An iminoboronate construction set for subcomponent self-assembly

Article abstract of DOI:10.1002/chem.200800074

Recently we have demonstrated a series of systems in which complex structures were created from simple amine and aldehyde subcomponents by copper(I)-templated imine bond formation. We describe herein the extension of this subcomponent self-assembly concept to the generation of structures based upon the iminoboronate ester motif. Equimolar amounts of diol, amine, and 2-formylphenylboronic acid reacted by reversible B-O and C=N bond formation to generate iminoboronate esters, as has recently been reported by James et al. (Org. Lett. 2006, 8, 609-612). The extent of ester formation was shown to depend upon a number of factors. The exploration of these factors allowed rules and predictions to be formulated governing the self-assembly process. These rules allowed the construction of more complex structures containing multiple boron atoms, including a trigonal cage containing six boron centers, as well as pointing the way to the construction of yet more intricate architectures. The lability of the B-O and C=N bonds also allowed different diol and amine subcomponents to be substituted within these structures. Selection rules were also determined for these substitution reactions, allowing the products to be predicted based upon the electronic properties of the diols and diamines employed. These results thus demonstrate the generality of the subcomponent self-assembly methodology through its application to a new dynamic covalent system.

Full text of DOI:10.1002/chem.200800074

FULL PAPER
DOI: 10.1002/chem.200800074
An Iminoboronate Construction Set for Subcomponent Self-Assembly
Marie Hutin,[a] GØrald Bernardinelli,[b] and Jonathan R. Nitschke*[c]
Abstract: Recently we have demon-
strated a series of systems in which
complex structures were created from
simple amine and aldehyde subcompo-
nents by copper(I)-templated imine
bond formation.We describe herein
the extension of this “subcomponent
self-assembly” concept to the genera-
tion of structures based upon the imi-
noboronate ester motif.Equimolar
amounts of diol, amine, and 2-formyl-
phenylboronic acid reacted by reversi-
(Org. Lett. 2006, 8, 609–612).The
extent of ester formation was shown to
depend upon a number of factors.The
exploration of these factors allowed
rules and predictions to be formulated
governing the self-assembly process.
These rules allowed the construction of
more complex structures containing
ters, as well as pointing the way to the
construction of yet more intricate ar-
ꢀ
O
chitectures.The lability of the B
and C=N bonds also allowed different
diol and amine subcomponents to be
substituted within these structures.Se-
lection rules were also determined for
these substitution reactions, allowing
the products to be predicted based
upon the electronic properties of the
diols and diamines employed.These re-
sults thus demonstrate the generality of
the subcomponent self-assembly meth-
odology through its application to a
new dynamic covalent system.
multiple boron atoms, including
a
trigonal cage containing six boron cen-
Keywords: boronic esters · dynamic
covalent chemistry · imines · self-
assembly · template effects
ꢀ
ble B O and C=N bond formation to
generate iminoboronate esters, as has
recently been reported by James et al.
Introduction
ligands,[9] allowing the creation of complex structures from
simple building blocks.[10] Amine and aldehyde subcompo-
nents are brought together in a well-defined way within the
pseudo-tetrahedral coordination environment of the cop-
per(I) ion (Scheme 1a), creating a 908 angle between the
two imine ligands.This structure-directing bis(pyridylimine)-
copper(I) motif may be incorporated twice into the same
subcomponent if 2,9-diformyl-1,10-phenanthroline or 3,6-di-
formylpyridazine[11] is used, allowing the construction of
grids,[6,7] helicates,[7,12] macrocycles,[6,13] and a catenane.[14]
In the present work we describe the use of the iminoboro-
nate ester motif (Scheme 1b) in subcomponent self-assem-
bly.These esters have been developed recently by James
and co-workers as an elegant means of determining the
enantiopurity of amines[15] and diols.[16] This reaction is in-
herently multicomponent[4,17,18] in nature, uniting three dis-
tinct building blocks in a well-defined fashion: a diol sub-
component is held at 908 to an amine subcomponent around
a central pseudotetrahedral boron atom.
To build complex structures using self-assembly, it is neces-
sary to understand the rules governing the self-assembling
system: A deeper understanding of the rules governing a
system allows one to predict and create more complex struc-
tures, driving a conceptual shift[1] from serendipity[2] towards
rational design.[3,4]
Recently it has been demonstrated[5–7] that copper(I) may
serve as an excellent template[8] for the formation of imine
[a] Dr.M.Hutin
Department of Organic Chemistry
University of Geneva
30 Quai Ernest Ansermet, 1211 Gen›ve 4 (Switzerland)
[b] Dr.G.Bernardinelli
Laboratory of X-ray Crystallography
University of Geneva
24 Quai Ernest Ansermet, 1211 Gen›ve 4 (Switzerland)
[c] Dr.J.R.Nitschke
In expanding upon the examples presented by James
et al.,[15,16] we have investigated the scope and limitations of
Department of Chemistry, University of Cambridge
Lensfield Road Cambridge, CB2 1EW (UK)
Fax : (+44)1223-336017
this reaction, determining which diol and amine subcompo-
[19]
nents are mutually compatible.Multitopic
subcompo-
E-mail: jrn34@cam.ac.uk
nents, which bear multiple binding sites, may be used, allow-
ing the construction of assemblies containing two, three,
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
Chem. Eur. J. 2008, 14, 4585 – 4593
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4585

assemblies,[24] borylferrocene structures,[25] macrocycles,[26] as
well as self-repairing polymers[27] and porous networks.[28]
Results and Discussion
This study is divided into three parts.First, the rules govern-
ing the self-assembly and solution stability of a set of mono-
nuclear imino(boronate) esters from amine, diol, and 2-for-
A
mylphenylboronic acid were deciphered and explored.
Second, these rules were applied to the generation of more
complex structures, incorporating two, three, and four boron
centers, as well as a six-boron trigonal cage.The preparation
of these structures helped to illuminate the scope and limita-
tions of this reaction.Third, the rules governing the substitu-
tion of one subcomponent for another within these struc-
tures were investigated.Certain subcomponents were ob-
served to displace others cleanly; the observed selectivities
were analyzed in terms of the electronic properties of both
amine and diol subcomponents.
Scheme 1.Self-assembly of a) primary amine and 2-formylpyridine sub-
components with CuI to form a bis(pyridylimine)copper(I) complex, and
b) primary amine, 2-formylphenylboronic acid, and diol subcomponents
to form an imino(boronate) ester.
A
[20]
four, or six boron atoms.The dynamic covalent
nature of
Rules governing iminoboronate ester formation: To investi-
[21]
both B O and C=N bonds
allows both diol and amine
gate the scope and limitations of imino
(boronate) ester[29]
A
ꢀ
subcomponents to be independently displaced within these
structures in well-defined ways, allowing one structure to be
transformed into another.This work thus applies the con-
cepts of subcomponent self-assembly to the rich field of
boron-based self-assembly, which includes such recent exam-
ples as chemosensors,[22] multicomponent architectures,[18] re-
versibly formed cages,[23] boroxoaromatics,[21] anionic borate
formation in the context of subcomponent self-assembly, we
first prepared a series of mononuclear structures incorporat-
ing a variety of different diol and amine subcomponents.A
modified version of the procedure described by James
et al.[15,16] was employed: The reactions noted in Table 1
were carried out by mixing equimolar amounts of 2-formyl-
phenylboronic acid, diol, and amine in [D4]methanol.This
solvent was best able to dissolve the polyols investigated,
which showed poor solubility in nonpolar solvents.To avoid
possible competition between diol subcomponents and
methanol solvent (see below),[30] all samples were dried
under dynamic vacuum and all products were characterized
by NMR spectroscopy in CDCl3.
Five broad trends became apparent from the data pre-
sented in Table 1.First, charged amines did not form well-
defined, soluble iminoboronate esters with any of the three
diols.For positively charged 12 and negatively charged 10,
13, and 14, this appeared to be a result of the poor solubility
of the starting materials and products in chloroform and
methanol.
Abstract in French: Nous avons rØcemment obtenu plusieurs
structures complexes par la condensation dꢀamines et dꢀaldØ-
hydes en imines, grâce à lꢀaction template de cuivre(I). Nous
dØcrivons ici une extension de ce concept par la construction
de structures basØes sur le motif iminoboronate ester. Des
quantitØs Øquimolaires de diol, dꢀamine et dꢀacide 2-formyl-
phenylboronique rØagissent pour former des esters iminobo-
ꢀ
roniques contenant des liaisons rØversibles B O et C=N,
comme lꢀa rØcemment dØmontrØ Tony James (Org. Lett.
2006, 8, 609–612). La formation de ces esters dØpend dꢀun
certain nombre de facteurs. Leur analyse a conduit à lꢀØlabo-
ration des r›gles dirigeant cette rØaction dꢀautoassemblage.
Ces r›gles ont permis dꢀobtenir des architectures plus comple-
xes incorporant plusieurs centres boroniques, par exemple
Second, more electron-rich amines led to more complete
iminoboronate formation.We attribute this to the greater
nucleophilicity of more electron-rich imines, as has been ex-
plored in copper-templated systems.[31]
ꢀ
Third, catechol A produced more stable boronate esters
than the more electron-rich aliphatic diols B and C.We sus-
pect that this is a consequence of the greater Pauling elec-
tronegativity of hydrogen (2.2) than boron (2.0) and the
greater (resonance) stabilization of the catecholate dianion
than the ethylene glycolate dianion.Since a diolate residue
bound to an electropositive boron atom will have more
anionic character than the protonated diol, factors stabiliz-
ing the anion should also stabilize boron complexes.Ligand-
to-boron charge-transfer interactions from the more polariz-
une cage trigonale à six bores. La labilitØ des liaisons B O et
C=N permet à diffØrents sous-composants amine et aldØhyde
dꢀÞtre ØchangØs dans ces structures. Des r›gles de sØlection
ont Øgalement ØtØ dØterminØes pour ces rØactions de substitu-
tion, permettant de prØdire les produits obtenus sur la base
des propriØtØs Ølectroniques des diols et amines utilisØs. Ces
rØsultats dØmontrent la gØnØralitØ de la mØthodologie dꢀau-
toassemblage de sous-composants par son application à un
nouveau syst›me dynamique covalent.
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Dynamic Covalent Chemistry
FULL PAPER
plate[8] stabilization: Binding to a catecholate makes the
boron center more electron-deficient, thus rendering a
dative bond between nitrogen and boron more stabilizing to
the system as a whole.This mutual stabilization of ester and
imine moieties is reflected in Table 1: A high yield of one
condensation is strongly correlated with a high yield of the
other condensation.
Table 1.Amines and diols investigated in the iminoboronate-forming re-
action of Scheme 1b.[a]
A
B
C
Amine
Yield [%]
Yield [%]
Yield [%]
100
100
100
100
100
100
100
100
100
100
100
100
92
92
96
95
99
98
89
87
84
80
90
81
92
85
91
88
90
83
88
82
67
50
80
72
Fifth, among anilines and aliphatic diols, quantitative
ester formation is observed only in the case of p-toluidine 3
and ethylene glycol B.Electron-electron repulsion around
the boron center may result in destabilization in cases where
the highly electron-rich anilines 1 and 2 are present with
electron-rich diols B and C.
1
2
3
4
5
6
In a recent paper, Anslyn et al.investigated the structures
of a set of amino(boronate)ester compounds in solution and
G
in the solid state,[30] and were able to correlate 11B chemical
shifts with the coordination environments of boron centers.
Comparison of the 11B chemical shifts of selected com-
pounds from Table 1 with this prior work shed light upon
the coordination environments of the boron centers of this
series of compounds, which in turn helped to explain the ob-
served mutualism between imine and ester formation.
First, the 11B chemical shifts of 3A, 3B, and 3
(OMe)2
A
[33]
97
77
68
coincided at d=14.7 ppm in methanol, whereas they were
observed at d=15.1, 22.9, and 21.6 ppm, respectively, in
chloroform.This was consistent with the conclusion that
these diols did not compete effectively with the solvent in
methanol,[30] disfavoring the formation of their boronic
esters.
7
96
75
78
55
X
70
57
50
X
93
8
9
93
82
86
Second, in CDCl3 the 11B chemical shifts of 3
(OMe)2 and
G
Insol.Insol.Insol.
3B noted above were consistent with a trigonal-planar ge-
ometry at boron,[30] whereas the chemical shift of 3A sug-
gested a tetrahedral geometry in which a N!B bond was
present.Boron centers coordinated by alkoxides thus ap-
peared to be sufficiently electron-rich to gain no stabiliza-
tion by accepting a fourth, imine, ligand.Template stabiliza-
tion[8,9] would thus not be operative in these cases, which
could explain the lower yields associated with diols B and C.
10
11
100
100
100
100
100
100
Insol.Insol.Insol.
12
13
14
Insol.Insol.Insol.
Insol.Insol.Insol.
More complex structures via bridging subcomponents:
Having thus clarified the rules governing imino(boronate)
A
ester formation, we investigated how greater structural com-
plexity might be created by using this methodology.We rea-
soned that the use of multitopic[19] diol or amine subcompo-
nents, capable of bridging two or more boron centers, could
provide a route to more complex structures.
The use of bis(4-aminophenyl) ether 15 as a subcompo-
nent thus allowed construction of product 15A2, as shown in
Scheme 2a.As shown in Scheme 2b, pentaerythritol ( D)
provided a different geometry of ditopic linkage, joining two
[a] Yields [%] are given as determined by 1H NMR integration for the
products of imine condensation (in boldface) and boronic ester formation
(in italics) in CDCl3.Reactions that gave multiple unidentified products
are indicated by an “X”, and reactions that produced chloroform-insolu-
ble products are noted as “Insol.” Triethylamine (1 equiv) was added to
neutralize protonated amines 10, 12, 13 and 14.
able p system of the catecholate anion to the boron center,
in analogy to what is observed for d0 transition-metal cate-
cholates,[32] might also lend an additional degree of stabiliza-
tion to catechol boronate esters.
Fourth, the presence of a catechol (A) residue also en-
hanced imine formation, and the presence of a more elec-
tron-rich amine residue also stabilized the boronate ester.
This mutualistic effect may be explained in terms of tem-
imino(boronate) esters orthogonally by a central spiro-link-
A
age.[27] The initial use of methanol as a solvent, followed by
evaporation and NMR spectroscopic characterization of the
product in CDCl3, was undertaken to circumvent the very
low solubility of D in non-hydrogen-bonding solvents.
Compounds 15A2 and 112D were both synthesized quanti-
tatively; no aldehyde or free alcohol resonances were ob-
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J.R.Nitschke et al.
Scheme 3.Synthesis of compound 113E, of which only one possible con-
former is shown.
construction of macrocycles having well-defined geometries.
The product of the reaction of Scheme 4, in which 16 and D
were employed as subcomponents, was thus predicted to be
four-boron macrocycle 162D2.
Scheme 2.Preparation of di-boron structures a) 15A2 and b) 112D.
1
served in the H NMR spectra (see the Supporting Informa-
tion).The rules defined previously for mononuclear com-
pounds could thus be extrapolated to dinuclear compounds:
The formation of stable dinuclear iminoboronate ester 15A2
could be predicted based upon the successful participation
of subcomponents 2 and A (Table 1) in this condensation re-
action.The successful preparation of 112D could likewise be
predicted based upon the observation of the quantitative
formation of 11C.No diastereotopic splitting of the ethylene
protons of the 11 residues of 112D was observed, which was
consistent with a lack of N!B interactions and thus free ro-
Scheme 4.Formation of the macrocycle 162D2.
ꢀ
tation about the B C bonds.This lack of N !B interactions
was in turn consistent with the electron-rich character of D,
following the rules deciphered above.
Such a macrocycle was indeed observed experimentally.
When para-diaminobenzene 16, bis-diol D, and 2-formylphe-
nylboronic acid were heated in DMF at 508C overnight
(Scheme 4), crystals of the product 162D2 suitable for X-ray
analysis were obtained (Figure 1).Crystalline 162D2 dis-
played a very low solubility in all solvents tried, which pre-
cluded this productꢁs characterization by NMR spectroscopy.
NMR spectra of the crystallization supernatant showed a
complex mixture of products.The solubility of 162D2 was
sufficient, however, in a mixture of chloroform and THF to
allow its identification by APCI mass spectrometry.
To obtain more soluble macrocyclic products, several
other diamines[37] were investigated in concert with D as
subcomponents.NMR spectra in all cases indicated mixtures
of products.We suspect that the failures of these systems to
produce single macrocyclic products may be linked to the
poor ability of pentaerythritol D to form boronate esters:
Only aliphatic amine 11 quantitatively formed iminoboro-
nates with D or with its congener C.Furthermore, the fail-
ure of aliphatic diols to form boronate esters containing
Cyclotricatechylene-type molecules similar to E have
been employed as tritopic linkers in the generation of a vari-
ety of complex self-assembled architectures.[23,34] The reac-
tion of cyclotricatechylene E (1 equiv) with 2-formylphenyl-
boronic acid and amine 11 (3 equiv each) led to the forma-
tion of trinuclear 113E (Scheme 3).Again, the prior observa-
tion of 11A allowed us to predict that the structurally simi-
lar 113E would be stable.
When the sample was cooled, the NMR spectrum of 113E
showed features that we attributed to the presence of at
least three conformational isomers at low temperature.The
calculated[35] energetic barrier of about 60 kJmolꢀ1 for the
interconversion of these conformers was consistent with a
process involving rupture of the predicted N!B bond[36] fol-
ꢀ
lowed by free rotation about the B Cphenyl bond.A more in-
depth discussion of the low-temperature behavior of 113E is
presented in the Supporting Information.
Carrying this methodology further, we reasoned that the
use of rigid, difunctional subcomponents might allow the
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Dynamic Covalent Chemistry
FULL PAPER
Scheme 5.Formation of the cage 173E2; double-headed arrows indicate
key observed NOE correlations between protons
proposed structure is entirely consistent with MALDI-MS
and 2D-NMR measurements.ROESY 1H spectra were par-
ticularly instructive, showing NOE correlations (indicated
by arrows in Scheme 5) that were consistent with the indi-
cated high-symmetry cage structure.The successful prepara-
tion of 173E2 validated the use of iminoboronate subcompo-
nent self-assembly to generate well-defined, complex archi-
tectures based upon the rules detailed above, acting in con-
cert with the symmetries and numbers of linking functional
groups present in the starting subcomponents.[39]
Figure 1.Crystal structure of centrosymmetric macrocycle 162D2.
N!B bonds, as indicated by NMR spectroscopy (see
above) and crystallography (see below), deprives these as-
semblies of an important structure-determining element.
The resulting systems may possess too many degrees of free-
dom to be able to select a unique product from the diverse
dynamic combinatorial libraries[38] formed by the starting
subcomponents.
The crystal structure of 162D2 showed a centrosymmetric
macrocycle with trigonal-planar geometries for the boron
atoms, in accordance with our expectations for aliphatic al-
cohol D.Half of the nitrogen atomsꢁ lone pairs were direct-
ed away from the closest boron atoms, whereas the others
showed an N···B distance of 2.392(4) Š. This is substantially
longer than expected for a N!B coordinative interaction
(<1.75 Š).[30]
Subcomponent substitution reactions: Within structures con-
taining copper(I)-templated imine ligands it has been shown
that an electron-rich amine may displace a more electron-
poor amine residue.[31] The same driving force may be har-
nessed for substitution within imino(boronate)-containing
A
structures (Scheme 6), allowing the clean transformation of
one structure into another.
We therefore concluded that no template effect[8] was sta-
bilizing these imine bonds, in keeping with our NMR results
with aliphatic diols.We attribute thus the driving force for
the formation of this macrocycle to its lack of solubility in
the reaction mixture: the lack of imine templation would
lead to a lack of structural definition, resulting in the forma-
tion of a diverse mixture of cyclic and linear products in so-
lution, which is consistent with our NMR observations.
In contrast with aliphatic tetrol D, aromatic subcompo-
nent E might be expected to produce better-defined cage-
type[23] architectures due to the possibility of N!B coordi-
native interactions.This prediction was borne out by the
preparation of trigonal cage 173E2 (Scheme 5) upon mixing
cyclotricatechylene E with m-xylylenediamine 17 and 2-for-
mylphenylboronic acid in deuterated DMF under argon.
1
After one night at room temperature, H NMR spectroscopy
showed the clean formation of the cage 173E2.Although we
were not able to obtain X-ray quality crystals of 173E2, the
Scheme 6.Substitution reactions of amines 1 and 11 with iminoboronate
3A in CDCl3.
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J.R.Nitschke et al.
The addition of p-dimethylaminoaniline (1; 1 equiv) to a
chloroform solution of iminoboronate 3A (1 equiv) led to
the clean substitution of the p-toluidine residue of 3A,
giving 1A as the unique product.We attribute the driving
force of this reaction to the greater stabilization of the elec-
tron-poor boron center by the more electron-rich imine
ligand formed by subcomponent 1.[31]
Substitution was also observed when amine 11 (1 equiv)
was added to a chloroform solution of compound 3A
(1 equiv).The driving force of the reaction was again attrib-
uted to the formation of a more electron-donating, and thus
stabilizing, ligand in the case of aliphatic amine 11.In both
cases the substitution reaction was complete after 3 h at
room temperature, as determined by NMR monitoring.
In addition to their dynamic-covalent imine bonds, the
labile boron–oxygen bonds of iminoboronate esters may
serve as points of reassembly (Scheme 7).[21] Substitutions
carried out at these bonds may occur independently of sub-
stitutions involving the imine bonds: The two kinds of link-
ages are chemically orthogonal, allowing particularly rich
substitution chemistry.
than aliphatic diol esters: the partial negative charge on the
oxygen atoms in these esters is better stabilized by the pres-
ence of an aromatic ring.
Conclusion
The iminoboronate motif[15,16] thus serves as an excellent
tecton[41] for the creation of new architectures by subcompo-
nent self-assembly within the confines of the rules outlined
herein.A wide variety of structures are accessible, incorpo-
rating an extensive array of diol and amine subcomponents.
These building blocks may be multitopic,[19] allowing access
to architectures such as macrocycles and cages.Selective
substitution is possible within these structures at both diols
and amines, again following logical rules.This new set of
subcomponents includes diols, which should not interact
with the subcomponents employed in our previous cop-
per(I)/diimine system,[10] and would thus not be expected to
interfere with the formation of copper complexes.Both
copper and boron systems might act together to co-direct
the formation of a more complex structure by the simultane-
ous application of two distinct sets of self-assembly rules.
Experimental Section
General: All reactions were carried out using reagents of the highest
commercially available purity. p-Toluidine (3) was sublimed prior to use.
NMR spectra were assigned with the help of COSY, NOESY, and HSQC
measurements.[35] All 11B chemical shifts were referenced to BF3·Et2O at
d=0 ppm as an external standard in a sealed capillary.Methods A and B,
described below, were used in the preparation of many of the new com-
pounds, as noted.All experiments were carried out at room temperature
(RT)=(296Æ2) K unless otherwise indicated.
Method A: Into a NMR tube with a Teflon screw-cap were added the in-
dicated quantities of diol, amine, and 2-formylphenylboronic acid, to
which was added deuterated methanol (0.4 mL). All starting materials
dissolved within 5 min.After four hours, NMR spectra showed the com-
plete condensation of amine with aldehyde to form imine.The solvent
was removed under dynamic vacuum and the residue was dissolved in
CDCl3.NMR spectroscopy indicated the clean formation of a single
product.
Scheme 7.Transformation of 3(OMe)2 into 3B and subsequently into 3A.
A
Method B: Into a NMR tube with a Teflon screw-cap were added the in-
dicated quantities of polyol, amine, and 2-formylphenylboronic acid, to
which was added deuterated methanol (0.4 mL). After one night at 508C,
NMR spectra showed the complete condensation of amine with aldehyde
to form imine and all polyol had dissolved.The solvent was removed
under dynamic vacuum and the residue was dissolved in CDCl3.NMR
spectroscopy indicated the clean formation of a single product.
The addition of ethylene glycol B to a chloroform solution
of iminoboronate ester 3(OMe)2 led to its complete conver-
AHCTREUNG
sion into 3B (Scheme 7, left).We attribute the driving force
of this reaction to the gain in entropy associated with the
chelate effect.[40] The addition of an equimolar amount of
1,3-propanediol to 3B resulted in the establishment of an
equilibrium between 3B and 3C with neither predominating
(45% 3B and 55% 3C at equilibrium), in similar fashion to
what Philp et al.have observed in boroxoaromatic sys-
tems.[21] The addition of catechol A to a chloroform solution
of 3B or 3C, however, resulted in the quantitative displace-
ment of the aliphatic diol subcomponent to produce 3A.We
reasoned that the driving force for this displacement was
identical to the reason that catechol esters are more stable
3(OMe)2: Into a NMR tube with a Teflon screw-cap was added p-tolui-
A
dine (0.031 mmol, 1 equiv), 2-formylphenylboronic acid (0.031 mmol,
1 equiv), and MeOH (0.35 mL). After one hour at room temperature, the
solvent was removed and CDCl3 (0.35 mL) was added. NMR spectrosco-
1
py indicated the clean formation of a single product. H NMR (400 MHz,
298 K, CDCl3): d=8.62 (s, 1H, imine), 7.54 (m, 5H, 3-iminophenylboron-
ic ester + 5-iminophenylboronic ester + 6-iminophenylboronic ester +
aniline next to imine), 7.40 (dt, J=7.5 Hz, J’=1 Hz, 1H, 4-iminophenyl-
boronic ester), 7.26 (d, overlap with CHCl3, 2H, aniline next to methyl),
3.28 (s, 6H, -OCH3), 2.40 ppm (s, 3H, -CH3); 11B NMR (641.85 MHz,
298 K) CDCl3: d=21.6; MeOD: d=14.8; 13C NMR (100.62 MHz, 298 K,
4590
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co.KGaA, Weinheim
Chem. Eur. J. 2008, 14, 4585 – 4593

Dynamic Covalent Chemistry
FULL PAPER
CDCl3): d=159.9, 138.2, 132.4, 130.8, 128.2, 128.1, 121.3, 121.2, 51.1, 21.3;
(3.18 mg, 0.021 mmol, 1 equiv). 1H NMR (400 MHz, 298 K, CDCl3): d=
8.53 (s, 1H, imine), 7.68 (d, J=7 Hz, 1H, 6-iminophenylboronic ester),
7.64 (d, J=7.5 Hz, 1H, 3-iminophenylboronic ester), 7.60 (dt, J=7.5 Hz,
J’=1 Hz, 1H, 5-iminophenylboronic ester), 7.42 (dt, J=7.5 Hz, J’=1 Hz,
1H, 4-iminophenylboronic ester), 7.25 (d, J=8 Hz, 2H, aniline next to
imine), 7.09 (d, J=8 Hz, 2H, aniline next to -Me), 6.85 (m, 2H, catecho-
late), 6.75 (m, 2H, catecholate), 2.30 ppm (s, 3H, -CH3); 11B NMR
(641.85 MHz, 298 K) CDCl3: d=15.1 ppm; MeOD: d=14.7 ppm;
13C NMR (100.62 MHz, 298 K, CDCl3): d=166.2, 152.2, 139.6, 138.6,
137.3, 134.9, 131.3, 130.3, 129.1, 127.5, 121.9, 119.5, 110.3, 21.2 ppm. EI-
MS: 313 [3A]+.
EI-MS: 267 [3
(OMe)2]+.
A
11A (Method A): Pyrocatechol A (3.16 mg, 0.029 mmol, 1 equiv), 2-me-
thoxyethylamine (11; 2.15 mg, 0.029 mmol, 1 equiv), 2-formylphenylbor-
onic acid (4.29 mg, 0.029 mmol, 1 equiv). 1H NMR (400 MHz, 298 K,
CDCl3): d=8.34 (s, 1H, imine), 7.65 (d, J=7 Hz, 1H, 6-iminophenylbor-
onic ester), 7.54 (m, 2H, 3-iminophenylboronic ester + 5-iminophenyl-
boronic ester), 7.38 (dt, J=7.5 Hz, J’=1 Hz, 1H, 4-iminophenylboronic
ester), 6.88 (m, 2H, catecholate), 6.77 (m, 2H, catecholate), 3.65 (m, 2H,
-CH=N-CH2CH2OCH3), 3.58 (m, 2H, -CH=N-CH2CH2OCH3), 3.35 ppm
(s, 3H, -CH=N-CH2CH2OCH3); 11B NMR (641.85 MHz, 298 K) CDCl3:
d=13.3 ppm; MeOD: d=10.9 ppm; 13C NMR (100.62 MHz, 298 K,
CDCl3): d=170.1, 152.4, 137.9, 134.2, 131.1, 128.8, 26.9, 119.4, 110.3, 69.3,
59.1, 49.7 ppm; EI-MS: 281 [11A]+, 250 [11AꢀCH3O]+, 236
3B (Method A): 1,2-Ethanediol (B; 21.70 mg, 0.345 mmol, 1 equiv), p-tol-
uidine (3; 37.46 mg, 0.345 mmol, 1 equiv), 2-formylphenylboronic acid
1
(52.42 mg, 0.345 mmol, 1 equiv), and MeOH (4 mL). H NMR (400 MHz,
[11AꢀCH3OCH2]+,
222
[11AꢀCH3OCH2CH2]+,
209
298 K, CDCl3): d=8.60 (s, 1H, imine), 7.71 (dd, J=8 Hz, 2H, 3-imino-
phenylboronic ester + 6-iminophenylboronic ester), 7.50 (t, J=7.5 Hz,
1H, 5-iminophenylboronic ester), 7.41 (t, J=7.5 Hz, 1H, 4-iminophenyl-
boronic ester), 7.31 (d, J=8 Hz, 2H, aniline nexte to imine), 7.23 (d, J=
8 Hz, 2H, aniline next to -Me), 4.15 (brs, 4H, -OCH2CH2O-), 2.40 ppm
(s, 3H, -CH3); 11B NMR (641.85 MHz, 298 K) CDCl3: d=22.9 ppm;
MeOD: d=14.7 ppm; 13C NMR (100.62 MHz, 298 K, CDCl3): d=163.1,
139.4, 137.7, 132.7, 132.4, 130.1, 129.4, 127.7, 121.8, 65.6, 21.4 ppm; EI-
MS: 265 [3B]+.
[11AꢀCH3OCH2CH2N]+.
11B (Method A): 1,2-Ethanediol B (1.8 mL, 0.032 mmol, 1 equiv), 2-me-
thoxyethylamine (11; 2.40 mg, 0.032 mmol, 1 equiv), 2-formylphenylbor-
onic acid (4.78 mg, 0.032 mmol, 1 equiv). 1H NMR (400 MHz, 298 K,
CDCl3): d=8.30 (s, 1H, imine), 7.57 (d, J=7 Hz, 1H, 6-iminophenylbor-
onic ester), 7.45 (m, 2H, 3-iminophenylboronic ester + 5-iminophenyl-
boronic ester), 7.28 (t, J=8 Hz, 1H, 4-iminophenylboronic ester), 4.13 (s,
4H, -OCH2CH2O-), 3.80 (t, J=5 Hz, 2H, -CH=N-CH2CH2OCH3), 3.74
(t, J=5 Hz, 2H, -CH=N-CH2CH2OCH3), 3.37 ppm (s, 3H, -CH=N-
CH2CH2OCH3); 13C NMR (100.62 MHz, 298 K, CDCl3): d=168.8, 137.9,
133.4, 130.5, 127.9, 126.2, 69.9, 65.5, 59.1, 50.4 ppm; EI-MS: 233 [11B]+,
4A (Method A): Pyrocatechol (A; 2.80 mg, 0.025 mmol, 1 equiv), 4-
(methylmercapto)aniline (4; 3.54 mg, 0.025 mmol, 1 equiv), 2-formylphe-
nylboronic acid (3.81 mg, 0.025 mmol, 1 equiv). 1H NMR (400 MHz,
298 K, CDCl3): d=8.55 (s, 1H, imine), 7.63 (m, 3H, 3-iminophenylboron-
ic ester + 5-iminophenylboronic ester + 6-iminophenylboronic ester),
7.42 (t, J=7.5 Hz, 1H, 4-iminophenylboronic ester), 7.27 (d, overlapped
signal with CHCl3, 2H, aniline next to imine), 7.11 (d, J=8.5 Hz, 2H,
aniline next to -SMe), 6.86 (m, 2H, catecholate), 6.77 (m, 2H, catecho-
late), 2.43 ppm (s, 3H, -SCH3); 13C NMR (100.62 MHz, 298 K, CDCl3):
d=165.8, 152.0, 140.9, 137.8, 137.2, 134.9, 131.3, 129.2, 127.6, 126.7, 122.4,
119.6, 110.4, 15.4; EI-MS: 345 [4A]+, 330 [4AꢀCH3]+.
5A (Method A): Pyrocatechol (A; 2.65 mg, 0.024 mmol, 1 equiv), 4-io-
doaniline (5; 5.28 mg, 0.024 mmol, 1 equiv), 2-formylphenylboronic acid
(3.61 mg, 0.024 mmol, 1 equiv). 1H NMR (400 MHz, 298 K, CDCl3): d=
8.55 (s, 1H, imine), 7.65 (m, 5H, 3-iminophenylboronic ester + 5-imino-
phenylboronic ester + 6-iminophenylboronic ester + aniline nexte to
imine), 7.43 (t, J=7 Hz, 1H, 4-iminophenylboronic ester), 7.08 (d, J=
8.5 Hz, 2H, aniline next to -I), 6.86 (m, 2H, catecholate), 6.78 ppm (m,
2H, catecholate); 13C NMR (100.62 MHz, 298 K, CDCl3): d=167.2,
151.8, 140.7, 138.8, 137.0, 135.3, 131.4, 129.3, 128.0, 123.8, 120.8, 119.8,
110.5, 94.9 ppm; EI-MS: 425 [5A]+.
203
[11BꢀCH3O]+,
188
[11BꢀCH3OCH2]+,
161
[11BꢀCH3OCH2CH2N]+.
11C (Method A): 1,3-Propanediol C (2.8 mL, 0.039 mmol, 1 equiv), 2-me-
thoxyethylamine 11 (2.93 mg, 0.039 mmol, 1 equiv), 2-formylphenylbor-
onic acid (5.85 mg, 0.039 mmol, 1 equiv). 1H NMR (400 MHz, 298 K,
CDCl3): d=8.50 (s, 1H, imine), 7.60 (m, 2H, 6-iminophenylboronic ester
+ 3-iminophenylboronic ester), 7.41 (dt, J=7 Hz, J’=1 Hz, 1H, 5-imino-
phenylboronic ester), 7.32 (dt, J=7.5 Hz, J’=1.5 Hz, 1H, 4-iminophenyl-
boronic ester), 4.14 (t, J=5.5 Hz, 4H, -OCH2CH2CH2O-), 3.87 (t, J=
6 Hz, 2H, -CH=N-CH2CH2OCH3), 3.74 (t, J=5.5 Hz, 2H, -CH=N-
CH2CH2OCH3), 3.39 (s, 3H, -CH=N-CH2CH2OCH3), 2.04 ppm (quint.,
J=5.5 Hz, 2H, -OCH2CH2CH2O-); 13C NMR (100.62 MHz, 298 K,
CDCl3): d=165.9, 139.0, 131.9, 131.2, 128.6, 127.4, 71.6, 62.0, 59.1, 57.1,
28.3 ppm ;
EI-MS:
247
188
[11C]+,
217
[11CꢀCH3O]+,
202
175
[11CꢀCH3OCH2]+,
[11CꢀCH3OCH2CH2]+,
[11CꢀCH3OCH2CH2N]+.
1A (Method A): Pyrocatechol (A; 2.84 mg, 0.026 mmol, 1 equiv), 4-
amino-N,N-dimethylaniline (1; 3.50 mg, 0.025 mmol, 1 equiv), 2-formyl-
phenylboronic acid (3.86 mg, 0.026 mmol, 1 equiv). 1H NMR (400 MHz,
298 K, CDCl3): d=8.46 (s, 1H, imine), 7.64 (d, J=7 Hz, 1H, 6-iminophe-
nylboronic ester), 7.55 (m, 2H, 3-iminophenylboronic ester + 5-imino-
phenylboronic ester), 7.38 (dt, J=7.5 Hz, J’=1 Hz, 1H, 4-iminophenyl-
boronic ester), 7.23 (d, J=9 Hz, 2H, aniline next to imine), 6.88 (m, 2H,
catecholate), 6.78 (m, 4H, catecholate), 6.52 (d, J=9 Hz, 2H, aniline
6A (Method A): Pyrocatechol (A; 2.65 mg, 0.024 mmol, 1 equiv), 4-
chloroaniline (6; 3.06 mg, 0.024 mmol, 1 equiv), 2-formylphenylboronic
R
acid (3.61 mg, 0.024 mmol, 1 equiv). 1H NMR (400 MHz, 298 K, CDCl3):
d=8.58 (s, 1H, imine), 7.70 (m, 3H, 3-iminophenylboronic ester + 5-imi-
nophenylboronic ester + 6-iminophenylboronic ester), 7.48 (t, J=7.5 Hz,
1H, 4-iminophenylboronic ester), 7.32, (m, 4H, aniline), 6.90 (m, 2H,
catecholate), 6.81 ppm (m, 2H, catecholate);. 13C NMR (100.62 MHz,
298 K, CDCl3): d=167.1, 151.9, 139.6, 137.1, 135.3, 131.5, 129.9, 129.3,
127.9, 123.5, 119.8, 110.5 ppm. EI-MS: 333 [6A]+.
next to NMe2), 2.93 ppm (s, 6H, -N
(CH3)2); 11B NMR (641.85 MHz,
H
298 K) CDCl3: d=15.0 ppm; MeOD: d=13.6 ppm.; 13C NMR
(100.62 MHz, 298 K, CDCl3): d =161.6, 152.3, 150.8, 137.6, 133.9, 131.0,
129.7, 128.9, 126.6, 122.9, 119.4, 112.3, 110.3, 40.3 ppm; ES-MS: 372
[1A+MeO]ꢀ.
112D (Method B): Pentaerythritol (D; 3.20 mg, 0.023 mmol, 1 equiv), 2-
methoxyethylamine (11; 3.54 mg, 0.047 mmol, 2 equiv), 2-formylphenyl-
boronic acid (7.06 mg, 0.047 mmol, 2 equiv). 1H NMR (400 MHz, 298 K,
CDCl3): d=8.37 (s, 1H, imine), 7.69 (d, J=7 Hz, 1H, 6-iminophenylbor-
onic ester), 7.50 (d, J=7.5 Hz, 1H, 3-iminophenylboronic ester), 7.45 (t,
J=7.5 Hz, 1H, 5-iminophenylboronic ester), 7.29 (t, J=7.5 Hz, 1H, 4-
iminophenylboronic ester), 4.09 (s, 4H, -OCH2CCH2O-), 3.93 (t, J=5 Hz,
2H, -CH=N-CH2CH2OCH3), 3.77 (t, J=5 Hz, 2H, -CH=N-
CH2CH2OCH3), 3.39 ppm (s, 3H, -CH=N-CH2CH2OCH3); 13C NMR
(100.62 MHz, 298 K, CDCl3): d =168.3, 137.8, 132.8, 130.6, 127.9, 127.0,
70.5, 66.1 (two overlapping peaks), 59.1, 53.1 ppm; EI-MS: 478 [112D]+,
2A (Method A): Pyrocatechol (A; 2.65 mg, 0.024 mmol, 1 equiv), 4-me-
thoxyaniline (2; 3.01 mg, 0.025 mmol, 1 equiv), 2-formylphenylboronic
acid (3.61 mg, 0.024 mmol, 1 equiv). 1H NMR (400 MHz, 298 K, CDCl3):
d=8.50 (s, 1H, imine), 7.67 (d, J=7 Hz, 1H, 6-iminophenylboronic
ester), 7.60 (m, 2H, 3-iminophenylboronic ester + 5-iminophenylboronic
ester), 7.42 (dt, J=7.5 Hz, J’=1 Hz, 1H, 4-iminophenylboronic ester),
7.30 (d, J=9 Hz, 2H, aniline next to imine), 6.84 (m, 2H, catecholate),
6.77 (m, 4H, aniline next to -OMe + catecholate), 3.76 ppm (s, 3H,
-OCH3); 13C NMR (100.62 MHz, 298 K, CDCl3): d =165.1, 160.3, 152.1,
137.3, 134.7, 134.0, 131.2, 129.1, 127.3, 123.4, 119.5, 114.9, 110.4,
55.6 ppm; EI-MS: 329 [2A]+, 314 [2AꢀCH3]+.
447
[112DꢀOCH3]+,
443
[112DꢀCH3OCH2]+,
419
[112DꢀCH3OCH2CH2]+.
3A (Method A): Pyrocatechol (A; 2.33 mg, 0.021 mmol, 1 equiv), p-tolui-
dine (3; 2.28 mg, 0.021 mmol, 1 equiv), 2-formylphenylboronic acid
15A2
(Method B): Pyrocatechol (A; 2.30 mg, 0.021 mmol, 2 equiv), bis
ACHTREUNG
amino)diphenyl ether (15; 4.18 mg, 0.010 mmol, 1 equiv), 2-formylphenyl-
Chem. Eur. J. 2008, 14, 4585 – 4593
ꢀ 2008 Wiley-VCH Verlag GmbH & Co.KGaA, Weinheim
www.chemeurj.org
4591

J.R.Nitschke et al.
boronic acid (3.13 mg, 0.021 mmol, 2 equiv). 1H NMR (400 MHz, 298 K,
CDCl3): d=8.52 (s, 2H, imine), 7.69 (d, J=7 Hz, 2H, 6-iminophenylbor-
onic ester), 7.61 (m, 4H, 3-iminophenylboronic ester + 5-iminophenyl-
boronic ester), 7.43 (dt, J=7.5 Hz, J’=1 Hz, 2H, 4-iminophenylboronic
ester), 7.30 (d, J=9 Hz, 4H, aniline next to the oxygen), 6.85 (m, 8H,
aniline next to imine + catecholate), 6.74 ppm (m, 4H, catecholate);
13C NMR (100.62 MHz, 298 K, CDCl3): d =166.2, 157.2, 152.0, 137.2,
136.7, 135.1, 131.4, 129.2, 127.7, 123.8, 119.8, 119.7, 110.4 ppm; EI-MS:
612 [15A2]+.
thoxyethylamine (11; 2.27 mg, 0.030 mmol, 1 equiv) and CDCl3 (0.35 mL)
were then added.NMR spectra indicated the complete conversion of 1A
into 11A and 1 (or 3) following three hours at room temperature.No fur-
ther evolution was observed following heating of the tube to 323 K
during three days.
Preparation of 3A by diol substitution: Following Method A, compound
3B (16.89 mg, 0.064 mmol) was prepared in an NMR tube. Solvents were
subsequently removed under dynamic vacuum; catechol (A; 7.01 mg,
0.064 mmol, 1 equiv) and CDCl3 (0.35 mL) were then added. NMR spec-
tra indicated the complete conversion of 3B into 3A and B after one
hour at room temperature.No further evolution was observed following
heating of the tube to 323 K during three days.
113E: Into a NMR tube with a Teflon screw-cap were added triscatechy-
lene E (2.9 mg, 0.008 mmol), 2-methoxyethylamine (1.8 mg, 0.024 mmol),
2-formylphenylboronic acid (5.2 mg, 0.024 mmol), methanol (0.4 mL),
and [D6]DMSO (0.1 mL). After one night at room temperature, solvents
were removed under dynamic vacuum and the residue was dissolved in
CDCl3.NMR spectroscopy indicated the clean formation of a single
1
product. H NMR (500 MHz, 298 K, CDCl3): d=8.32 (s, 3H, imine), 7.57
(d, J=7 Hz, 3H, 6-iminophenylboronic ester), 7.49 (m, 6H, 3-iminophe-
nylboronic ester + 5-iminophenylboronic ester), 7.32 (t, J=7 Hz, J’=
7.5 Hz, 3H, 4-iminophenylboronic ester), 6.88 (brs, 6H, catecholate),
4.85 (d, J=13.5 Hz, 3H, -catecholate-CH2-catecholate-), 3.50 (m, 15H,
Acknowledgements
This work was made possible by the Walters–Kundert Charitable Trust,
the Swiss National Science Foundation, and the Swiss Secretariat for
Education and Research.We thank E.Sandmeyer and P.Perrottet for
mass spectrometric analyses, and A.Pinto for help with 11B NMR experi-
ments.
-catecholate-CH2-catecholate-
+ -CH=N-CH2CH2OCH3 + -CH=N-
CH2CH2OCH3), 3.31 ppm (brs, 9H, -CH=N-CH2CH2OCH3); 13C NMR
(125.77 MHz, 298 K, CDCl3): d =170.1, 150.9, 137.8, 134.0, 131.0, 130.7,
128.6, 126.7, 111.5, 69.5, 59.0, 49.3 (br), 37.2 ppm; APCI-MS (CHCl3)=
880.4 [113E]+.
[1] R.W.Saalfrank, E.Uller, B.Demleitner, I.Bernt,
Struct. Bonding
Macrocycle 162D2: Into a NMR tube with a Teflon screw-cap were added
pentaerythrytol (5.4 mg, 0.040 mmol), 1,4-diaminobenzene (4.3 mg,
0.040 mmol), 2-formylphenylboronic acid (11.9 mg, 0.080 mmol), and
[D7]DMF (0.35 mL). All starting materials dissolved within 1 h at 508C.
After two days at this temperature, yellow crystals suitable for X-ray
analysis had formed within the tube.NMR spectra of the supernatant so-
lution or of the crystals suspended in THF and DMF showed mixtures of
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3
Crystallographic data for 162D2 (C50H44B4N4O8) ; Mr =872.2, monoclinic,
¯
P1, a=9.9854(11), b=11.3648(11), c=11.7149(11) Š; a=68.199(11), b=
78.892(12), g=65.704(11)8; V=1123.8(2) Š3; Z=1, m=0.086 mmꢀ1
1calcd =1.289 gcmꢀ3
MoKa radiation (l=0.71073 Š); 14696 reflections
,
,
measured at 150 K on a STOE IPDS diffractometer, 5023 unique reflec-
tions of which 2616 with jFo j>4s(Fo).Data were corrected for Lorentz
and polarization effects and for absorption (Tmin, Tmax =0.9837, 0.9907).
The structure was solved by direct methods (SIR97).[42] All calculations
were performed with the XTAL system.[43] Full-matrix least-squares re-
2
finement based on F using weights of 1/
(s2 (Fo) + 0.0002
G
values R=0.042, wR=0.038 and S=1.33(2) for 298 variables and 2751
contributing reflections.CCDC-653019 ( 162D2) contains the supplemen-
tary crystallographic data for this paper.These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif
Mukhopadhyay, S.Chakrabarti, PY. .Zavalij, L.Isaacs,
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Cage 173E2: Into a NMR tube with a Teflon screw-cap were added cyclo-
tricatechylene E (7.77 mg, 0.021 mmol), freshly distilled m-xylylenedi-
k) F.Hof, S.L.Craig, C.Nuckolls, J.Rebek, Jr.
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114, 1556–1578; Angew. Chem. Int. Ed. 2002, 41, 1488–1508;
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A
0.060 mmol), and [D7]DMF (0.7 mL) under argon. After one night at
room temperature, proton NMR spectrum showed the clean formation of
173E2. 1H NMR (500 MHz, 298 K, [D7]DMF): d=8.56 (s, 6H, imine),
7.63 (d, J=7 Hz, 6H, 6-iminophenylboronic ester), 7.55 (m, 9H, 5 m-xy-
lylenediimine + 3-iminophenylboronic ester), 7.41 (m, 15H, 4-iminophe-
Adv. Mater. 2006,
Acc.
nylboronic ester, 5-iminophenylboronic ester
7.29 (d, J=7.5 Hz, 6H, 4 m-xylylenediimine
+
2 m-xylylenediimine),
6 m-xylylenediimine),
+
M.Kogej, C.A.Schalley, R.Froehlich,
J. Am. Chem. Soc. 2005, 127,
7.06 (s, 12H, aromatic protons from cyclotricatechylene subcomponent),
4.97 (d, J=13 Hz, 6H, aliphatic protons from cyclotricatechylene sub-
component), 4.21 (s, 12H, aliphatic protons from m-xylylenediamine sub-
component), 3.63 ppm (d, J=13.5 Hz, aliphatic protons from cyclotricate-
chylene subcomponent); 13C NMR (125.77 MHz, 298 K, [D7]DMF): d=
170.7, 151.9, 138.90, 134.9, 133.6, 133.5, 130.9, 130.7, 130.4, 128.8, 127.7,
111.1, 51.1, 37.1 ppm; MALDI-MS: 1716.63 [C108H78B6N6O12]+.
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Received: January 14, 2008
Published online: April 3, 2008
Chem. Eur. J. 2008, 14, 4585 – 4593
ꢀ 2008 Wiley-VCH Verlag GmbH & Co.KGaA, Weinheim
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4593