Evaluation of the Catalytic Capability of cis- and trans-Diquinoxaline Spanned Cavitands

Article abstract of DOI:10.1002/ejoc.201901058

Three new cis-diquinoxaline spanned cavitands were successfully synthesized. These cis-diphosphinated derivatives were applied in homogeneous gold-catalyzed dimerization and hydration of alkynes as well as rhodium-catalyzed styrene hydroformylation. The results were ranked with those obtained with their trans-diphosphinated isomeric analogues. The structure-activity relationship employing these two cavitands reveals that the cis- or trans-positioning of the catalyst centers directly influences cooperation between the two metallic atoms to control catalytic activity, reaction profile, and product selectivity. This comparative study provides us an intellectual basis for future catalytic cavitand chemistry and homogeneous catalysis.

Full text of DOI:10.1002/ejoc.201901058

DOI: 10.1002/ejoc.201901058
Full Paper
Cavitands in Catalysis
Evaluation of the Catalytic Capability of cis- and trans-
Diquinoxaline Spanned Cavitands
[
a]
[a]
[a]
[b,c]
Jules Bouffard,[b]
Mami Inoue, Shinsuke Kamiguchi, Katto Ugawa, Shaima Hkiri,
[b]
[a]
David Sémeril,* and Tetsuo Iwasawa*
Abstract: Three new cis-diquinoxaline spanned cavitands were ture-activity relationship employing these two cavitands reveals
successfully synthesized. These cis-diphosphinated derivatives that the cis- or trans-positioning of the catalyst centers directly
were applied in homogeneous gold-catalyzed dimerization and influences cooperation between the two metallic atoms to con-
hydration of alkynes as well as rhodium-catalyzed styrene trol catalytic activity, reaction profile, and product selectivity.
hydroformylation. The results were ranked with those obtained This comparative study provides us an intellectual basis for fu-
with their trans-diphosphinated isomeric analogues. The struc- ture catalytic cavitand chemistry and homogeneous catalysis.
Introduction
Resorcin[4]arene-cavitand, able to carry out a catalytic reaction,
is an important supramolecule that mimics enzymatic catalysis
and achieves marvelous chemical transformations from the
gold cavitand was efficient in the dimerization of two different
[
10]
terminal alkynes.
Another type of gold cavitand, in which a
[
1–3]
viewpoint of green chemistry.
The cavitands have strong
resemblances in two points to natural enzymes: one, cavitands
are partly open, guest substrates readily fill the space, enter and
leave; the second, cavitands are endowed with gently curved
concave large enough to accommodate catalytic centers. De-
spite the relevant role played by catalytic cavitands, such a class
of cavitands is underrepresented owing to synthetic difficul-
ties.[
4,5]
To make supramolecular cavitands those weigh over
MW ca. 1000 preparatively in pure form is a basically embarrass-
ing synthesis. When we attempt to introduce reactive centers
inside the hydrophobic pockets, isomeric production of in- and
outwardly oriented cavitands towards the pockets often occurs.
Hence, we chemists are always struggling to understand even
[
6]
basic aspect of cavitand catalysis. It might be quite a chal-
lenge for us to imitate enzymatic virtue that Mother Nature has
meticulously created for more than long, long four billion years,
because synthetic chemistry has been in just one or two hun-
dred year-period history since Friedrich Wöhler synthesized
[
7,8]
urea from ammonium cyanate.
Recently, we have developed for catalytic applications trans-
[
9]
di-quinoxaline-spanned resorcin[4]arenes. An introverted bis-
[
[
[
a] Department of Materials Chemistry, Ryukoku University,
Seta, Otsu, Shiga, 520-2194, Japan
E-mail: iwasawa@rins.ryukoku.ac.jp
http://www.chem.ryukoku.ac.jp/iwasawa/index.html
b] Synthèse Organométallique et Catalyse, UMR-CNRS 7177,
Université de Strasbourg,
4
rue Blaise Pascal, 67070 Strasbourg Cedex, France
E-mail: dsemeril@unistra.fr
c] Faculté des Sciences de Bizerte, Université de Carthage,
7
021 Jarzouna, Bizerte, Tunisia
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201901058.
Figure 1. Diquinoxaline-spanned resorcin[4]arenes those are in cis-1, cis-2 and
cis-3 and in trans-4, trans-5 and trans-6.
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Lewis acid gold cation was associated to a Lewis basic P=O ure 2 (a)); in the spectrum of iso-1, two doublets at 3.87 ppm
3
3
moiety, displayed high regio-selectivities in addition of H O to ( J = 8.6 Hz) and at 3.20 ppm ( J = 12.6 Hz), which can be
2
PH
PH
unsymmetrical alkynes; for example, 3-octanone was yielded attributed to the two kinds of “in-out” POCH protons (Figure 2
3
[
11]
in 91 % starting from 3-octyne.
Although the advantage of (b)). The latter upfield-shifted doublet (δ = 3.20 ppm) results
cavitand catalysis in selective transformations are obvious, yet from anisotropic effects of the aromatic π clouds; thus, the
a study of structure-activity relationship is not obvious enough. OCH group resides inside. Consequently, in cavitand 1, the two
3
Particularly, from the viewpoint of basic research, comprehen- POCH moieties pointed outside: this was similar observation
3
3
sion of mechanistic aspects awaits upgrading. Herein we report to previously reported cavitands 4 (δ = 3.97 ppm, J = 8.7 Hz,
a structure-activity relationship of phosphinated cavitands in Figure 2 (c)) and iso-4 in Figure 3 (δ = 3.98 ppm, J = 8.3 Hz
transition metal-catalysis. We prepared new cis-type P(III) (1 and and δ = 3.10 ppm, J = 12.4 Hz, Figure 2 (d)). Oxidation of
PH
3
PH
3
PH
2
) and mixed P(III)/P(V) (3) extended cavitands, which are struc- only one phosphorus atom of 1 was carried out in the use of
turally similar to previously reported trans-type 4, 5, and 6 (Fig- 1.0 equivalent mCPBA (meta-chloroperbenzoic acid), and 3 was
[
14]
ure 1): those are used as ligands in gold- and rhodium-catalysis. isolated in 30 % yield (Scheme 1(c)). The cis-tetra-ol platform
The question we pursue here is “How does the difference be- also reacted with P[N(CH ) ] , and a mostly single spot on TLC
3
2 3
tween these trans- and cis-arrangements affect the catalytic activ- was observed, and desired 2 was obtained in 40 % yield in pure
1
ity and selectivity?”
form (Scheme 1(a)); in the H NMR spectrum of 2, there is one
Results and Discussion
We started to synthesize cis-1 from a reaction between resor-
cin[4]arene and 2,3-dichloroquinoxaline (Scheme 1(a)). Prepara-
tion of cis-positioned di-quinoxaline-spanned resorcin[4]arene
[
12]
was laborious,
2.2.2]octane) and pyridine improved the chemical yield to
2 %. The obtained cis-positioned tetra-ol cavitand reacted with
P(OCH ) to give two of the three possible isomers (“out-out”,
and the use of DABCO (1,4-diazabicyclo-
[
2
3
3
“
in-out”, and “in-in”). The two compounds were carefully sepa-
rated by silica-gel column chromatography and were isolated
in 44 % and 22 % yield for “out-out” 1 and “in-out” iso-1, re-
[
13]
spectively (Scheme 1(b)). Orientation of the lone pair of the
1
phosphorus atoms was deduced from their H NMR spectra. In
Figure 2. Portions of 1H NMR spectra (400 MHz, CDCl
, (d) iso-4. The peaks labeled with circles and triangles correspond to inward-
and outward-oriented POCH , respectively.
) of (a) 1, (b) iso-1, (c)
3
1
the case of 1, its H NMR spectrum reveals one doublet located
at 3.87 ppm ( J = 8.6 Hz) for the two “out-out” POCH (Fig-
4
3
PH
3
3
Scheme 1. (a) Synthesis of cis-1 and cis-2; (b) iso-1 bearing both inward- and outward POCH
3
groups; (c) synthesis of cis-3 (mCPBA = meta-chloroperbenzoic
acid).
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doublet peak located at 2.76 ppm with 3JPH = 10.5 Hz that can formances in catalysis will be ranking with the trans-4·(AuCl)
2
[
9b,17]
be attributed to PN(CH ) . As previously reported, we observed and trans-6·AuCl complexes.
3
2
trans-5 as a single isomer, due to steric reason, with similar
3
2
.81 ppm with J = 10.5 Hz, and ensured that two PN(CH3)2
PH
groups clearly point outside on the basis of crystallographic
analysis; thus, two PN(CH ) bonds of cis-2 were inferred to di-
3
2
[
15]
rect outwardly.
Scheme 2. Complexation between cavitands and AuCl·S(CH
of (a) 1·(AuCl) , and (b) 3·AuCl.
3
)
2
for synthesis
2
Figure 3. Structures of (a) iso-4 that has both in- and outside P-OMe, and
For the gold-catalyzed dimerization of terminal alkynes, the
(
b) mono-phosphoramidite 8 that was flanked by three quinoxalines.
runs were carried out using 1 mol-% of cis-1·(AuCl) or trans-
2
4
·(AuCl) complex and 2 mol-% of AgOTf in toluene at room
2
The conformational flexibility of tetra-quinoxaline-spanned
temperature (Scheme 3). In use of cis-1·(AuCl)2 whether for
cross-dimerization of ethynylbenzene and 1-octyne (in part (a))
or for homo-dimerization of 1-octyne (in part (b)), only
resorcin[4]arenes is well known, and can fluctuate between
[
16]
vase (close) and kite (open) conformations. The conformation
1
of the related cavitands is deduced from its H NMR spectra,
2
-octanone (7c) that results from hydration of 1-octyne was
because the chemical shift of methine protons directly beneath
quinoxaline moieties explains vase or kite form. A chemical shift
at around 5.5 ppm indicates a vase conformer, whereas a chem-
ical shift at ca. 3.7 ppm expresses a kite version. For our four
observed in 29 % and 35 % yield, respectively. These results
contrast with those observed when the tests were repeated
using the trans-4·(AuCl) complex. The trans-4·(AuCl) formed
only dimer products, with a ratio cross-7a/homo-7b = 75:25 (in
part (a)) and with >99 % yield of 7b (in part (b)). These results
2
2
1
new compounds (1, iso-1, 2 and 3), H NMR investigations car-
ried out in CDCl and [D ]toluene, clearly indicate a vase confor-
3
8
mation of the cavitands: the methine protons appear at 5.73
1), 5.76 and 5.71 (iso-1), 5.70 (2), 5.79–5.71 (3) ppm in CDCl3,
and at 6.14 (1), 6.15 and 6.08 (iso-1), 6.15 (2) and 6.20 and 6.11
3) ppm in [D ]toluene. Then, we had an interest in the differ-
(
(
8
ence in π-clouded environment between cis- and trans-walled
cavitands. For that, we compared the chemical shifts of the CH3
proton of the POCH moieties in cavitands iso-1 and iso-4. As
3
shown in Figure 2 (b) and (d), these Δδ (differences in the
chemical shifts between inward- and outward-oriented POCH3)
are 0.66, and 0.88 for iso-1 and iso-4, respectively. This result
is important evidence suggesting that the trans-walls create a
definite compartment that is more heavily influenced by the
π-clouds than the compartment of the cis-walled cavitand.
Phosphites
1 and 3 readily formed complexes with
AuCl·S(CH ) . When Au/P ratios of 1.2:1 in toluene were used,
3
2
cis-1·(AuCl) and cis-3·AuCl complexes were isolated in quanti-
2
tative and 63 % yields, respectively (Scheme 2). These gold
complexes were tested in cross- and homo-dimerization of alk-
ynes as well as in hydration of di-substituted alkynes. Their per-
2 2
Scheme 3. Catalytic evaluation of cis-1·(AuCl) and trans-4·(AuCl) in (a) cross-
dimerization, and (b) homo-dimerization.
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clearly show the importance of the positioning of the two gold
centers on the resorcin[4]arene skeleton. Different bis-gold
complexes between cis- and trans-walled cavitands led to differ-
ent type of active species and catalytic outcome. Cis-positioning
phosphorus atoms led to a more open cavitands, which leads
to a highly reactive species toward traces of water present in
commercially available dry toluene.
Differences in activity and regioselectivity could also be
highlighted in the gold-catalyzed hydration of internal alkynes
using mixed P(III)/P(V) cavitands, in which the two phosphorus
atoms are cis- or trans-positioning, cis-3·AuCl or trans-6·AuCl,
respectively (Scheme 4). For hydration of 1-phenyl-1-butyne,
the cis-3·AuCl led to low activity and selectivity (in part (a)):
Scheme 5. Rhodium-catalyzed hydroformylation reaction of styrene.
respectively, were observed in a P/Rh ratio of 4 (entries 2, 5 and
8
3
). Interestingly, the product distribution of around 7h/7i =
5:65 was not affected by the excess of cis-2, contrary to the
other two (entries 1–3). Actually, in the case of trans-5, the
P/Rh ratio drastically affects the distribution (entries 4–6): the
proportion of branched aldehyde increases with the number of
extra-added trans-5. The distributions were mostly the same
when trans-5 or 8 was used in P/Rh = 10, the branched was
formed in 78 % or 76 %, respectively (entries 6 and 9).
1-phenyl-1-butanone (7d) and 1-phenyl-2-butanone (7e) were
obtained in 5 % and 10 % yield, respectively. While repeating
the run with trans-6·AuCl, the compounds 7d and 7e were iso-
lated in 2 % and 88 % yield, respectively. A better regioselecti-
vity was also observed when trans-6·AuCl was employed in the
hydration of 3-octyne, the ratio 4-octanone (7f)/3-octanone
Table 1. Catalytic evaluation of cis-2, trans-5, and 8 in styrene hydroformyl-
(
7g) = 9:91 (in part (b)). The ratio 7f/7g decreased to 46:54
ation: influence of P/Rh ratios.[
a]
when cis-3·AuCl was used. These results indicate that less aniso-
tropic effect in the cis-cavitand would cause less stabilization
effect by π-orbital mixing with reaction process, and that the
geometrically open space in cis-form allows various transition-
Entry
Ligand
cis-2
trans-5
8
P/Rh[b]
Conv./%
Product distribution
Linear
Branched
1
2
3
2
4
10
91
96
100
35
34
37
65
66
63
[
18]
state geometries to lower selectivity.
4
5
6
2
4
10
98
99
99
52
39
22
48
61
78
7
8
9
2
4
10
64
64
54
31
31
24
69
69
76
[
a] Reactions were carried out in conditions of Scheme 5 at 80 °C for 24 h. The
conversions and products distributions were determined by GC (n-decane as
1
internal standard) and by H NMR. [b] Ratios of phosphorus atom per rho-
dium atom.
In a second series of runs, we investigated the influence of
the temperature from 60 °C to 140 °C for 5 h in a P/Rh ratio of
2
(Table 2). As general trends, the conversion increases with the
temperature up, and the regioselectivity of the catalysis
changes from mainly branched aldehyde at low temperature to
mainly linear aldehyde at high temperature. For example, in a
use of trans-5, conversion of 52 % with 16:84 ratio were ob-
served at 60 °C against a full conversion with 64:36 ratio at
Scheme 4. Catalytic evaluation of cis-3·AuCl and trans-6·AuCl in hydration
reactions of (a) ethynylbenzene, and (b) 3-octyne.
1
20 °C (entries 8 and 13). For the tests carried out at 140 °C,
Next, the three cavitands bearing phosphoramidite moieties lower conversions arose from catalyst decomposition (entries 7
(
cis-2, trans-5 and 8[19]) were assessed in styrene hydroformyl- and 21). We observed di-phosphane (cis-2 and trans-5) led to
ation (Figure 3, Scheme 5). The catalytic systems were gener- higher activities than mono-phosphane 8, especially at low
ated in situ by mixing ligand with Rh(acac)(CO) precursor, and temperature. In fact, at 60 °C, conversions of 59 %, 52 % and
2
the reactions were carried out in toluene under 20 bar of 11 % were measured when ligands cis-2, trans-5 and 8 were
CO/H (1:1) with a styrene/Rh ratio of 5000.
employed, respectively (entries 1, 8 and 15). Similarly, a higher
2
In a first series of tests that are conducted at 80 °C in 24 h, distribution toward linear aldehyde was observed when cis-2
varied amount of the cavitand was studied (Table 1). The num- and trans-5 were used rather than 8, proportion of 35 %, 51 %
bers of P/Rh ratio were varied from 2 to 10. In the case of and 31 % were obtained, respectively (entries 2, 9 and 16). Once
mono-dentate 8, conversions of 64 % and 54 % were measured the rhodium complexes formed in situ, the catalysts kept the
when P/Rh ratios of 2 and 10 were employed, respectively (en- stable state, because similar catalytic outcomes were observed
tries 7 and 9). Di-phosphoramidites cis-2 and trans-5 were more during the first 5 h of reactions at 120 °C (entries 4–6, 11–13
efficient than 8, because conversions of 96 %, 99 % and 64 %, and 18–20). The main differences between cis-2 and trans-5 is
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that cis-2 produced less thermally stable active species than atom of rhodium is coordinated to the ligand and the second
those formed by trans-5, because lower activities were meas- phosphorus atom remained free: actually, product distributions
ured at 120 °C and 140 °C (entries 5–7 and 12–14). Actually, at in trans-5 and 8 were mostly the same. For cis-2, according to
the end of the reaction course in use of cis-2, small amounts molecular modeling, the distance between the two phosphorus
of black insoluble materials, presumably rhodium colloids were atoms (ca. 6.5 Å) was important to allow the formation of
observed.
rhodium-chelate complexes. The shorter distance, compared to
trans-5, should reinforce the cooperation between the two
metal centers, which led to a more efficient system as observed
at low temperature. However, the shorter distance may be re-
sponsible for the low thermal stability and rhodium agglomera-
tion. The cis-2 has wider open cavity than trans-5, so the steric
hindrance generated by the two quinoxaline-walls was reduced;
consequently, the proportion of branched aldehyde might in-
crease. Moreover, in the case of cis-2, according to molecular
modeling, the distance between the two phosphorus atoms (ca.
6.5 Å) exclude the formation of rhodium-chelate complexes.
The shorter distance, compared to trans-5, should reinforce the
cooperation between the two metal centers, which led, as ob-
served at low temperature, to a more efficient catalytic system.
However, the shorter distance between the two rhodium atoms
and the more open structure may be responsible at high tem-
perature for the lower stability for the active species. Their deg-
radation led to the formation of rhodium-rhodium bonds and
in fine to the formation of colloids.
Table 2. Catalytic evaluation of cis-2, trans-5, and 8 in styrene hydroformyl-
ation: influence of the temperature.
[
a]
Entry
Ligand
T/°C
t/h
Conv./%
Product distribution
Linear/%
Branched/%
cis-2
1
2
3
4
5
60
5
59
88
92
41
48
33
35
56
66
63
67
65
43
34
37
80
5
100
120
120
5
0.5
2
6
7
120
140
5
5
69
60
65
62
35
38
trans-5
8
9
60
5
52
75
89
48
89
16
51
58
56
63
84
49
42
44
37
80
5
1
1
1
0
1
2
100
120
120
5
0.5
2
1
1
3
4
120
140
5
5
100
100
64
64
36
36
Conclusions
In summary, three cavitands having a cis-arrangement of two
quinoxaline walls (cis-1, –2, and –3) were successfully synthe-
sized. These cavitands, in which two catalytic centers are in-
wardly oriented, provide new architecture for transition metal
catalysis. Gold-catalyzed dimerization and hydration of alkynes
and rhodium-catalyzed styrene hydroformylation were carried
out with these cis-type cavitands. Comparative studies with iso-
mers trans-4, –5, and –6 allow us to evaluate the structure-
activity relationship. The catalytic results strongly suggest two
salient features. Firstly, the less impeded cis-environment
around the metal center reduced or modified the product distri-
bution as compared to those observed with trans-spanned li-
gand. Secondly, the distance between the two phosphorus
atoms is shorter in the cis-types than trans-versions: although a
shorter distance promotes cooperation between the two metal
centers, as observed in the styrene hydroformylation, it might
favor the leach of the rhodium metal away from the ligand and
formation of rhodium aggregations. To the best of our knowl-
edge, this work represents the first examples in homogeneous
catalysis of comparative studies involving ligands built on ex-
tended cavitands having a cis- or a trans-positioning of two
active centers. Further developments of cavitand catalysts are
ongoing and will be reported in due course.
1
1
1
1
1
2
2
5
6
7
8
9
0
1
8
60
80
5
5
5
0.5
2
11
40
82
17
69
91
54
18
31
58
56
66
64
68
82
68
42
44
34
36
32
100
120
120
120
140
5
5
[
a] Reactions were carried out in conditions of Scheme 5 with P/Rh = 2 (ratio
of phosphorus atom per rhodium atom). The conversion and product distri-
butions were determined by GC (n-decane as internal standard) and by
NMR.
1
H
From these hydroformylations, the following information of
the catalyst systems could be deduced: for 8, due to the steric
hindrance, formation of RhL2 complex should be excluded.
Generation of singly ligated active species favor the formation
of Rh(η -styrenyl)(8)(CO)2 over the less stable Rh(σ-ethyl-
phenyl)(8)(CO) species; which means the catalyst favors forma-
3
2
[
20]
tion of the branched aldehyde at low temperature.
At high
temperature, thermal agitation generates strong steric interac-
tions between the coordinated substrate and cavity wall; such
metal confinement favors the formation of the linear alde-
hyde. For trans-5, due to the distance between the two phos-
phorus atoms (9.7 Å based on the crystallographic result of
[
21]
[
8]
trans-5·(AuCl)2),
formation of rhodium-chelate complexes
should be excluded. Nevertheless, the proximity of two-coordi-
nated rhodium atoms, on the same cavitand, may allow to con-
sider a cooperation between these two metal centers. In fact,
the higher activity and selectivity toward the linear aldehyde
Experimental Section
[
22]
General Methods: All reactions sensitive to air or moisture were
carried out under an argon or a nitrogen atmosphere and anhy-
regarding 8 are arguments in that sense. Furthermore, when a drous conditions unless otherwise noted. Dry solvents were pur-
large excess of trans-5 was used, we can assume that only one chased and used without further purification and dehydration. All
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reagents were purchased and used without further purification. An-
alytical thin layer chromatography was carried out on Merck silica
2.6 Hz), 136.54, 136.45, 135.9, 135.7, 135.4, 134.8, 134.4, 129.8, 129.7,
129.5, 129.4, 128.5, 128.3, 127.8, 124.1, 123.1, 122.6, 121.7, 119.1,
6
6
0F254. Column chromatography was carried out with silica gel 118.0, 117.7, 116.8, 51.9 (d, JC,P = 22.2 Hz), 50.2 (d, JC,P = 2.6 Hz),
0N (Kanto Chemical Co.). LRMS and HRMS were reported on the
36.7, 35.9, 34.5, 34.4, 32.8, 32.5, 32.3 (many peaks are overlapped),
31.8, 31.1, 30.2, 30.12, 30.09 (many peaks are overlapped), 30.05,
30.01, 29.78, 29.75, 28.4, 28.3, 23.1, 23.0 (many peaks are over-
basis of TOF (time of flight)-MS (MADI-TOF or LCMS-IT-TOF), and
1
13
DART (Direct Analysis in Real Time)-MS. H and C NMR spectra
were recorded with a 5 mm QNP probe at 400 MHz and 100 MHz,
respectively. Chemical shifts are reported in d (ppm) with reference
lapped), 14.5 (many peaks are overlapped) ppm; 31P{ H} NMR
1
–
(162 MHz, CDCl ) 125.6, 110.6 ppm; MS (ESI) m/z: 1512 [M + Cl] ; IR
3
1
–1
to residual solvent signals [ H NMR: CHCl (7.26), C H (2.08), C H
(neat): ν = 2922, 2851, 1578, 1482, 1412, 1352, 1146, 1029, 760 cm ;
3
7
8
6
6
˜
13
–
(7.16), CH Cl (5.32); C NMR: CDCl (77.0)]. Signal patterns are indi- HRMS (ESI) calcd. for C H N O P Cl: 1511.8021 [M + Cl] , found
2
2
3
90 118 4 10 2
cated as s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet;
1511.8021.
1
3
br, broad. Assignment of C NMR was carefully performed with
13
Synthesis of 2: (see Scheme 1 (a)) To the tetra-hydroxy cis-cavitand
platform (272 mg, 0.2 mmol) in a 20 mL Schlenk tube under Ar
were added toluene (2 mL) and Et N (0.13 mL, 0.96 mmol). After
the mixture was stirred for 10 min, P[N(CH ) ] was added and the
reaction mixture was heated at 75 °C for 1 h. The mixture was
cooled to room temperature, filtered, washed with toluene, and
then the filtrate was concentrated in vacuo to give 309 mg of crude
products. Purification by short-plugged column chromatography
labeling the corresponding numbers those were listed in C NMR
spectra.
3
Synthesis of 1 and iso-1: (see Scheme 1 (a) and (b)) To the Schlenk
tube charged with a solution of the tetra-hydroxy cis-cavitand
3
2 3
(407 mg, 0.3 mmol) in dry toluene (3 mL) under N2 at 135 °C,
EtN(iPr)2 (0.52 mL, 3.0 mmol) and P(OCH3)3 (0.29 mL, 2.4 mmol)
were added. After stirred for 6 h, the reaction mixture was cooled
to room temperature and concentrated to give 457 mg of crude
products as pale yellow solid materials. Purification by silica-gel col-
umn chromatography (eluent: hexane/EtOAc, 19:1) afforded 195 mg
of 1 (“out-out”) as white solid materials in 44 % yield and 98 mg of
iso-1 (“in-out”) as white solid materials in 22 % yield.
(eluent, CHCl only) afforded 138 mg of white solid materials, which
3
were recrystallized from EtOH/EtOAc (8 mL/4.5 mL) to yield 2 in
1
40 % (120 mg) as colorless crystals. H NMR (400 MHz, CDCl ) 8.39
3
(
7
s, 1H), 7.99 (dd, J = 8.5, 8.4 Hz, 2H), 7.80 (dd, J = 8.2, 1.4 Hz, 2H),
.61–7.51 (m, 4H), 7.32 (s, 2H), 7.19 (s, 1H), 7.18 (s, 2H), 7.12 (s, 1H),
6.33 (s, 1H), 5.70 (t, J = 8.2 Hz, 2H), 4.55 (t, J = 7.6 Hz, 2H), 2.77 (d,
1
Data for 1: H NMR (400 MHz, CDCl ) 8.41 (s, 1H), 7.98 (d, J = 8.2 Hz,
3
3
JPH = 10.6 Hz, 12H, N(CH ) ), 2.28–2.17 (m, 8H), 1.41–1.27 (m, 72H),
2
3
7
1
H), 7.82 (d, J = 8.2 Hz, 2H), 7.62–7.52 (m, 4H), 7.38 (s, 2H), 7.21 (s,
3 2
0
.90–0.87 (m, 12H) ppm; 1H NMR (400 MHz, [D ]toluene) 8.83 (s,
H), 7.17 (s, 1H), 6.46 (s, 1H), 5.73 (t, J = 7.8 Hz, 2H), 4.54 (t, J =
8
3
1H), 7.88 (d, J = 8.2 Hz, 2H), 7.75 (s, 2H), 7.72 (s, 1H), 7.68 (s, 2H),
7.60 (s, 1H), 7.48 (d, J = 8.2 Hz, 2H), 7.19 (ddd, J = 8.2, 8.2, 1.0 Hz,
.8 Hz, 2H), 3.88 (d, J = 8.6 Hz, 6H, POCH ), 2.30–2.17 (m, 8H),
PH
3
1
.43–1.27 (m, 72H), 0.90–0.87 (m, 12H) ppm; H NMR (400 MHz,
2
2
1
H), 7.05–7.01 (m, 2H), 6.15 (t, J = 8.1 Hz, 2H), 4.97 (t, J = 7.4 Hz,
H), 2.52 (d, J = 10.2 Hz, 12H, N(CH ) ), 2.49–2.09 (m, 8H), 1.51–
.30 (m, 72H), 0.96–0.93 (m, 12H) ppm; C{ H} NMR (100 MHz,
[
D ]toluene) 8.82 (s, 1H), 7.85 (d, J = 8.2 Hz, 2H), 7.78 (s, 2H), 7.69
8
3
(s, 2H), 7.66 (s, 2H), 7.58 (s, 1H), 7.49 (d, J = 8.2 Hz, 2H), 7.18 (dd, J =
PH
3 2
13
1
8
2
2
.1, 7.4 Hz, 2H), 7.06–7.01 (m, 2H), 6.32 (s, 1H), 6.14 (t, J = 8.1 Hz,
3
CDCl ) 153.3, 153.1, 153.0, 152.6, 149.8 (two peaks are overlapped),
H), 4.87 (t, J = 7.8 Hz, 2H), 3.65 (d, JPH = 8.6 Hz, 6H, POCH ), 2.46–
3
3
4
13
1
149.3 (two peaks are overlapped), 140.3 (d, Jcp = 9.3 Hz), 137.7,
.35 (m, 8H), 1.50–1.29 (m, 72H), 0.97–0.92 (m, 12H) ppm; C{ H}
1
1
3
36.5, 135.7, 134.5, 129.2, 128.3, 123.9, 122.6, 121.8, 119.1, 117.8,
17.0, 35.4 (d, J = 18.8 Hz, two peaks are overlapped), 35.8, 34.4,
2.6, 32.3, 31.6, 30.1, 29.8, 28.4, 28.3, 23.1, 14.5 (many peaks are
NMR (100 MHz, CDCl ) 153.2, 153.03, 152.98, 152.9, 147.3, 147.2,
3
2
1
47.10, 147.06, 140.03, 137.6 (d, JC,P = 2.6 Hz), 136.5, 135.3, 129.6,
CP
1
29.4, 128.4, 128.2, 123.8, 122.9, 122.3, 119.2, 118.1, 117.4, 50.4 (d,
31
1
overlapped) ppm; P{ H} NMR (162 MHz, CDCl ) 140.6 ppm; MS
JC,P = 2.6 Hz), 35.9, 34.4, 32.9, 32.3 (many peaks are overlapped),
0.1 (many peaks are overlapped), 29.8 (many peaks are over-
3
–
(
1
ESI) m/z: 1539 [M + Cl] ; IR (neat): ν˜ = 2922, 2851, 1577, 1481, 1412,
3
–
1
332, 1158, 977, 758 cm ; HRMS (ESI) calcd. for C H N O P Cl:
lapped), 28.4, 28.3, 23.1 (many peaks are overlapped), 14.5 (many
92 124 6 8 2
3
1
1
1538.8678, found 1538.8668; Anal. Calcd for C H N O P :
C, 73.47; H, 8.31; N, 5.59; found C, 73.47; H, 8.37; N, 5.66.
peaks are overlapped) ppm;
1
1
P{ H} NMR (162 MHz, CDCl )
92 124 6 8 2
3
–
27.3 ppm; MS (ESI) m/z: 1512 [M + Cl] ; IR (neat): ν˜ = 2922, 2851,
–
1
606, 1578, 1482, 1412, 1332, 1158, 1029, 759 cm ; HRMS (ESI)
Synthesis of 3: (see Scheme 1(c)) To 1 (148 mg, 0.1 mmol) in tolu-
ene (4 mL) at 0 °C was slowly added a cooled-toluene solution of
–
calcd. for C H N O P Cl: 1511.8017 [M + Cl] , found 1511.8000.
90
118
4 10 2
1
Data for iso-1: H NMR (400 MHz, CDCl ) 8.36 (s, 1H), 7.99 (d, J = mCPBA (75 %, 23 mg, 0.1 mmol) over 3 min. After stirring at 0 °C
3
8
.0 Hz, 1H), 7.97 (d, J = 7.8 Hz, 1H), 7.84 (d, J = 8.1 Hz, 1H), 7.644
for 1.5 h, the reaction was quenched with saturated aqueous
(
(
5
d, J = 8.2 Hz, 1H), 7.643–7.51 (m, 4H), 7.39 (s, 1H), 7.28 (s, 1H), 7.22
NaHCO (2 mL), and stirred at ambient temperature for 30 min. The
3
s, 2H), 7.15 (s, 1H), 7.11 (s, 1H), 6.31 (s, 1H), 5.76 (t, J = 7.8 Hz, 1H),
mixture was transferred into a 50 mL separatory funnel, washed
with water (10 mL) and brine (10 mL), dried with Na SO , and con-
3
.71 (t, J = 7.8 Hz, 1H), 4.53–4.46 (m, 2H), 3.87 (d, J = 8.6 Hz, 3H,
PH
2
4
3
POCH ), 3.21 (d, J = 12.6 Hz, 3H, POCH ), 2.29–2.17 (m, 8H), 1.41–
1
centrated in vacuo to give a crude of 143 mg as a white solid
3
PH
3
1
.27 (m, 72H), 0.90–0.87 (m, 12H) ppm; H NMR (400 MHz, [D ]tolu- material. Purification by short-plugged column chromatography
8
ene) 8.82 (s, 1H), 8.03 (d, J = 8.3 Hz, 1H), 7.81 (d, J = 8.3 Hz, 1H),
(SiO , toluene/EtOAc = 9:1) led to 44 mg of 3 in 30 % yield as white
2
1
7
.69 (s, 1H), 7.66 (s, 1H), 7.63 (s, 1H), 7.56 (s, 2H), 7.50 (s, 1H), 7.42 solid powder. H NMR (400 MHz, CDCl ) 8.43 (s, 1H), 8.13 (d, J =
3
(d, J = 8.2 Hz, 1H), 7.39 (d, J = 8.2 Hz, 1H), 7.26 (dd, J = 8.2, 7.3 Hz,
8.3 Hz, 1H), 7.87 (d, J = 8.5 Hz, 1H), 7.84–7.82 (m, 1H), 7.79–7.77 (m,
1
6
1
2
7
1
1
H), 7.18 (dd, J = 8.2, 7.3 Hz, 1H), 7.05–7.01 (m, 2H), 6.38 (s, 1H),
.15 (t, J = 8.1 Hz, 1H), 6.08 (t, J = 8.1 Hz, 1H), 4.91 (t, J = 7.9 Hz,
1H), 7.70 (dd, J = 8.1, 7.0 Hz, 1H), 7.59 (dd, J = 7.6, 7.3 Hz, 1H), 7.49–
7.46 (m, 2H), 7.44 (s, 1H), 7.42 (s, 1H), 7.23 (s, 1H), 7.17 (s, 3H), 6.58
(s, 1H), 5.79–5.71 (m, 2H), 4.61 (t, J = 7.6 Hz, 1H), 4.49 (t, J = 7.6 Hz,
3
H), 4.75 (t, J = 7.9 Hz, 1H), 3.72 (d, J = 8.6 Hz, 3H, POCH ), 2.43–
PH
3
3
3
3
.32 (m, 8H), 2.04 (d, JPH = 12.4 Hz, 3H, POCH ), 1.48–1.29 (m,
2H), 0.95–0.93 (m, 12H) ppm; C{ H} NMR (100 MHz, CDCl ) 153.3, 2.24 (m, 8H), 1.41–1.28 (m, 72H), 0.92–0.87 (m, 12H) ppm; H NMR
1H), 4.00 (d, J = 11.3 Hz, 3H), 3.88 (d, J = 8.9 Hz, 3H), 2.36–
3
PH PH
1
3
1
1
3
53.23, 153.19, 153.1, 153.0, 152.9, 152.7, 152.4 (d, JC,P = 1.2 Hz),
48.8, 148.6 (d, JC,P = 6.2 Hz), 148.5, 147.3 (d, JC,P = 4.5 Hz), 146.6
(400 MHz, [D ]toluene) 8.82 (s, 1H), 7.98 (d, J = 8.2 Hz, 1H), 7.95 (s,
8
1H), 7.77 (s, 1H), 7.69–7.59 (m, 5H), 7.49 (s, 1H), 7.48 (d, J = 8.2 Hz,
1H), 7.26 (m, 2H), 7.16–6.93 (m, 2H), 7.61 (s, 1H), 6.20 (t, J = 8.0 Hz,
(d, JC,P = 2.4 Hz), 140.34, 140.31, 140.28, 140.2, 137.8 (d, JC,P =
Eur. J. Org. Chem. 2019, 6261–6268
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1
1
2
H), 6.11 (t, J = 8.0 Hz, 1H), 4.90 (t, J = 7.6 Hz, 1H), 4.77 (t, J = 7.6 Hz,
29.8, 29.7, 23.0 (many peaks are overlapped), 14.5 (many peaks are
3
3
31
1
H), 3.55 (d, J = 11.3 Hz, 3H), 3.45 (d, J = 8.9 Hz, 3H), 2.47–
overlapped) ppm; P{ H} NMR (162 MHz, CDCl ) 112.8, –7.60 ppm;
PH
PH
3
13
1
–
.29 (m, 8H), 1.33–1.28 (m, 72H), 0.96–0.92 (m, 12H) ppm; C{ H}
MS (ESI) m/z: 1760 [M + Cl] ; IR (neat): ν = 2921, 2849, 1483, 1408,
˜
–
1
NMR (100 MHz, CDCl ) 153.5, 153.3, 153.0, 152.8, 152.7, 147.6, 147.2 1328, 1145, 1041, 914, 759 cm ; HRMS (ESI) calcd. for
3
–
(d, JC,P = 3.8 Hz), 146.34, 146.28, 146.1 (d, JC,P = 6.91 Hz), 140.41,
C H AuCl N O P : 1759.7320 [M + Cl] , found 1759.7350.
90
118
2 4 11 2
1
1
1
1
3
40.38, 140.31, 140.27, 138.0, 137.2, 136.9 (d, JC,P = 1.9 Hz), 136.6,
35.8, 135.3, 134.4 (d, JC,P = 4.5 Hz), 133.0, 132.9, 129.7, 129.6, 129.4,
29.2, 128.7, 128.4, 128.24, 128.20, 123.6, 123.0, 122.5, 122.3, 119.3,
18.8, 117.03, 116.99, 116.93, 56.0 (d, JC,P = 6.2 Hz), 50.2, 36.0, 35.9,
4.5, 34.4, 33.1, 32.3, 32.1, 31.5, 31.4, 30.1 (many peaks are over-
Representative procedure for Au-catalyzed dimerization of ter-
minal alkynes: (see Scheme 3) Under N atmosphere, the bis-Au
2
catalyst (0.01 mmol) in a 25 mL two-necked flask was dissolved in
toluene (5 mL; containing traces of water), and the starting alkynes
of ethynylbenzene (102 mg, 1 mmol) and the other partner
lapped), 29.8 (many peaks are overlapped), 28.4, 28.3, 23.1 (many
peaks are overlapped), 14.5 (many peaks are overlapped) ppm;
1-octyne (165 mg, 1.5 mmol) were added. After addition of AgOTf
(5.0 mg, 0.02 mmol) at room temperature, the reaction was con-
31
1
P{ H} NMR (162 MHz, CDCl ) 125.7, –13.6 ppm; MS (ESI) m/z: 1528
3
ducted for 20 h. The solvent was evaporated off, and filtered
through a short-plugged column chromatography to give a crude
product. The crude materials consisted of just starting alkynes and/
or product 7a, 7b, and 7c because of clean reaction progress: thus,
chemical yields and molar ratios of products were determined in
the crude state. All dimer adducts were identical to the authentic
–
[
1
M + Cl] ; IR (neat): ν˜ = 2922, 2851, 1578, 1482, 1412, 1352, 1146,
–1
029, 760 cm ; HRMS (ESI) calcd. for C H N O P Cl: 1527.7966
90 118 4 11 2
–
[
M + Cl] , found 1527.7967.
Synthesis of 1·(AuCl)2 and 3·AuCl: (see Scheme 2) For 1·(AuCl)2:
Under N atmosphere, a solution of 1 (148 mg, 0.1 mmol) in toluene
2
[
10]
samples that we previously reported.
(2 mL) underwent addition of AuCl·S(CH ) (71 mg, 0.24 mmol), and
3 2
the mixture was stirred for 40 min, consumption of 1 was monitor-
ing by TLC. After all the volatiles had been evaporated, 174 mg of
Representative procedure for Au-catalyzed hydration of inter-
nal alkynes: (see Scheme 4) Complex 1·(AuCl) (17 mg, 0.01 mmol)
2
as white powder materials, corresponding to 1·(AuCl) complex was
2
was added under Ar to a solution of 3-octyne (0.07 mL, 0.5 mmol)
1
isolated in quantitative yield. H NMR (400 MHz, CDCl ) 8.33 (s, 1H),
3
in [D ]toluene (1 mL) and H O (0.05 mL, 2.5 mmol). The mixture
8
2
7
.92–7.90 (m, 4H), 7.64–7.58 (m, 4H), 7.46 (s, 2H), 7.31 (s, 1H), 7.29
was stirred at room temperature for 5 min, AgOTf (3 mg,
.012 mmol) was then added, and the whole system was immersed
(
7
(
s, 2H), 7.24 (s, 1H), 6.82 (s, 1H), 5.77 (t, J = 8.0 Hz, 2H), 4.44 (t, J =
0
3
.3 Hz, 2H), 4.02 (d, JP, H = 13.8 Hz, 6H), 2.30–2.17 (m, 8H), 1.45–1.27
in a 50 °C preheated oil bath. After stirred for 1 h, the reaction
mixture was cooled to ambient temperature. Purification by short-
plug silica-gel column chromatography with use of a Pasteur pi-
m, 72H), 0.90–0.87 (m, 12H) ppm; 13C{ H} NMR (100 MHz, CDCl )
1
3
1
1
53.2 (d, JC,P = 1.7 Hz), 153.1 (two peaks are overlapped), 152.2,
52.0, 145.3, 144.6, 140.2, 140.1 (two peaks are overlapped), 137.9
1
pette and [D ]toluene as eluent gave a colorless C D solution. H
8
7 8
(d, JC,P = 1.9 Hz), 137.0, 136.0, 135.7, 130.2, 130.0, 129.6, 127.5, 123.4,
NMR spectroscopy determined the chemical yields and product dis-
1
23.2, 119.0, 118.3, 55.1 (POCH ), 36.0, 34.4, 32.2 (many peaks are
[11] 1
3
tribution (proportions of 7f and 7g).
H NMR spectroscopic data
overlapped), 31.2, 30.0 (many peaks are overlapped), 29.9 (many
peaks are overlapped), 29.9, (many peaks are overlapped), 29.8, 29.7
for 7f and 7g were identical to those for commercially available
authentic sample.
(
many peaks are overlapped), 28.2, 28.1, 23.0, 22.9, 14.4 ppm;
Representative procedure for Rh-catalyzed hydroformylation of
styrene: (see Scheme 5) The hydroformylation reactions were car-
ried out in a glass-lined, 50 mL stainless steel autoclave containing
a magnetic stirring bar, then the autoclave was closed and flushed
3
1
1
P{ H} NMR (162 MHz, CDCl ) 99.4 ppm; MS (ESI) m/z: 1906
3
+
[
9
1
M - Cl] ; IR (neat): ν˜ = 2925, 2857, 1483, 1408, 1328, 1148, 1029,
–
1
05, 759, 599 cm ; HRMS (ESI) calcd. for C H Au ClN O P :
90 118 2 4 10 2
+
905.7343 [M - Cl] , found 1905.7394.
twice with vacuum/N . To the vessel were added toluene (8 mL),
2
For 3·AuCl: Under N2 atmosphere, a solution of 3 (111 mg,
.074 mmol) in toluene (1.2 mL) underwent addition of
styrene (10 mmol), n-decane (0.5 mL), 1 mL toluene solution of
0
Rh(acac)(CO) (2 μmol), and 1 mL toluene solution of appropriate
2
AuCl·S(CH3)2 (26 mg, 0.089 mmol), and the reaction mixture was
stirred for 30 min, consumption of 3 was monitoring by TLC. After
all the volatiles had been evaporated, the crude products were puri-
fied by short-plugged silica-gel column chromatography (eluent:
ligand. After pressurized at 20 bar (CO/H 1:1) and heated at appro-
2
priate temperature for the adequate time, the autoclave was cooled
to ambient temperature before being depressurized. The reaction
mixture was analyzed by GC using a WCOT fused-silica gel column
hexane/EtOAc, 1:1) to afford 56 mg of 3·AuCl as white powder ma-
1
chromatography (25 m × 0.25 mm) and by H NMR.
1
terials in 63 % yield. H NMR (400 MHz, CDCl ) 8.40 (s, 1H), 8.11 (d,
3
J = 8.4 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.78
Supporting Information (see footnote on the first page of this
d, J = 8.4 Hz, 1H), 7.72 (dd, J = 8.4, 8.4 Hz, 1H), 7.63 (dd, J = 8.4, article): 1H NMR and C NMR and P NMR spectra for all new
13
31
(
8
7
1
1
2
.4 Hz, 1H), 7.56 (s, 1H), 7.53–7.46 (m, 2H), 7.39 (s, 1H), 7.21 (s, 1H),
.20 (s, 1H), 7.19 (s, 1H), 7.15 (s, 1H), 6.73 (s, 1H), 5.81 (t, J = 8.0 Hz,
H), 5.77 (t, J = 8.3 Hz, 1H), 4.51 (t, J = 8.1 Hz, 1H), 4.50 (t, J = 8.2 Hz,
compounds of cis-1, cis-2, cis-3, 1·(AuCl) and 3·AuCl.
2
3
3
H), 4.07 (d, J = 13.9 Hz, 3H), 3.99 (d, J = 11.4 Hz, 3H), 2.36–
P, H
P, H
13
1
Acknowledgments
.21 (m, 8H), 1.48–1.27 (m, 72H), 0.90–0.87 (m, 12H) ppm; C{ H}
NMR (100 MHz, CDCl ) 153.6 (two peaks are overlapped), 153.1,
3
JSPS Grant-in-Aid for Scientific Research (C), Grant Number
9K05426, which supported T. I. in this work, is gratefully ac-
1
52.8 (two peaks are overlapped), 152.7, 152.5, 152.0, 146.8 (d, JC,P
=
1
6
.4 Hz), 146.3 (d, JC,P = 6.4 Hz), 144.3 (d, JC,P = 5.5 Hz), 143.8 (d,
knowledged for generous funding. The authors thank Dr. Toshi-
yuki Iwai and Dr. Takatoshi Ito at ORIST for gentle assistance
with HRMS. Prof. Dr. Schramm, M. P. at CSULB are gratefully
thanked for helpful discussions. S. H. gratefully acknowledges
the University of Carthage and the Tunisian Ministère de l′En-
JC,P = 4.8 Hz), 140.44, 140.36, 140.3, 140.2, 138.0 (d, JC,P = 1.7 Hz),
37.1 (d, JC,P = 4.8 Hz), 136.1, 135.9, 135.8, 135.5, 135.4, 133.6 (d,
JC,P = 3.6 Hz), 130.0, 129.9, 129.8, 129.7, 129.3, 128.8, 128.1, 127.8,
23.7, 123.0, 122.8, 122.5, 119.2, 118.4 (d, JC,P = 3.8 Hz), 117.0 (d,
1
1
2
2
JC,P = 4.3 Hz), 116.5, 56.0 (d, J = 6.0 Hz), 54.7 (d, J = 2.9 Hz),
C,P
C,P
3
6.0, 34.4, 33.2, 32.3 (many peaks are overlapped), 31.8, 30.4, 30.1 seignement Supérieur et de la Recherche Scientifique for finan-
(many peaks are overlapped), 30.0 (many peaks are overlapped), cial support.
Eur. J. Org. Chem. 2019, 6261–6268
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6267
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
[
[
8] F. Wöhler, Ann. Chim. Phys. 1828, 37, 330.
Keywords: Introverted ligands · Cavitands · Structure-
activity relationships · Homogeneous catalysis
9] a) T. Iwasawa, Y. Nishimoto, K. Hama, T. Kamei, M. Nishiuchi, Y. Kawamura,
Tetrahedron Lett. 2008, 49, 4758–4762; b) M. Kanaura, N. Endo, M. P.
Schramm, T. Iwasawa, Eur. J. Org. Chem. 2016, 4970–4975.
[
10] N. Endo, M. Kanaura, M. P. Schramm, T. Iwasawa, Eur. J. Org. Chem. 2016,
016, 2514–2521.
11] N. Endo, M. Inoue, T. Iwasawa, Eur. J. Org. Chem. 2018, 2018, 1136–1140.
[
1] a) R. Breslow, Acc. Chem. Res. 1995, 28, 146–153; b) P. D. Frischmann,
M. J. MacLachlan, Chem. Soc. Rev. 2013, 42, 871–890, and references
cited therein; c) P. Ballester, M. Fujita, J. Rebek Jr., Chem. Soc. Rev. 2015,
2
[
4
4, 392–393 and references cited therein.
[12] P. P. Castro, G. Zhao, G. A. Masangkay, C. Hernandez, L. M. Gutierrez-
[
2] a) R. J. Hooley, J. Rebek Jr., Chem. Biol. 2009, 16, 255–264, and references
cited therein; b) A. Galan, P. Ballester, Chem. Soc. Rev. 2016, 45, 1720–
Tunstad, Org. Lett. 2004, 6, 333–336.
No resonances of the “in-in” isomer was observed in the 1H NMR spec-
trum of the crude reaction mixture.
[13]
1737; c) D. M. Kaphan, F. D. Toste, R. G. Bergman, K. N. Raymond, J. Am.
Chem. Soc. 2015, 137, 9202–9205; d) M. Guitet, P. Zhang, F. Marcelo, C.
Tugny, J. Jimnez-Barbero, O. Buriez, C. Amatore, V. Mouris-Mansuy, J.-P.
Goddard, L. Fensterbank, Y. Zhang, S. Roland, M. Mnand, M. Sollogoub,
Angew. Chem. Int. Ed. 2013, 52, 7213–7218; Angew. Chem. 2013, 125,
[
14] The oxidation with mCPBA led to 24 % of di-phosphate derivative and
6 % of unreacted 1 was recovered.
4
[
15] In compound 5, crystallographic analysis revealed that, for steric reason,
8]
the two PN(CH
3
)
2
moieties point outside from the cavity, see ref.[
.
7354.
[
16] V. A. Azov, B. Jaun, F. Diederich, Helv. Chim. Acta 2004, 87, 449–462.
17] M. Inoue, K. Ugawa, T. Maruyama, T. Iwasawa, Eur. J. Org. Chem. 2018,
[
[
[
[
3] a) B. Cornils, W. A. Herrmann, Applied Homogeneous Catalysis with Orga-
nometallic Compounds, Wiley-VCH, Weinheim, Germany, 2nd Ed. 2002;
b) R. A. Sheldon, I. Arends, U. Hanefeld, Green Chemistry and Catalysis,
Wiley-VCH, Weinheim, Germany, 2007.
[
2
018, 5304–5311.
[18] a) See ref.[ ; b) S. Mosca, Y. Yu, J. V. Gavette, K.-D. Zhang, J. Rebek Jr., J.
Am. Chem. Soc. 2015, 137, 14582–14583; c) See ref.[ ; d) T. Iwasawa,
R. J. Hooley, J. Rebek Jr., Science 2007, 317, 493–496.
[19] M. P. Schramm, M. Kanaura, K. Ito, M. Ide, T. Iwasawa, Eur. J. Org. Chem.
2016, 2016, 813–820.
2b]
2c]
4] a) J. R. Moran, S. Karbach, D. J. Cram, J. Am. Chem. Soc. 1982, 104, 5826–
5
3
828; b) A. R. Renslo, J. Rebek Jr., Angew. Chem. Int. Ed. 2000, 39, 3281–
283; Angew. Chem. 2000, 112, 3419; c) T. Chavagnan, D. Sémeril, D.
Matt, L. Toupet, Eur. J. Org. Chem. 2017, 313–323.
5] a) Mini-reviews, A. C. H. Jans, X. Caumes, J. N. H. Reek, ChemCatChem
[
20] a) R. Bellini, S. H. Chikkali, G. Berthon-Gelloz, J. N. H. Reek, Angew. Chem.
Int. Ed. 2011, 50, 7342–7345; Angew. Chem. 2011, 123, 7480; b) V. Boco-
kic, A. Kalkan, M. Lutz, A. L. Spek, D. T. Gryko, J. N. H. Reek, Nat. Commun.
2019, 11, 287–297; b) Digest review: T. Iwasawa, Tetrahedron Lett. 2017,
5
8, 4217–4228; c) N. Natarajan, E. Brenner, D. Sémeril, D. Matt, J. Harrow-
field, Eur. J. Org. Chem. 2017, 2017, 6100–6113.
2
013, 4, No. 2670; c) M. Jouffroy, R. Gramage-Doria, D. Armspach, D.
Sémeril, W. Oberhauser, D. Matt, L. Toupet, Angew. Chem. Int. Ed. 2014,
3, 3937–3940; Angew. Chem. 2014, 126, 4018.
21] a) D. Sémeril, C. Jeunesse, D. Matt, L. Toupet, Angew. Chem. Int. Ed. 2006,
5, 5810–5814; Angew. Chem. 2006, 118, 5942; b) D. Sémeril, D. Matt, L.
Toupet, Chem. Eur. J. 2008, 14, 7144–7155; c) D. Sémeril, D. Matt, L. Tou-
pet, W. Oberhauser, C. Bianchini, Chem. Eur. J. 2010, 16, 13843–13849.
22] a) M. E. Broussard, B. Juna, S. G. Train, W.-J. Peng, S. A. Laneman, G. G.
Stanley, Science 1993, 260, 1784–1788; b) D. A. Aubry, N. N. Bridges, K.
Ezell, G. G. Stanley, J. Am. Chem. Soc. 2003, 125, 11180–11181; c) D. G. H.
Hetterscheid, S. H. Chikkali, B. de Bruin, J. N. H. Reek, ChemCatChem
6] From the viewpoint of supramolecular catalysis through encapsulation
effects, the following papers are relevant reviews, see a) T. S. Koblenz, J.
Wassenaar, J. N. H. Reek, Chem. Soc. Rev. 2008, 37, 247–262; b) M. Yoshi-
zawa, J. K. Klosterman, M. Fujita, Angew. Chem. Int. Ed. 2009, 48, 3418–
5
[
[
4
3
438; Angew. Chem. 2009, 121, 3470; c) M. J. Wiester, P. A. Ulmann, C. A.
Mirkin, Angew. Chem. Int. Ed. 2011, 50, 114–137; Angew. Chem. 2011,
23, 118; d) T. R. Cook, V. Vajpayee, M. H. Lee, P. J. Stang, K. W. Chi, Acc.
1
Chem. Res. 2013, 46, 2464–2474; e) M. Raynal, P. Ballester, A. Vidal-Ferran,
P. W. N. M. van Leeuwen, Chem. Soc. Rev. 2014, 43, 1734–1787; f)
S. H. A. M. Leenders, R. Gramage-Doria, B. de Bruin, J. N. H. Reek, Chem.
Soc. Rev. 2015, 44, 433–448; g) C. J. Brown, F. D. Toste, R. G. Bergman,
K. N. Raymond, Chem. Rev. 2015, 115, 3012–3035; h) D. Zhang, A. Marti-
nez, J.-P. Dutasta, Chem. Rev. 2017, 117, 4900–4942.
2013, 5, 2785–2793.
[
7] F. Diederich, Angew. Chem. Int. Ed. 2007, 46, 68–69; Angew. Chem. 2007,
1
19, 68.
Received: July 20, 2019
Eur. J. Org. Chem. 2019, 6261–6268
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© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim