complex.19 The molecular weights of the ions (sodium
adduct) obtained by high resolution mass spectrometry are consis-
tent with this formulation for the complex. Unique amide (C@O)
and imine (C@N) stretches are present in the infrared spectra.
The C@O stretch is observed at 1628 cmÀ1 in 11 and 1638 cmÀ1
in 13. In the manganese complexes, the stretching frequency shifts
to 1624 cmÀ1 in 12 and 1626 cmÀ1 in 14. The shift upon metalation
is more dramatic for the imine bond; the stretching frequency at
1587 cmÀ1 in 11 and 1588 cmÀ1 in 13 shifts to 1535 cmÀ1 and
1531 cmÀ1 in their respective manganese complexes.
We were interested in ascertaining how our substitution of an
amido group for an imine in Hangman platform would affect the
PCET reactivity. Accordingly, the epoxidation activity of 12 and
14 was examined using 1,2-dihydronapthalene as the substrate.
Sodium hypochlorite was used as the external oxidant, under the
same conditions previously used to study the double-scaffold
Hangman salen complexes.2,3 12 and 14 support the catalytic oxi-
dation of 1,2-dihydronapthalene to the corresponding epoxide
with 32% and 28% yield, respectively. We note however, despite
the presence of the (1R,2R)-(À)-1,2-diaminocyclohexane backbone,
the epoxide product isolated is a racemic mixture. The lack of
asymmetric induction by these ligands may be due to the greater
flexibility afforded by an amido linker. In salens, the geometry of
the macrocycle in the Mn(V) oxo species is proposed to be roughly
planar.20 However, the analogous diamido macrocycles are known
to be more structurally flexible and they can deviate from a non-
planar coordination.21 If such conformational changes perturb
substrate approaches toward the oxidizing intermediate, then
communication with the chiral cyclohexane bridge may be
prevented.
Acknowledgments
We thank Professor Gregory Fu’s for the use of his chiral gas
chromatography and Shih-Yuan Liu for instrument assistance and
helpful discussion. This work was supported by funding from the
DOE DE-FG02-05ER15745.
Supplementary data
Full experimental details and characterization data for all new
compounds, including copies of 1H NMR spectra for 11 and 12.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2008.05.111.
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In summary, the trianionic amido-amine ligands permit a salen-
like ligand to be modified with a single Hangman scaffold. The
oxygen atom transfer chemistry performed by the manganese
complexes suggest they are capable of supporting a high-valent
metal oxo intermediate, consistent with the ability of diamido
diphenolic ligands ability to stabilize metals in high oxidation
states.22,23 The synthetic method to construct these ligands is
modular, thus allowing the electronic and redox properties of the
scaffold to be tuned with facility.
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