2
Li et al. Sci China Chem
Diels-Alder [23,39–41], Knoevenagel condensation [42] as
the dominant examples. Moreover, substrate scope and/or
product diversity for supramolecular catalysis are still very
limited, which have been generally restrained by the size of
the internal cavity and/or the apertures of the cage frame-
work.
Coumarin and its derivatives are an important group of
compounds with antibacterial, anticarcinogenic, and an-
algesic activity [43]. Herein, we report a supramolecular
synthetic route for functionalized coumarin derivatives cat-
alyzed by an organo-palladium cage with enlarged cavity.
Our results are characteristic of broad substrate scope and
mild aqueous condition. Reaction mechanism has been stu-
died in details with host-guest complexes based on the
structural elucidation of typical substrate and analogous in-
termediate revealed by X-ray crystallography. Moreover,
kinetic studies have confirmed the enzymatic reaction model
and revealed over 23-fold rate acceleration compared to the
background reaction.
Scheme 1 (a) Structure and cartoon representation of cage 1; (b) X-ray
crystal structure of 1 (for clarity, only the cationic cage skeleton is shown.
Color scheme: C, gray; H, gray; N, blue; Pd, yellow) (color online).
is similar to the well-known Pd L cage reported by the
6
4
Fujita group [45]. Due to the introduction of two p-xylene
spacers, this new generation of cage bears an expanded in-
ternal cavity than the Pd L cage (Figure S6). Moreover, with
6
4
the formation of strongly electron-deficient pyridinium rings
on the TPT panels induced by two p-xylene spacers, cage 1 is
able to bind an increased number of organic and inorganic
guests than the Fujita-cage [44].
2
Experimental
A
suspension of 2-hydroxy-1-naphthaldehyde (2a,
1
0
.72 mg, 5 equiv.) and cage 1 (6.4 mg, 2 µmol, 1 equiv.) in
2
.1 General information
.5 mL of D O was stirred for 3 h at room temperature. The
2
Unless otherwise stated, all reagents were purchased from
commercial sources and used without further purification.
Deuterated solvents were purchased from Admas, J&K
Scientific and Sigma-Aldrich. 1D and 2D NMR spectra were
measured on a Bruker Biospin Avance III (400 MHz) spec-
homogeneous solution was obtained, indicative of the en-
capsulation of 2a by cage 1, which was further confirmed by
1
the up-field shift of 2a signals in H NMR. The host-guest
ratio was determined as 1:4 based on NMR integrals (Figure
1(A–D)). The host-guest complex (2a) @1 was also char-
4
1
1
1
1
13
trometer (Germany). H NMR chemical shifts were de-
acterized by H NMR, H- H COSY, C NMR (Figures S7–
termined with respect to residual signals of the deuterated
solvents used. The chemical shifts (δ) in the NMR spectra are
reported in ppm relative to tetramethylsilane (TMS) as an
internal standard (0.00 ppm) or proton resonance resulting
from incomplete deuteration of the solvents (CD ) SO
S9). Notably, the DOSY showed a clear single band at logD=
−
10
2
−9.628 (diffusion coefficient D=2.35×10 m /s), which
was consistent with that of the empty cage (Figure S10). The
NMR titration corroborated further a cooperative 1:4 host-
guest stoichiometry of cage 1 toward 2a (Figure S11).
3
2
(
2.50 ppm), CDCl (7.26 ppm) and D O (4.79 ppm). The gas
Structure of (2a) @1 was also confirmed by X-ray crys-
3
2
4
chromatograph-mass spectrometer (GC-MS) was measured
with GCMS-QP2010 SE (Shimadzu, Japan).
tallographic analysis (Figure 2), which shows that four guest
molecules are located inside the cage. One external binding
guest sticking to the surface of cage 1 was also observed,
possibly due to the cage-enhanced solubility of the 2a in
water. All of guests show π-π stacking interactions with the
TPT panels. Due to the hydrophilic nature, the aldehyde and
hydroxyl groups of the internal guests point to the portals of
the cage 1.
2
.2 Synthesis and characterization of cage 1 and cou-
marin 4aa
The Pd L -type organo-palladium cage 1 (Scheme 1) was
4
2
synthesized quantitatively following a reported procedure
44] by simply replacing the cis-blocking unit from bpy to
Having confirmed the encapsulation of 2a inside cage 1,
ethyl cyanoacetate (3a, 3.40 mg, 15 equiv.) was subsequently
[
added into the aqueous solution of (2a) @1 (Figure 1(D)).
4
After heating at 50 °C for 35 h, the reaction product was
1
13
The structure of cage 1 was characterized by NMR ( H, C,
extracted with CHCl , then the compound 4aa in yield of
3
1
1
H- H COSY, diffusion-ordered NMR spectroscopy
8
0.5% was obtained (Figure 1(E)), which was confirmed by
GC-MS (Figure S16(b)). In a control experiment where no
cage 1 was used, guest 2a reacted with 3a gave rise to 4aa in
a much reduced yield (37.5%). The reactivity in the presence
Scheme 1(b), cage 1 is a pseudo-octahedral structure which