Introverted Phosphorus-Au Cavitands for Catalytic Use

Article abstract of DOI:10.1002/ejoc.201501426

A preparative synthesis of an inwardly directed phosphoramidite-Au complex is described and a description of some of its catalytic performance. The molecular structure was determined by crystallographic analysis, which disclosed that the phosphoramidite ligand points “out” and places the complexed Au “in”. We investigated its catalytic activities and found that the inwardly directed Au is surrounded by three inert walls that provide new opportunities for supramolecular catalysis and study of reactive intermediates.

Full text of DOI:10.1002/ejoc.201501426

DOI: 10.1002/ejoc.201501426
Full Paper
Catalytic Cavitands
Introverted Phosphorus-Au Cavitands for Catalytic Use
[a]
[b]
[b]
[b]
Michael P. Schramm, Mao Kanaura, Kouhei Ito, Masataka Ide, and
Tetsuo Iwasawa*[
b]
Abstract: A preparative synthesis of an inwardly directed phos- Au “in”. We investigated its catalytic activities and found that
phoramidite-Au complex is described and a description of some the inwardly directed Au is surrounded by three inert walls that
of its catalytic performance. The molecular structure was deter- provide new opportunities for supramolecular catalysis and
mined by crystallographic analysis, which disclosed that the study of reactive intermediates.
phosphoramidite ligand points “out” and places the complexed
Introduction
Recently, we have reported the synthesis of introverted func-
tionality tethered to a cavitand scaffold of triquinoxaline-
[
16]
Natural receptors like enzymes and RNA strands have their spanned resorcin[4]arene 1 (Scheme 1) with dialkylsilanes
[
17]
functional groups oriented inwards for molecular recogni- and allylsilanes.
The introverted allyl cavitand enabled us to
Amino acid functional groups converge to create react- realize that it has higher reactivity than the extroverted one
[
1,2]
tion.
ive sites inside the hydrophobic pockets, and the grooves of toward meta-chloroperoxybenzoic acid (mCPBA). Such a supra-
nucleic acids are also concave and lined with convergent func- molecular effect drove us to develop a new pyridine N-oxide
tionality to fold around guest substrates. Thus they serve as cavitand as a supporting ligand in transition metal catalyzed
[
18]
incredibly well-organized chemical catalysts to perform numer- reactions, but N-oxide was unsuccessful in a variety of other-
[
3]
ous biological operations. Inspired by these, organic chemists wise straightforward catalytic transformations. We thus have fo-
have developed artificial receptors that bear functional substit- cused our attention on supramolecular frameworks that would
[
4–6]
uents inside chemical space.
Such an inwardly directed “in- support an inwardly located metal center for improving chemi-
troverted” functional group is a form of synthetic receptor origi- cal transformations.
nally designed by Rebek, in which a reactive site converges
[
7]
onto a concave surface of resor[4]arene-based cavitand. The
Rebek group has deployed these introverted functionalized cav-
itands as beautiful tools to understand facets of bio-relevant
[
8–11]
reactions;
however, introverted functional groups have not
developed into a powerful synthetic platform. Two shortcom-
ings provide chemists a continuing challenge. The first problem
is the synthetic difficulty to prepare even 100 mg of functional-
[
12]
ized cavitands.
The second is hardships in the synthesis of
cavitand/organometal hybrids in which introverted functional-
ity acts as a supporting ligand to make a complex with transi-
[
13]
tion metals.
Overcoming these two drawbacks perhaps will
Scheme 1. Triquinoxaline-spanned resorcin[4]arene 1.
allow cavitands to make more significant inroads in the syn-
thetic community, and a properly built hybrid may one day
Herein we report the preparative synthesis of hybrid com-
work as a real tool for new modes of chemical catalysis and plex 3, the result of a simple reaction between phosphoramid-
[
14,15]
discovery.
ite 2 and AuCl·S(CH
prepared (2.3 g scale) as one of two possible isomers (“in” or
out”) in one step from 1. Upon reaction of 2 with AuCl·S(CH ) ,
3 2
) (Scheme 2). Compound 2 was readily
“
3
2
[
[
a] Department of Chemistry and Biochemistry, California State University
new complex 3 was prepared quantitatively. Its X-ray structural
analysis unveiled the previously unconfirmed orientation of
phosphoramidite moiety of 2, and the ORTEP figure reveals the
details of an inwardly directed Au that resides inside the cavity.
Thus, bulky 2 was selectively installed in an outward position
with its electrons pointing inward. The potential of this complex
is significant; Au is located inward, flanked by three walls of
“organized solvent”.
Long Beach (CSULB),
250 Bellflower Blvd. Long Beach, Los Angeles, CA 90840, USA
https://schrammlab.wordpress.com/
1
b] 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
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201501426.
Eur. J. Org. Chem. 2016, 813–820
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3 2
Scheme 2. Preparative synthesis of introverted phosphoramidite 2 from 1, and subsequent complexation with AuCl·S(CH ) to give 3.
Analogously, we synthesized two other phosphorus cavi-
tands with variation to the external phosphorus substituent.
Finally, we found that the Au–Cl complexes reported herein
I
have catalytic activity consistent with Au ; addition of water to
terminal alkynes and cyclization of diketo-alkynes occurs. These
initial results set the stage to explore the consequences of a
I
new inwardly directed Au catalytic center, surrounded by three
solvent walls. The trapping of reactive intermediates and size
exclusion of substrates and intermediate stabilization are tanta-
[
19]
lizing possibilities that drive this work.
Results and Discussion
Phosphorus 2 was reported in 2008 from our group.[16] On a
0
.1 mmol scale, 89 mg of 2 was isolated (57 % yield), the iso-
[
20,21]
meric ratio was about 95:5.
The stereochemical outcome
was assumed to place the amine group outwards. By revisiting
this reaction we could successfully isolate one major isomer on
a
2.3-gram scale (short-plug, CH Cl ). Reaction with
2 2
2 2
Figure 1. ORTEP drawing of 3·CH Cl with thermal ellipsoids at the 50 %
probability level; (a) top view; (b) side view; (c) side view of 3 with interior
AuCl·S(CH3)2 gave quantitative formation of Au cavitand 3
Scheme 2). The molecular structure of 3 was determined by
crystallographic analysis, which disclosed the introverted Au ar-
(
CH Cl omitted for clarity. Hydrogen atoms are omitted for clarity. Selected
2
2
bond lengths [Å]: P–Au 2.196, Au–Cl 2.303, P–N 1.622.
[
22]
rangement (Figure 1).
Several crystals were grown and, in
the one reported, we find a molecule of CH Cl in the interior,
2
2
sandwiched between gold and the cavitand walls, see Figure 1
1
(
a and b). The H NMR spectrum of 3 showed a single con-
former; for example, a dimethyl group of -PN(CH ) gave just
3
2
3
one peak at 3.07 ppm (d, J = 12.9 Hz, 6 H) in CDCl3.
PH
In a similar fashion, methoxy phosphite 3-walled cavitand 4
was prepared from 1 by reaction with P(OCH3)3 (Scheme 3).
Silica gel column chromatography was sufficient to isolate the
two isomers that formed; outwardly directed 4a was isolated in
5
7 % yield, and inward 4b in 21 % yield. The methyl group of
3
CH OP 4a in CDCl is located at δ = 3.92 ppm (d, J = 8.3 Hz),
and in 4b is shifted to upfield 2.99 ppm (d, J = 12.4 Hz) due
to the anisotropic effect of the π electron-clouded space.
Subsequent complexation of 4a with AuCl·S(CH ) gave 5 in
3
3
PH
3
PH
[
16]
3
3
quantitative yield. We were unable to collect crystals of suitable
quality for X-ray analysis, but from the in-out anisotropy ob-
served in 4a versus 4b we have made confidently our stereo-
chemical assignment of 5.
In a final example, phenyl phosphonite 6 was prepared in
Scheme 3. (a) Synthesis of intro- and extroverted phosphite 4; (b) complexa-
60 % isolated yield as a single isomer (as determined by NMR
3 2
tion of 4a with AuCl·S(CH ) to give 5.
Eur. J. Org. Chem. 2016, 813–820
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3 2
Scheme 4. Selective synthesis of introverted phosphonite 6, and subsequent complexation with AuCl·S(CH ) to give 7.
spectroscopy)[21] from reaction of 1 with PhP[N(CH CH ) ]
strate the vase is preferred. Some variation exists and the differ-
Scheme 4). The reaction of 6 and AuCl·S(CH3)3 successfully ences observed between chlorinated to aromatic solvents are
2
3 2 2
(
[
23]
gave complex 7 in 88 % yield. For complex 7 (and correspond- consistent with previous observations.
For 3, we see nearly
ing 6) the chemical shifts of the phenyl group show no indica- identical behavior of the methines relative to parent 2. No ma-
tion of upfield shifts and thus it is reasonable to assume that jor perturbations to structure are observed and the molecule is
a
b
the group is outwardly directed, whereas Au is inwardly di- well behaved with sharp methines; H and H protons are con-
rected. The chemical shifts of the resorcin[4]arene bridging me- sistent in all solvents with a vase shape. The latter observation
thines for 7 are consistent with those for 5 and 3. From these coupled with solid-state evidence supports the idea that the
results it appears that the larger size of dimethylamine (for 2) metal center is pointing inwardly in solution.
or phenyl (for 6) direct the stereochemical outcome of the reac-
tion. The smaller methoxy (see 4a and 4b) afforded appreciable ety of recent reviews on the subject of Au-catalyzed reactions
We next took 3 and examined it for catalytic activity. A vari-
[
24]
amounts of stereoisomers.
exist.
These served as inspiration for our initial screenings;
Before reporting on our catalytic results, we make the follow- hydration of terminal alkynes, and Conia-ene reaction of ꢀ-keto
ing observations about the solution dynamics of 3. 4-Walled ester alkynes were adopted. For hydration of terminal alkynes,
quinoxaline cavitands are known to fluctuate between vase we attempted a simple hydration reaction by following reports
I [25]
(
closed) and kite (open) conformations and reports on the ef- with Au .
We first began by mixing ethynylbenzene with 3
[
23]
1
fects of solvent and acid are known.
Typically, methine pro- (Figure 2). After 24 h, the H NMR spectrum showed that the
tons around δ = 5.5 ppm are indicative of vase conformers, alkyne and 3 were unreacted [Figure 2(b)]. Addition of AgOTf
whereas δ = 3.7 ppm indicates the kite form. For 2 in Table 1, [Figure 2(c)] and waiting for 2 h nearly eliminated all traces of
c
proton H is in a different electronic environment than the other
a
b
a
b
two protons H and H . H and H in all solvents clearly demon-
a
c
Table 1. NMR chemical shifts of the methine protons H –H of 2 and 3.
Solvent
CD Cl
CDCl
Ha
Hb
Hc
Ha′
Hb′
Hc′
2
2
5.32
5.68
6.10
6.04
6.01
5.66
5.68
6.20
6.12
6.06
–
4.57
4.54
5.13
5.02
4.93
–
5.64
5.70
6.07
6.05
5.97
(5.78)
5.76
5.76
6.18
6.09
4.55
4.53
4.75
4.74
4.72
–
3
Figure 2. Up- and downfield portion of the 1H NMR (400 MHz, [D
]toluene)
8
[D
[D
[D
[D
6
]benzene
]toluene
10]-p-xylene
spectra for (a) ethynylbenzene (0.019 mmol); (b) 33 mol-% 3 added and left
at room temp. for 24 h; (c) 42 mol-% AgOTf added and left at room temp.
for 2 h; (d) 6 equiv. of water added and heated to 85 °C for 1 h; and (e) heated
for 40 h. Each resonance labeled with T, black circle, and white circle corre-
8
6.03
[
a]
[a]
(5.54)[a]
12]mesitylene (5.82)
[
a] Peaks were broadened, but small averaged peaks could be observed.
www.eurjoc.org
sponds to residual C
7
H
8
, ethynylbenzene, and acetophenone, respectively.
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3
from the solution spectra. Small non-descript features remain,
and a very slight trace of a new species emerges at δ ≈
.68 ppm. Next, an excess of water was added and the reaction
Table 2. Results of the catalytic hydration of terminal aromatic alkynes.[a]
7
was heated to 85 °C, after which the concentration of ethynyl-
benzene drastically decreased with a concomitant increase in
[
26,27]
the formation of benzophenone [Figure 2(d)].
heating for 40 h resulted in more hydration of alkyne to ketone
Figure 2(e)]. However, black metal residues were gradually ob-
Continued
Entry
R
X
Solvent
Conversion[b]
.5 h
[
1
19 h
served; thus, the Au atom can leave the parent ligand and the
Au complex might decompose.
1
2
3
4
5
6
7
8
Ph
Ph
OTf
OTf
OTf
OTf
OTf
OTf
SbF
[D
[D12]mesitylene
[D ]toluene
[D12]mesitylene
[D ]toluene
[D12]mesitylene
8
]toluene
15 %
14 %
4 %
43 %[c]
49 %
48 %[
16 %
100 %
98 %
49 %
4 %
c]
To confirm the identity of the active species we changed the
1-naphthyl
1-naphthyl
9-anthryl
9-anthryl
Ph
8
[
28]
5 %
order of addition (Figure S1), ethynylbenzene was first mixed
with AgOTf and no reaction was observed. Addition of water
and heating also resulted in intact material. Finally the addition
of 5 mol-% 3 with heating resulted in the formation of benzo-
phenone. After an additional 12 h of heating there was low
total conversion to benzophenone (12 %), with 83 % of starting
alkyne remaining. At the time the reaction remained unopti-
mized but the results demonstrated the need of both Au and
Ag species. Neither species catalyzes the reaction on its own
and the observation in the disappearance of cavitand peaks
when 3 was treated with AgOTf [Figure 2(b) versus (c)] supports
an Au cationic species as being the active catalyst. Furthermore,
HRMS (MALDI-TOF) of 3 gives three major ions in decreasing
81 %[
54 %
4 %
c]
8
6
[D
[D
8
]toluene
]toluene
Ph
BF
4
8
3 %
[
2
a] Substrate (0.056 mmol), H O (0.056 mmol), 3 (5 mol-%), AgX (5 mol-%),
and solvent (0.55 mL). [b] Conversion = integration of product protons di-
vided by normalized total area of substrate and product. No other major
1
peaks were observed. [c] Representative H NMR spectrum is included in the
Supporting Information.
naphthalene-H δ = 3.48 ppm, 9-ethynylanthracene-H δ =
4
.00 ppm). The last species is unstable when stored.
Gold 3 shows more promise for aliphatic alkynes (Table 3).
+
+
+
order of intensity: [3 – Cl] , [3 + 2H] , [3 + Na] . The major ion 1-Hexyne is completely converted into 2-hexanone in less than
is from ready loss of “Cl” under ionizing conditions, which at- 1 h with heating (Table 3, Entry 1). The reaction in CDCl
was
3
+
tests to the ease of Au formation. When 3 was mixed with an sluggish and incomplete (Table 3, Entry 2). Increasingly bulky
equal molar amount of AgOTf in CH Cl for 15 min then ana- alkynes, such as 4-phenyl-1-butyne and tert-butylacetylene, also
2
2
+
+
+
lyzed by MS, no evidence of [3] , [3 + H] or [3 + Na] species showed good conversion (Table 3, Entries 3 and 4). These latter
+
was observed, instead [3 – Cl] was the only identifiable two alkynes had similar reactivity profiles to each other, and
[
29]
peak.
Based on NMR and MS data, cationic Au formation by the reaction is only half complete after 1 h and requires 16 h
“
3 – Cl” is envisioned as the active catalyst species.
to approach good conversion. With these results we predict
future application of 3 may include size-selective reactivity. At
this time, however, the cavitand does not have significant se-
lective ability, but these studies are the beginning of our explo-
ration.
We optimized the conditions for the hydration of aromatic
terminal alkynes by mixing 5 mol-% each of 3 and AgOTf and
heating for 30 min, which resulted in an active catalyst species
(
Table 2). Upon addition of water and alkynes and heat for 1.5 h,
we noted conversion under several conditions. Final measure-
ments were made at 19 h. We find ethynylbenzene is converted
slowly and in modest final yield of acetophenone (Table 2, En-
tries 1 and 2). By moving to the more bulky 1-ethynylnaphth-
alene the results mimic those for ethynylbenzene (Table 2, En-
try 3). When mesitylene was substituted as the solvent the re-
sults were disappointing ( Table 2, Entry 4). This is interesting
because mesitylene is widely reported to be too large to oc-
cupy the internal space. Indeed, NMR spectroscopic analysis in
mesitylene of the cavitand species is difficult (Table 1). In this
instance we expected toluene would compete for the catalytic
site better and perhaps mesitylene would result in improved
yields, but the opposite was true. We moved to 9-ethynylan-
thracene (Table 2, Entries 5 and 6),[ whereas the bulk of the
substrate has increased drastically, so too has the reactivity of
the alkyne.
Table 3. Results of the catalytic hydration reaction of terminal aliphatic
alkynes.[a]
Entry
R
Solvent
Conversion[b]
1
h
4 h
16 h
1
2
3
4
CH
CH
Ph(CH2)2
(CH
3
(CH
(CH
2
2
)
)
3
[D
CDCl
[D ]toluene
8
]toluene
100 %
25 %
52 %
49 %
–
–
3
3
3
(65 °C)
26 %
72 %
67 %
29 %
79 %
89 %
8
3
)
3
C
8
[D ]toluene
30]
[a] Substrate (0.056 mmol), H O (0.056 mmol), 3 (5 mol-%), and solvent
2
(0.55 mL). [b] Conversion = integration of product protons divided by normal-
ized total area of substrate and product. No other major peaks were ob-
served.
Aromatic alkynes have two competing factors for reactivity
with 3, size and electronics. These factors for the three sub-
Next, we examined the ability of 3 to catalyze Conia-ene
strates are inversely related. Downfield shifts of the alkyne pro- reactions (Table 4).[31,32] We were inspired by this work as an
ton reveal information about the electronic character of the entry point to test the substrate size, solvent effects of the cavi-
alkyne (in CDCl ; ethynylbenzene-H δ = 3.07 ppm, 1-ethynyl- tand scaffold, and the effect of the ligand in 3, 5, and 7. Brief
3
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heating of Au and Ag in deuterated solvent followed by subse- best guest. Au plays a special role in this first instance; it has
quent treatment with 8 and further heating resulted in product robust and important reactivity that can be tuned directly
formation. The catalytic conversion of 8 to 9 was easy to follow through the ligand set. There are many more variations of reac-
by NMR spectroscopy, with several chemically distinct protons. tions to try. In these endeavors we look forward to reporting
After 1 h of heating we identified 9 in 10 % conversion (Table 4, on supramolecular advantages of this easily accessed chemical
Entry 1), with 65 % of remaining 8. The 25 % of material was platform.
1
0 that resulted from direct hydration of the terminal alkyne.
Despite not adding water, adventitious water appears to be in-
corporated into the triple bond. Compound 9 is known, and 10
was isolated and characterized by H NMR spectroscopy (see
Experimental Section
1
Supporting Information). The reaction was allowed to heat and General Methods: All reactions sensitive to air or moisture were
carried out under an argon atmosphere and anhydrous conditions.
Dry solvents were purchased and used without further purification
and dehydration. All reagents were used as received. Analytical thin
layer chromatography was carried out on Merck silica 60F254. Col-
resulted in an equal distribution of 8, 9, and 10. By changing
solvent to CDCl (Table 4, Entry 2) we found that after 1 h, 10
3
was the major new species formed, but at 17 h, 62 % of the
total material was 9. At this stage we decided to analyze the
differences between 3, 5, and 7. After initial studies, it appears
there is an advantage to the use of the P–N 3. Indeed P–Ph and
P–OMe ligands left much of 8 unreacted after 17 h (Table 4,
Entries 3 and 4). This result has not been fully explored, but it
umn chromatography was carried out with silica gel 60
N (Kanto
Chemical Co.). HRMS were reported on the basis of TOF (time of
flight), and EB (double-focusing) techniques. 1H and C, and
13
31
P
NMR spectra were recorded with a 5 mm QNP probe at 400, 100,
and 162 MHz, respectively. Chemical shifts are reported to residual
1
is easy to envision P–N provides an added degree of electron solvent signals ( H NMR: CHCl δ = 7.26, C H δ = 2.08, C H δ =
3
7
8
6 6
δ = 5.32; 13C NMR: CDCl
δ = 77.0). Signal patterns are
donation into the P center.
7.16, CH
2
Cl
2
3
indicated as s for singlet, d for doublet, t for triplet, q for quartet,
m for multiplet, br. for broad.
Table 4. Results of Conia-ene reactions of 8.[a]
Gram-Scale Synthesis of Phosphoramidite 2: (see Scheme 2) Un-
der an N atmosphere, to a three-necked 300 mL flask charged with
2
_
triquinoxaline-spanned resorcin[4]arene 1 (5.34 g, 3.6 mmol) and
dry toluene (72 mL) in a pre-heated 75 °C oil bath was added Et N
3
(1.2 mL, 8.6 mmol). Then, tris(dimethylamino)phosphine (0.77 mL,
4.3 mmol) was added. After stirring for 1.5 h, complete consump-
tion of the starting resorcin[4]arene was ensured by TLC monitoring
and the reaction mixture was cooled to ambient temperature. The
mixture was filtered through a pad of Celite, and the filtrate was
concentrated in vacuo to give 5.82 g of yellow solid compounds.
Entry Catalyst
Solvent
Temp.)
Time
8[b]
9[b]
10[b]
(
1
3
[D ]toluene
85 °C)
8
1 h
2.5 h
65 %
53 %
35 %
69 %
17 %
72 %
55 %
75 %
42 %
10 %
20 %
34 %
3 %
62 %
3 %
23 %
2 %
25 %
25 %
26 %
33 %
20 %
28 %
23 %
25 %
23 %
33 %
Purification by short-plug column chromatography (CH Cl ) af-
forded 2.64 g of 2 in 41 % yield as a white solid. H NMR (400 MHz,
2 2
1
(
1
7 h
CDCl ): δ = 8.31 (s, 2 H), 8.01 (d, J = 8.3 Hz, 2 H), 7.74–7.70 (m, 4
3
2
3
4
3
5
7
CDCl
3
1 h
17 h
1 h
17 h
1 h
17 h
H), 7.59 (dd, J = 8.3, 8.3 Hz, 2 H), 7.49 (dd, J = 8.3, 8.3 Hz, 2 H), 7.39
(
60 °C)
(
dd, J = 6.1, 3.3 Hz, 2 H), 7.23 (s, 2 H), 7.21 (s, 2 H), 7.19 (s, 2 H), 5.68
CDCl
3
3
(t, J = 8.2 Hz, 3 H), 4.54 (t, J = 7.7 Hz, 1 H), 2.78 (d, J = 10.7 Hz,
PH
(
60 °C)
6
H), 2.27–2.18 (m, 8 H), 1.58–1.28 (m, 72 H), 0.90–0.87 (m, 12
CDCl
3
1
H) ppm. H NMR (400 MHz, CD Cl ): δ = 8.24 (s, 2 H), 7.97 (d, J =
2
2
(
60 °C)
a] Compound 8 (0.056 mmol), H
b] Conversion = integration of product protons divided by normalized total
7
(
7
.7 Hz, 2 H), 7.76–7.73 (m, 4 H), 7.63 (dd, J = 7.7, 7.7 Hz, 2 H), 7.54
dd, J = 7.7, 7.7 Hz, 2 H), 7.47 (dd, J = 6.2, 3.4 Hz, 2 H), 7.31 (s, 2 H),
.26 (s, 2 H), 7.19 (s, 2 H), 5.67–5.64 (m, 3 H), 4.57 (t, J = 8.6 Hz, 1
[
[
2
O (0.056 mmol), and solvent (0.55 mL).
area of substrate and product. No other major peaks were observed.
3
H), 2.78 (d, J = 10.5 Hz, 6 H), 2.32–2.22 (m, 8 H), 1.47–1.29 (m, 72
H), 0.91–0.88 (m, 12 H) ppm. H NMR (400 MHz, [D ]toluene): δ =
PH
1
8
8
.69 (s, 2 H), 7.84 (dd, J = 5.9, 3.7 Hz, 2 H), 7.71–7.69 (m, 2 H), 7.69
s, 2 H), 7.64 (s, 2 H), 7.61 (s, 2 H), 7.39 (d, J = 8.2 Hz, 2 H), 7.20 (dd,
J = 5.9, 3.7 Hz, 2 H), 7.09–7.00 (m, 4 H), 6.12 (t, J = 8.1 Hz, 1 H), 6.04
(
Conclusions
3
In summary, the arrangement of an Au atom, which points in- (t, J = 8.1 Hz, 2 H), 5.01 (t, J = 7.7 Hz, 1 H), 2.54 (d, J = 10.2 Hz,
PH
ward and is flanked by 3 aromatic walls, provides a new archi- 6 H), 2.50–2.41 (m, 8 H), 1.33–1.31 (m, 72 H), 0.96–0.93 (m, 12
H) ppm. 13C NMR (100 MHz, CDCl ): δ = 153.1, 153.0, 152.9, 152.7,
152.5, 152.2, 149.5 (d, JCP = 4.8 Hz), 139.92, 139.89, 139.8, 137.1,
tecture for catalysis. This result differs from the first discoveries
3
[
10(a),14]
in the field
in which the inwardly directed functionality
1
1
36.3, 136.0, 134.4, 129.3, 129.0, 128.8, 128.03, 128.00, 127.9, 123.5,
22.5, 119.1, 117.3, 35.8, 35.2 (d, JCP = 18.2 Hz), 34.3, 34.2, 33.0, 32.1
was organic in nature and blocked access to the concave sur-
[
13]
face. A Pd-bound cavitand is known
ties for directing the metal center truly inward. The case of 3,
, and 7 differs from these archetypes: the top of the catalytic
site remains open so that guests can sample the space, enter
but has fewer proclivi-
(
2
peaks overlap), 31.7, 29.9 (peaks overlap), 29.6 (peaks overlap),
31
8.2, 28.1, 22.9 (peaks overlap), 14.3 (peaks overlap) ppm. P NMR
5
31
(162 MHz, CDCl ): δ = 141.0 ppm. P NMR (162 MHz, CD Cl ): δ =
3
2
2
31
1
41.0 ppm. P NMR (162 MHz, [D ]toluene): δ = 138.7 ppm. MS
8
–
and leave. Au cavitands are also less likely to be complicated (ESI): m/z = 1591 [M + Cl] . C H N O P (1557.06): calcd. C 75.60,
9
8 122 7 8
by product inhibition, in which the product itself becomes the H 7.90, N 6.30; found C 75.38, H 7.86, N 6.34.
817 © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2016, 813–820
www.eurjoc.org

Full Paper
Au Complex 3: (see Scheme 2) Under an N atmosphere, to a solu-
135.4, 129.6, 129.4, 129.2, 128.6, 128.2, 128.1, 123.7, 123.0, 119.4,
2
tion of 2 (156 mg, 0.1 mmol) in anhydrous CH Cl (3 mL) at ambient
117.8, 50.4 (d, JCP = 4.1 Hz), 36.1, 34.5, 34.4, 33.1, 32.3 (peaks over-
2
2
temperature was added AuCl·S(CH ) (44 mg, 0.15 mmol). After stir- lap), 32.0, 30.1 (peaks overlap), 29.7 (peaks overlap), 28.4 (peaks
3
2
3
1
ring for 30 min, 1 had been consumed (TLC monitoring). The reac- overlap), 23.1 (peaks overlap), 14.5 (peaks overlap) ppm. P NMR
tion mixture was concentrated in vacuo to give a crude product in
31
(162 MHz, CDCl ): δ = 127.2 ppm. P NMR (162 MHz, [D ]toluene):
3
8
1
96 mg as a white solid. Purification by short-plug column chroma-
δ = 125.1 ppm. IR (neat): ν = 2921, 2851, 1605, 1578, 1482, 1400,
˜
1
–1
tography yielded 177 mg of 3 in 99 % as a white solid. H NMR
400 MHz, CDCl ): δ = 8.12 (s, 2 H), 7.85 (d, J = 8.1 Hz, 2 H), 7.80 (d,
1332, 1273, 1157, 1029, 895, 757 cm . MS (MALDI-TOF): m/z = 1544
+
(
([M + H] ). HRMS (MALDI-TOF): calcd. for C H N O P 1543.8849
3
97 120 6 9
+
J = 8.1 Hz, 2 H), 7.76 (dd, J = 6.1, 3.4 Hz, 2 H), 7.53–7.45 (m, 6 H),
[M + H] ; found 1543.8983. C H N O P (1544.02): calcd. C 75.46,
97 119 6 9
1
7
.39 (s, 2 H), 7.26 (s, 2 H), 7.25 (s, 2 H), 5.76 (t, J = 8.4 Hz, 1 H), 5.70 H 7.77, N 5.44; found C 75.26, H 7.69, N 5.27. For 4b. H NMR
(t, J = 8.1 Hz, 2 H), 4.54 (t, J = 8.1 Hz, 1 H), 3.09 (d, JPH = 13.0 Hz, 6
(400 MHz, CDCl ): δ = 8.28 (s, 2 H), 7.98 (d, J = 8.2 Hz, 2 H), 7.77
3
H), 2.33–2.30 (m, 8 H), 1.45–1.28 (m, 72 H), 0.90–0.87 (m, 12 H) ppm.
(dd, J = 6.2, 3.5 Hz, 2 H), 7.62 (d, J = 8.2 Hz, 2 H), 7.57 (dd, J = 8.2,
8.2 Hz, 2 H), 7.49–7.43 (m, 4 H), 7.22 (s, 2 H), 7.18 (s, 2 H), 7.15 (s, 2
1
H NMR (400 MHz, CD Cl ): δ = 8.18 (s, 2 H), 7.96 (dd, J = 6.4, 3.4 Hz,
2
2
2
4
5
1
1
H), 7.74–7.72 (m, 4 H), 7.66 (dd, J = 6.4, 3.4 Hz, 2 H), 7.51–7.44 (m,
H), 7.36 (s, 2 H), 7.29 (s, 2 H), 7.27 (s, 2 H), 5.75 (t, J = 8.3 Hz, 1 H),
H), 5.72 (t, J = 8.0 Hz, 1 H), 5.66 (t, J = 8.2 Hz, 2 H), 4.47 (t, J =
3
7.9 Hz, 1 H), 2.99 (d, J = 12.4 Hz, 3 H), 2.27–2.20 (m, 8 H), 1.43–
PH
.63 (t, J = 8.1 Hz, 2 H), 4.55 (t, J = 8.3 Hz, 1 H), 3.07, (d, 3JPH
=
1.28 (m, 72 H), 0.90–0.87 (m, 12 H) ppm. C NMR (100 MHz, CDCl3):
13
2.9 Hz, 6 H), 2.35–2.01 (m, 8 H), 1.45–1.30 (m, 72 H), 0.91–0.88 (m,
δ = 153.3, 153.2, 153.1, 153.0, 152.9, 152.2 (d, JCP = 1.4 Hz), 148.7
(d, JCP = 15.1 Hz), 140.14, 140.13, 140.09, 136.4, 135.4 (d, JCP =
1
2 H) ppm. H NMR (400 MHz, C D ): δ = 8.73 (s, 2 H), 8.03–8.00
6
6
(
2
m, 4 H), 7.76 (s, 2 H), 7.71 (d, J = 8.4 Hz, 2 H), 7.65 (s, 2 H), 7.64 (s,
H), 7.32 (dd, J = 6.2, 3.5 Hz, 2 H), 7.11 (ddd, J = 8.4, 7.0, 1.3 Hz, 2
H), 7.00 (ddd, J = 8.4, 7.0, 1.3 Hz, 2 H), 6.18 (t, J = 8.2 Hz, 1 H), 6.07
1.2 Hz), 134.8, 129.7, 129.3, 129.2, 128.3, 128.2, 127.8, 124.1, 122.5,
119.2, 117.4, 51.7 (d, JCP = 22.2 Hz), 36.8, 34.5, 34.4, 33.1, 32.5, 32.3
(peaks overlap), 31.5, 30.1 (peaks overlap), 29.8, 28.41, 28.35, 28.3,
3
31
(
t, J = 8.1 Hz, 2 H), 4.75 (t, J = 8.2 Hz, 1 H), 2.48 (d, JPH = 12.9 Hz, 23.1 (peaks overlap), 14.5 (peaks overlap) ppm. P NMR (162 MHz,
6
H), 2.43–2.36 (m, 8 H), 1.55–1.34 (m, 72 H), 0.96–0.93 (m, 12 CDCl ): δ = 110.6 ppm. IR (neat): ν˜ = 2921, 2851, 1578, 1481, 1399,
3
1
–
1
H) ppm. H NMR (400 MHz, [D ]toluene): δ = 8.54 (s, 2 H), 7.94–7.90
1331, 1267, 1158, 1016, 894, 757 cm . MS (MALDI-TOF): m/z = 1544
8
+
(
(
m, 4 H), 7.74–7.71 (m, 2 H), 7.69–7.68 (m, 2 H), 7.63 (s, 2 H), 7.62
s, 2 H), 7.27 (dd, J = 6.4, 3.6 Hz, 2 H), 7.13 (dd, J = 6.4, 3.6 Hz, 4 H),
[M + H] . HRMS (MALDI-TOF): calcd. for C H N O P 1543.8849 [M
9
7 120 6 9
+
+ H] ; found 1543.8735. C H N O P (1544.02): calcd. C 75.46, H
97 119 6 9
6
2
0
.09 (t, J = 8.1 Hz, 1 H), 6.02 (t, J = 8.0 Hz, 2 H), 4.76–4.73 (m, 1 H),
7.77, N 5.44; found C 75.56, H 7.46, N 5.36.
3
.55 (d, J = 12.9 Hz, 6 H), 2.43–2.36 (m, 8 H), 1.45–1.31 (m, 72 H),
PH
Au Complex 5: (see Scheme 3, b): Under an N atmosphere, to a
solution of 4a (118 mg, 0.078 mmol) in anhydrous toluene (1.5 mL)
at ambient temperature was added AuCl·S(CH3)2 (28 mg,
2
1
3
.96–0.92 (m, 12 H) ppm. C NMR (100 MHz, CD Cl ): δ = 153.2 (d,
2
2
JCP = 2.5 Hz), 153.1, 153.0, 152.8, 152.6, 152.3, 146.2 (d, JCP = 4.1 Hz),
1
3
1
3
40.4, 140.0, 139.9, 137.0 (d, JCP = 2.1 Hz), 136.53, 136.49 (d, JCP =
0
.094 mmol). After stirring for 30 min, 4a was consumed (TLC moni-
toring). The reaction mixture was concentrated in vacuo to give
61 mg of crude product as a white solid compound. Purification by
short-plug column chromatography (hexane/EtOAc = 4:1) yielded
.1 Hz), 135.8, 129.9, 129.8, 129.5, 129.3, 128.2, 127.7, 124.4, 123.2,
18.8, 118.4 (d, JCP = 4.1 Hz), 36.9 (d, JCP = 11.5 Hz), 36.1, 34.8, 34.6,
3.2, 32.43, 32.42, 32.41, 30.5, 30.2 (peaks overlap), 30.0, 29.9 (peaks
1
overlap), 28.6, 28.4, 28.3, 23.2 (peaks overlap), 14.4 (peaks over-
1
137 mg of 5 in 99 % as a white solid. H NMR (400 MHz, CDCl ):
3
lap) ppm. 31P NMR (162 MHz, CD Cl ): δ = 115.1 ppm. P NMR
31
2
2
δ = 8.17 (s, 2 H), 7.85 (dd, J = 8.0, 1.5 Hz, 2 H), 7.79–7.76 (m, 4 H),
.54–7.44 (m, 8 H), 7.29 (s, 2 H), 7.25 (s, 2 H), 5.77 (t, J = 8.3 Hz, 1
(162 MHz, [D ]toluene): δ = 113.0 ppm. MS (MALDI-TOF): m/z = 1753
8
7
+
[
7
1
M – Cl] . IR (neat): ν˜ = 2921, 2851, 1480, 1399, 1330, 1268, 1146,
3
H), 5.72 (t, J = 8.1 Hz, 2 H), 4.52 (t, J = 8.0 Hz, 1 H), 4.13 (d, J
=
PH
–1
56 cm . HRMS (MALDI-TOF): calcd. for C H AuClN O PNa
98 122 7 8
1
1
7
2
6
1
1
3.6 Hz, 3 H), 2.33–2.18 (m, 8 H), 1.45–1.28 (m, 72 H), 0.91–0.87 (m,
+
810.8339 [M + Na] ; found 1810.8268.
1
2 H) ppm. H NMR (400 MHz, [D ]toluene): δ = 8.58 (s, 2 H), 7.93–
8
.88 (m, 4 H), 7.76–7.74 (m, 2 H), 7.66 (s, 2 H), 7.60 (s, 2 H), 7.57 (s,
H), 7.27–7.25 (m, 2 H), 7.13–7.11 (m, 4 H), 6.06 (t, J = 8.0 Hz, 1 H),
.02 (t, J = 7.7 Hz, 2 H), 4.64 (t, J = 7.7 Hz, 1 H), 3.34 (d, JPH
Phosphite 4a and 4b: (see Scheme 3, a) Under an N atmosphere,
2
a flask charged with 1 (1.0 g, 0.67 mmol) and dry toluene (13 mL)
was dipped into a pre-heated oil bath (135 °C). To the mixture were
added iPr EtN (0.71 mL, 4.1 mmol) and P(OCH ) (0.48 mL,
3
=
4.4 Hz, 3 H), 2.40–2.33 (m, 8 H), 1.43–1.31 (m, 72 H), 0.94–0.91 (m,
2
3 3
2 H) ppm. 13C NMR (100 MHz, CDCl ): δ = 153.2 (two peaks over-
3
4
.1 mmol). After stirring for 16 h, the reaction mixture was cooled
lap), 152.9, 152.8, 152.5, 152.3, 143.9, 140.3, 140.2, 140.1, 138.2,
to room temperature, and concentrated in vacuo to give 1.07 g of
crude products. Purification by column chromatography (hexane/
EtOAc/CH Cl = 18:1:1) yielded 589 mg of white solids 4a in 57 %
1
1
36.7, 136.0, 135.5, 129.9, 129.8, 129.5, 128.8, 128.1, 127.7, 124.0,
22.9, 119.3, 118.0 (d, JCP = 4.1 Hz), 55.1, 36.0, 34.4, 33.0, 32.9, 32.3
2
2
1
(peaks overlap), 30.8, 30.1 (peaks overlap), 29.8 (peaks overlap),
yield and 220 mg of white solids 4b in 21 % yield. For 4a. H NMR
3
1
2
8.4, 28.3, 28.2, 23.1 (peaks overlap), 14.5 (peaks overlap) ppm.
P
(400 MHz, CDCl ): δ = 8.31 (s, 2 H), 7.98 (d, J = 8.3 Hz, 2 H), 7.75
3
31
NMR (162 MHz, CDCl ): δ = 108.5 ppm. P NMR (162 MHz, [D ]tolu-
3
8
(dd, J = 6.2, 3.4 Hz, 2 H), 7.73 (d, J = 8.3 Hz, 2 H), 7.58 (dd, J = 8.3,
ene): δ = 111.0 ppm. IR (neat): ν˜ = 2921, 2851, 1480, 1398, 1329,
8
2
8
.3 Hz, 2 H), 7.48 (dd, J = 8.3, 8.3 Hz, 2 H), 7.43 (dd, J = 6.2, 3.4 Hz,
–
1
+
1
155 cm . MS (MALDI-TOF): m/z = 1740 [M – Cl] . HRMS (MALDI-
H), 7.29 (s, 2 H), 7.21 (s, 4 H), 5.70 (t, J = 8.1 Hz, 1 H), 5.70 (t, J =
+
3
TOF): calcd. for C97
797.7964.
Phophonite 6: (see Scheme 4) Under an N2 atmosphere, a flask
H119AuClN O PNa 1797.8022 [M + Na] ; found
6 9
.1 Hz, 2 H), 4.52 (t, J = 7.2 Hz, 1 H), 3.92 (d, JPH = 8.3 Hz, 3 H),
1
2
.27–2.19 (m, 8 H), 1.42–1.28 (m, 72 H), 0.90–0.87 (m, 12 H) ppm.
1
H NMR (400 MHz, [D ]toluene): δ = 8.67 (s, 2 H), 7.81–7.78 (m, 2
8
H), 7.72–7.70 (m, 2 H), 7.67 (s, 2 H), 7.64 (s, 4 H), 7.40–7.38 (m, 2 H), charged with 1 (1.0 g, 0.67 mmol) and dry toluene (13 mL) was
7
.20–7.17 (m, 2 H), 7.08–6.96 (m, 4 H), 6.11 (t, J = 8.0 Hz, 1 H), 6.04
dipped into a pre-heated oil bath (80 °C). To the mixture was added
3
(t, J = 8.1 Hz, 2 H), 4.90 (t, J = 7.8 Hz, 1 H), 3.65 (d, JPH = 7.8 Hz, 3
PhP(NEt ) (0.21 mL, 0.81 mmol). After stirring for 20 h, the reaction
2 2
H), 2.42–2.40 (m, 8 H), 1.47–1.30 (m, 72 H), 0.96–0.93 (m, 12 H) ppm.
mixture was cooled to room temperature, and concentrated in
vacuo to give 1.21 g of crude products. Purification by column chro-
13
C NMR (100 MHz, CDCl ): δ = 153.2 (two peaks overlap), 153.0,
3
1
1
52.9, 152.8, 152.7 (d, JCP = 0.95 Hz), 147.2 (d, JCP = 5.2 Hz), 140.11, matography (hexane) and precipitation (CH Cl /CH OH = 1:8)
2 2 3
1
40.09 (two peaks overlap), 137.4 (d, JCP = 2.2 Hz), 136.4, 136.3,
818
yielded 640 mg of white solids 6 in 60 %. H NMR (400 MHz, CDCl ):
3
Eur. J. Org. Chem. 2016, 813–820
www.eurjoc.org
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
δ = 8.34 (s, 2 H), 8.02 (d, J = 8.4 Hz, 2 H), 7.85–7.81 (m, 2 H), 7.74– Supporting Information (see footnote on the first page of this
1
13
7
.72 (m, 4 H), 7.60 (dd, J = 7.0, 7.0 Hz, 2 H), 7.57–7.56 (m, 3 H), 7.48
article): The H NMR and C NMR spectra of all new compounds.
(dd, J = 7.0, 7.0 Hz, 2 H), 7.40 (dd, J = 6.2, 3.4 Hz, 2 H), 7.31 (s, 2 H),
7
1
.27 (s, 2 H), 7.25 (s, 2 H), 5.73 (t, J = 7.9 Hz, 2 H), 5.71 (t, J = 7.4 Hz,
Acknowledgments
H), 4.60 (t, J = 7.6 Hz, 1 H), 2.32–2.20 (m, 8 H), 1.47–1.27 (m, 72
1
H), 0.91–0.87 (m, 12 H) ppm. H NMR (400 MHz, [D ]toluene): δ =
8
The authors thank the Japan Society of the Promotion of Sci-
ence for an Invitational Fellowship (L-15528, long-term support
to M. P. S.). Dr. Toshiyuki Iwai, Dr. Takatoshi Ito, and Dr. Seiji
Watase at OMTRI are gratefully thanked for assistance with
HRMS and crystallographic analyses.
8
(
.70 (s, 2 H), 7.83 (dd, J = 6.4, 3.5 Hz, 2 H), 7.75–7.63 (m, 9 H), 7.46
d, J = 7.7 Hz, 2 H), 7.20 (dd, J = 6.4, 3.5 Hz, 2 H), 7.10–7.09 (m, 6
H), 7.01–6.97 (m, 2 H), 6.13–6.06 (m, 3 H), 5.01 (t, J = 7.7 Hz, 1 H),
2
.44–2.38 (m, 8 H), 1.48–1.32 (m, 72 H), 0.96–0.92 (m, 12 H) ppm.
13
C NMR (100 MHz, CDCl ): δ = 153.30, 153.25, 153.1, 152.9, 152.8,
3
1
52.6, 152.4 (d, JCP = 3.8 Hz), 140.1 (two peaks overlap), 137.0 (d,
JCP = 3.1 Hz), 136.4, 136.3, 135.4, 131.7, 130.0, 129.8, 129.6, 129.3 Keywords: Synthetic methods · Homogeneous catalysis ·
(
5
d, JCP = 3.3 Hz), 129.1, 128.9 (d, JCP = 6.2 Hz), 128.6, 128.3 (d, JCP
=
.2 Hz), 128.1, 125.6, 123.6, 123.3, 119.4 (d, JCP = 5.2 Hz), 117.1 (d,
Supramolecular chemistry · Cavitands · Introverted functionality
JCP = 1.4 Hz), 36.2, 34.5, 34.4, 33.2, 32.3 (peaks overlap), 30.1 (peaks
[
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lap) ppm. 3 P NMR (162 MHz, CDCl ): δ = 166.7 ppm. P NMR
1
31
3
(
1
162 MHz, [D ]toluene): δ = 166.0 ppm. IR (neat): ν˜ = 2921, 2850,
8
–
1
572, 1480, 1400, 1331, 1268, 1158, 893, 758 cm . MS (MALDI-TOF):
+
m/z = 1590 [M + H] . HRMS (MALDI-TOF): calcd. for C102H122N O P
1
6
8
[
+
589.9056 [M + H] ; found 1589.8893. C 02H N O P (1590.09):
1 121 6 8
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Au Complex 7: (see Scheme 4) Under an N atmosphere, to a solu-
2
tion of 6 (195 mg, 0.12 mmol) in anhydrous toluene (3 mL) at ambi-
ent temperature was added AuCl·S(CH ) (43 mg, 0.15 mmol). After
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3
2
2
stirring for 30 min, 6 was consumed (TLC monitoring). The reaction
mixture was concentrated in vacuo to give 234 mg of crude white
solid compounds. Purification by short-plug column chromatogra-
phy (hexane/EtOAc/CH Cl = 8:1:1) yielded 197 mg of 7 in 88 % as
[
5
D. J. Cram, J. Am. Chem. Soc. 1991, 113, 5707–5714; c) D. J. Cram, J. M.
Cram, Container Molecules and Their Guests, Royal Society of Chemistry,
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2
2
1
a white solid. H NMR (400 MHz, CDCl ): δ = 8.19 (s, 2 H), 8.15 (dd,
3
J = 7.2, 7.2 Hz, 2 H), 7.86 (d, J = 7.8 Hz, 2 H), 7.81–7.77 (m, 4 H),
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7
7
.73 (dd, J = 7.2, 7.2 Hz, 1 H), 7.67 (dd, J = 7.8, 3.4 Hz, 2 H), 7.53–
.45 (m, 8 H), 7.33 (s, 2 H), 7.29 (s, 2 H), 5.79 (t, J = 8.2 Hz, 1 H), 5.73
1
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(
1
t, J = 8.0 Hz, 2 H), 4.68 (t, J = 8.2 Hz, 1 H), 2.33–2.24 (m, 8 H),
.45–1.28 (m, 72 H), 0.90–0.87 (m, 12 H) ppm. H NMR (400 MHz,
1
[
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Angew. Chem. 2000, 112, 3419–3421.
[
(
D ]toluene): δ = 8.61 (s, 2 H), 7.98 (dd, J = 6.8, 3.5 Hz, 2 H), 7.91
dd, J = 6.3, 3.4 Hz, 2 H), 7.81–7.77 (m, 4 H), 7.76 (s, 2 H), 7.66 (s, 2
8
[
H), 7.62 (s, 2 H), 7.27 (dd, J = 6.3, 3.4 Hz, 2 H), 7.15–7.05 (m, 7 H),
6
1
.10–6.04 (m, 3 H), 4.80 (t, J = 7.8 Hz, 1 H), 2.43–2.38 (m, 8 H), 1.45–
.29 (m, 72 H), 1.00–0.91 (m, 12 H) ppm. C NMR (100 MHz, CDCl3):
[8] a) B. W. Purse, P. Ballester, J. Rebek Jr., J. Am. Chem. Soc. 2003, 125,
14682–14683; b) J. Rebek Jr., J. Org. Chem. 2004, 69, 2651–2660; c) T.
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1
3
δ = 153.2 (d, JCP = 2.2 Hz), 153.1, 153.0, 152.8, 152.5, 152.3, 140.3,
1
1
[
9] a) Y. Inokuma, S. Yoshioka, M. Fujita, Angew. Chem. Int. Ed. 2010, 49,
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(
(
(
(
d, JCP = 5.5 Hz), 129.4, 128.9, 128.1, 127.7, 124.0, 122.8, 119.2, 117.6
d, JCP = 4.3 Hz), 36.1, 34.4, 33.0, 32.3 (peaks overlap), 30.9, 30.1
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3
1
peaks overlap), 14.5 (peaks overlap) ppm. P NMR (162 MHz,
3
1
CDCl ): δ = 131.7 ppm. P NMR (162 MHz, [D ]toluene): δ =
1
1
3
8
33.3 ppm. IR (neat): ν˜ = 2921, 2851, 1605, 1579, 1480, 1413, 1399,
–
1
+
156, 909, 756 cm . MS (MALDI-TOF): m/z = 1844 [M + Na] . HRMS
+
(MALDI-TOF): calcd. for C102H121AuClN O PNa 1843.8230 [M + Na] ;
6 8
[
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6
511.
Tricarbonyl Compound 10: (see Table 4) This compound was iso-
lated from Conia-ene reaction of keto ester alkyne 8 under the
general reaction conditions after 16 h of heating with dichloro-
ethane as the solvent and with 30.7 mg (0.156 mmol) of substrate.
The reaction mixture was concentrated and purified by column
chromatography in 2:1 hexane/EtOAc to give 4.5 mg (14 % isolated
yield).
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1
H NMR (400 MHz, CDCl ): δ = 3.73 (s, 3 H), 3.40–3.44 (t, J = 7.6 Hz,
3
1
H), 2.40–2.44 (t, J = 7.2 Hz, 2 H), 2.22 (s, 3 H), 2.12 (s, 3 H), 1.80–
1
.87 (m, 2 H), 1.54–1.62 (m, 2 H), 1.22–1.30 (m, 2 H) ppm.
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Eur. J. Org. Chem. 2016, 813–820
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819
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
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[26] In Figure 2 (b–d) and Figure S1 (d–e), the cavitand peaks almost disap-
pear as a result of a mismatch with the NMR spectroscopic time scale.
We think there are two reasons for this. One is the slow equilibrium
between vase and kite conformers because the bulky substrate forces
the kite formation. For make sure, we tried a low-temperature NMR ex-
periment; however, we were unable to record data because of the low
solubility of its complex. The second reason is a typical pi interaction
[
20] The mechanism by which stereoselectivity occurs is not yet fully under-
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[
[
observation previously in ref.[
.
27]
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graphic data for this paper. These data can be obtained free of charge
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1
[28] Results of up- and downfield portion of the H NMR spectra are listed
in Figure S1, see Supporting Information.
P1¯, colorless, a = 13.8433(6) Å, b = 24.3818(10) Å, c = 28.6654(5) Å,
[29] The MS spectrum is contained in the Supporting Information.
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3
α = 74°, ꢀ = 88°, γ = 79°, V = 9130(7) Å , Z = 4, T = 173 K, dcalcd.
=
1
1
.302 g cm–3, μ(Mo-K
.027.
α
) = 1.723 mm , R
–1
1
= 0.0644, wR
2
= 0.1894, GOF =
[
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4
Received: November 11, 2015
Published Online: December 15, 2015
Eur. J. Org. Chem. 2016, 813–820
www.eurjoc.org
820
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim