New Insights into Aldol Reactions of Methyl Isocyanoacetate Catalyzed by Heterogenized Homogeneous Catalysts

Article abstract of DOI:10.1021/acs.nanolett.6b04827

The Hayashi-Ito aldol reaction of methyl isocyanoacetate (MI) and benzaldehydes, a classic homogeneous Au(I)-catalyzed reaction, was studied with heterogenized homogeneous catalysts. Among dendrimer encapsulated nanoparticles (NPs) of Au, Pd, Rh, or Pt lo

Full text of DOI:10.1021/acs.nanolett.6b04827

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Communication
New Insights into Aldol Reactions of Methyl Isocyanoacetate
Catalyzed by Heterogenized Homogeneous Catalysts
Rong Ye, Jie Zhao, Bing Yuan, Wen-Chi Liu, Joyce R. Araujo, Franco F. Faucher,
Matthew Chang, Christophe V. Deraedt, F. Dean Toste, and Gabor A. Somorjai
Nano Lett., Just Accepted Manuscript • DOI: 10.1021/acs.nanolett.6b04827 • Publication Date (Web): 14 Dec 2016
Downloaded from http://pubs.acs.org on December 15, 2016
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New Insights into Aldol Reactions of Methyl
Isocyanoacetate Catalyzed by Heterogenized
Homogeneous Catalysts
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‡
∥
,
⊥
†
‡
⊥
†
⊥
† §
Rong Ye†, ,
, Jie Zhao , , , Bing Yuan , , WenꢀChi Liu , ∥, Joyce Rodrigues De Araujo§
,
,
, #
‡
†
Franco F. Faucher†, Matthew Chang†, Christophe V. Deraedt†, , F. Dean Toste*, , ‡, Gabor A.
†
‡ § ∥
,
Somorjai*, , ,
†Department of Chemistry, ∥Kavli Energy NanoScience Institute, University of California,
Berkeley, California 94720, United States
‡Chemical Science Division, §Materials Science Division, Lawrence Berkeley National
Laboratory, 1 Cyclotron Road, Berkeley, California 94720, United States
ABSTRACT. The HayashiꢀIto aldol reaction of methyl isocyanoacetate (MI) and benzaldehydes,
a classic homogeneous Au(I)ꢀcatalyzed reaction, was studied with heterogenized homogeneous
catalysts. Among dendrimer encapsulated nanoparticles (NPs) of Au, Pd, Rh, or Pt loaded in
mesoporous supports and the homogeneous analogs, the Au NPs led to the highest yield and
highest diastereoselectivity of products in toluene at room temperature. The Au catalyst was
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stable, and was recycled for at least six runs without substantial deactivation. Moreover, larger
pore sizes of the support and the use of a hydrophobic solvent led to a high selectivity for the
trans diastereomer of the product. The activation energy is sensitive to neither the size of Au
NPs nor the support. A linear Hammett plot was obtained with a positive slope, suggesting an
increased electron density on the carbonyl carbon atom in the rateꢀlimiting step. IR studies
revealed a strong interaction between MI and the gold catalyst, supporting the proposed
mechanism, in which rateꢀlimiting step involves electrophilic attack of the aldehyde on the
enolate formed from the deprotonated MI.
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KEYWORDS. Heterogenized homogeneous catalyst, aldol reaction, selectivity, support effect,
mechanism, gold catalyst
Heterogeneous catalysis offers the benefit of easy separation of the catalyst from reaction
mixtures.1 For reactions reaching nearly 100% conversion, the filtration of the catalyst is the only
necessary workꢀup, besides solvent removal (if any). In addition, heterogeneous catalysts can be
applied to flow reactions,2 and easily recycled.3 These economically and ecologically beneficial
aspects of heterogeneous catalysts are in agreement with the concepts of green chemistry.
However, optimizing the product selectivity in traditional heterogeneous catalysts remains an
important challenge.4 Improvements in supported metal catalysts have predominantly focused on
engineering the metal sites.5ꢀ12 The solid support is also an important consideration in the design
of a heterogeneous catalyst.13 Strong metalꢀsupport interactions (SMSI), where the support
greatly affects the activity of active sites,14 are a good example of this phenomenon. However,
the effects of the support properties on the product selectivity have not been thoroughly
studied.15ꢀ17
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The last two decades have seen numerous advances in gold catalysis.16ꢀ23 Since the first
publication by Ito et al., the aldol reaction of methyl isocyanoacetate (MI) and aldehydes forming
2ꢀoxazolines has stood as a milestone in catalytic asymmetric synthesis.24 Later, this reaction
was widely studied with goldꢀbased25ꢀ26 and other27 homogeneous catalysts in order to explore its
synthetic scope, reaction mechanism and the effect of the ligand structure on selectivity. For
example, Togni and Pastor28 provided valuable insights into the reaction mechanism, the rateꢀ
determining step and the enantiodeterming transition states of Au(I)ꢀcomplexꢀcatalyzed aldol
reaction through NMR, kinetic isotope, and linear free energy studies. Recently, van Koten et
al.29 immobilized Pd(II) complexes with pincer ligands30 on mesoporous silica SBAꢀ15 as a
heterogenized homogeneous catalyst for the aldol reaction of MI and benzaldehyde in the
presence of a base. Even though good activity and recycling results were achieved, the trans
product selectivity was limited to 84%. Herein, we describe bridging the advantages of
heterogeneous and homogeneous catalysts using dendrimerꢀsupported heterogenized
homogeneous catalyst developed in our group.31ꢀ36 Additionally, the reaction mechanism of the
aldol reaction was investigated, providing insights into the factors that affect the product
selectivity in the heterogeneous reaction.
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Figure 1. (A) A scheme of the aldol reaction. (B) The kinetics of the aldol reaction: 1 mol%
catalyst, 22 °C in toluene. (C) Recycle tests with the same batch of Au40/G4OH/MPꢀSBAꢀ15 for
six runs: 1 mol% catalyst in chloroform, 22 °C, 2 h per run. (D) Structures of Au(I)ꢀcomplexes
used in this study. The codes originate from their corresponding CAS numbers.
Catalyst screening. NPs of Au, Pd, Rh, or Pt encapsulated in fourth generation polyamidoamine
with hydroxyl terminal groups (G4OH) were prepared, purified, and loaded into mesoporous
silica MPꢀSBAꢀ15 (MP denotes mediumꢀsized pores, vide infra), following published
protocols.37ꢀ41 The typical loading amount was 0.05 mmol of metal per gram of a supported
metal catalyst. In a typical reaction test, 0.05 mmol of 4ꢀnitrobenzaldehyde (1a), 0.075 mmol of
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MI, and 10 mg of a catalyst (containing ca. 0.5 ꢁmol of metal, determined by ICPꢀOES) were
mixed with a solvent in a reaction tube with magnetic stirring. For 18ꢀh reaction time at room
temperature using toluene as the solvent (Figure 1A), the Au40/G4OH/MPꢀSBAꢀ15 catalyzed
reaction provided the desired oxazoline in >99% yield and 97/3 of trans/cis ratio, based on 1H
NMR (see Supporting Information for details). In contrast, the use of the Pd, Rh, and Pt
counterparts as catalysts under identical conditions gave low yields and poor product selectivity
(Table 1). These observations highlight the critical role of the gold catalysts and rule out G4OH
or MPꢀSBAꢀ15 as the sole catalysts for the reaction. It is also worth noting that 1a was a
challenging substrate for the optimized homogeneous Au(I) catalyst, providing the
corresponding oxazoline in only 80% yield with a trans/cis ratio of 83/17.25 Three commercially
available Au(I) complexes (Figure 1D) were used as catalysts under the same reaction condition;
however, these catalysts showed lower activity and selectivity than the optimized Au(I) catalyst.
The yield and selectivity of the aldol reaction under similar conditions catalyzed by transition
metal ion complex catalysts of Pd, Pt, and Rh are highly dependent on the ligand structures
(Table 1).42ꢀ55 However, the Au40/G4OH/MPꢀSBAꢀ15 catalyst offers the highest activity and
selectivity, along with easy recyclability. Intrigued, we proceeded to further investigate the
reaction by heterogenized gold catalysts.
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Table 1. Comparison of yields and trans/cis selectivity for aldol reactions with selected
transition metal catalysts.
entry
1a
catalyst
yield (%)
99.9
trans/cis
97/3
ref.
Au40/G4OH/MPꢀSBAꢀ15
Pd40/G4OH/MPꢀSBAꢀ15
Pt40/G4OH/MPꢀSBAꢀ15
this work
this work
this work
2a
42.7
81/19
73/27
3a
5.1
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Rh40/G4OH/MPꢀSBAꢀ15
Au(I)ꢀ81ꢀ9
1.8
87/13
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this work
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57.4
80
68/32
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Au(I)ꢀ82ꢀ0
68/32
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Au(I)ꢀ83ꢀ1
70/30
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Au(I) complex
Pd complexes
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Rh complexes
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89/11ꢀ92/8
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aThe reactions were carried out with 0.05 mmol of 1a, 0.075 mmol of MI, 1 mol% catalyst in
toluene at 22 °C for 18 h. Yield and product selectivity were determined by 1H NMR (same
below). bBases (iꢀPr2NEt or Et3N) were used. See ref. 12 for detailed reaction conditions.
Kinetics Study. The reaction kinetics were probed, and first order kinetics was found on both
reactants (Figure 1B). When the reaction mixture was filtered after an hour, the starting materials
in the filtrate showed no change over time, suggesting that the reaction was catalyzed by
heterogeneous gold, and that no catalyst leaching into the supernatant had occurred (Figure 1B).
In fact, a blank run revealed that in the absence of a catalyst or a base, the aldol reaction did not
proceed at room temperature. Furthermore, Au3+/G4OH/MPꢀSBAꢀ15, which contained Au(III)
ions from HAuCl4, was synthesized according to a published procedure.35 Under the same
reaction condition, this Au(III) catalyst gave the product in only 3% yield, demonstrating that
Au(III) has very low activity compared to the heterogeneous Au catalysts.
Recycling test. A recycling test using the same batch of a catalyst was carried out. The product
solution was separated via centrifugation after each run, and a fresh reactant solution was mixed
with the catalyst immediately. The catalyst did not show a decrease in activity after six reaction
runs (Figure 1C), providing evidence for the stability and recyclability of the catalyst.
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Size effect study. To study the effect of size of the NPs on the catalytic reaction, Au20/G4OH,
Au40/G4OH, and Au60/G4OH were synthesized. Though the NPs described in this study are
denoted as such, they are not perfectly uniform in size: the subscript refers to the HAuCl4/G4OH
molar ratios used in the synthesis, not to the exact number of atoms in each NP. The size
distribution of these NPs was obtained from the TEM images (Figure 2). Concurrently, SPꢀSBAꢀ
15 and LPꢀSBAꢀ15 were prepared to probe the effect of the pore profile of the support.37ꢀ41 SP
and LP denote small pore and large pore, respectively. The nitrogen physisorption isotherms
(Figure 3) were obtained, and the BarrettꢀJoynerꢀHalenda (BJH) model was used to calculate the
pore size distribution. The results were summarized in Table 2.
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Figure 2. TEM images and corresponding particle size distribution statistics of Au40/G4OH (A),
(B); Au20/G4OH (C), (D); Au60/G4OH (E), (F). Scale bars are 10 nm.
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SP
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Figure 3. N2 adsorptionꢀdesorption isotherms of solid supports at 77 K with adsorption and
desorption points represented by closed and open symbols, respectively.
Table 2. Physisorption characterizations of the solid supports.a
material
SBET/m2·gꢀ1 Dpore/nm Vpore/cm3·gꢀ1
SPꢀSBAꢀ15
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8.0
0.22
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MPꢀSBAꢀ15 799
LPꢀSBAꢀ15 966
aParameters: SBET: the BET surface area. Dpore: average pore diameter calculated from the
adsorption branch of the N2 isotherm by the BJH model. Vpore: total pore volume, determined at
p/p0 = 0.984.
Au NPs with different sizes were loaded into SBAꢀ15 supports with various pore sizes,
respectively. As a result, nine supported catalysts were prepared and used to catalyze the aldol
reaction, under the same conditions as shown in Figure 1A, and the trans/cis selectivity results
have been summarized in Table 3. In general, trans selectivity was higher in catalysts with larger
pores, probably due to the lower free energy of the trans product. However, in the confined
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space of the catalysts with smaller pores, the ratio of the cis product was relatively high, likely
because of its smaller kinetic diameter. The solvent was another important factor for the trans/cis
ratio of the product. A series of solvents were tested (Table 4). In general, hydrophobic solvents
favored the trans product strongly, while hydrophilic solvents led to a relatively high ratio of the
cis product.
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Table 3. Ratios of trans/cis products from catalysts with various sizes of NPs and pore
diameters.a
support
Au20/G4OH Au40/G4OH
Au60/G4OH
79/21
SPꢀSBAꢀ15
80/20
78/22
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96/4
MPꢀSBAꢀ15 93/7
LPꢀSBAꢀ15 100/0
96/4
95/5
aAll reactions were carried out with 0.05 mmol of 1a, 0.075 mmol of MI, 1 mol% catalyst in
toluene at 22 °C for 24 h. The yield was over 90% in each case.
Table 4. Solvent effects on the aldol reaction.a
entry solvent
yield (%)
99.9
trans/cis
97/3
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7
Tolueneꢀd8
Benzeneꢀd6
CDCl3
99.9
91/9
99.9
88/12
83/17
79/21
65/35
59/41
CDCl2CDCl2
DMSOꢀd6
Acetoneꢀd6
CD3CN
96.8
99.9
99.1
99.9
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aAll reactions were carried out with 0.05 mmol of 1a, 0.075 mmol of MI, 1 mol% catalyst in the
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corresponding solvent at 22 °C for 18 h.
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Substituent effect study. A Hammett study was used to probe the rate limiting step of the
Au40/G4OH/MPꢀSBAꢀ15 catalyzed aldol reaction.28, 56 The reaction rates of benzaldehydes with
different substitution groups were compared (see Table S1). The rate data were fitted with σ, σ+,
and σ–, respectively. The σ series fit generally well, except for 8 and 9, much better than that of
σ+ or σ– (larger R2 values, plots not shown here), with the slope ρ = 0.64, as shown in Figure 4B.
The deviation of 8 and 9 might be caused by the oxygen’s interaction with electrophiles, further
lowering the reactivity of these two compounds. The slope was smaller than that obtained for the
reaction catalyzed by the homogeneous the Au(I)ꢀcomplex (ρ = 1.4), indicating that the reaction
was less sensitive to the electronic effect on the surface of the Au NP than on the Au(I)ꢀcomplex.
However, the positive slope suggested the increased electron density on the carbonyl carbon
atom in the rateꢀlimiting step, which was similar in these two types of catalysts, i.e. they
involved electrophilic attack of the aldehyde on the MI (vide infra).28
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Figure 4. (A) Structures and abbreviations of aldehydes used in this study. (B) A Hammett plot
of the reaction of substituted benzaldehydes with MI. The linear fit (blue line) did not include 8
and 9.
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Figure 5. Arrhenius plots of selected cases, focusing on (A) different catalysts, and (B) solvents
and reactants. The reaction conditions and the corresponding calculated activation energies are
given in Table 5.
Activation Energy study. The Arrhenius plots were obtained for selected cases, as shown in
Figure 5, and the calculated activation energies were listed in Table 4. For catalysts with
different sizes of Au NPs or pore profile of the support, the activation energies were very similar
(entries 1ꢀ5, Table 5). Changing the solvent from toluene to acetonitrile using the same catalyst
gave distinct trans/cis product ratio (entries 1 and 7, Table 4), however, overall reaction rates and
activation energies were very close (Figure 5B). On the contrary, benzaldehydes with various
substituents showed substantial variations in reactivity for the same catalyst. Namely, electronꢀ
donating groups increased the activation energy (Table 5).
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Table 5. Calculated activation energies of selected cases.a
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5
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7
entry catalyst
reactant Ea (kJ/mol)
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9
Au20/G4OH/MPꢀSBAꢀ15
23.2
22.4
23.3
28.6
23.9
24.2
47.5
50.1
57.4
9
1a
1a
1a
1a
1a
1ab
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Au40/G4OH/SPꢀSBAꢀ15
Au40/G4OH/MPꢀSBAꢀ15
Au40/G4OH/LPꢀSBAꢀ15
Au60/G4OH/MPꢀSBAꢀ15
Au40/G4OH/MPꢀSBAꢀ15
Au40/G4OH/MPꢀSBAꢀ15
Au40/G4OH/MPꢀSBAꢀ15
Au40/G4OH/MPꢀSBAꢀ15
7
8
aAll reactions were carried out with 0.05 mmol of aldehydes, 0.075 mmol of MI, 1 mol% catalyst
in toluene (except entry 6) at 0ꢀ35 °C for 2 h. bSolvent: CD3CN.
IR study. A series of FTꢀIR experiments was carried out to elucidate the reaction mechanism.
For the pure MI, the stretching vibration frequency of the CN group was 2163 cmꢀ1; for the C=O
group it was 1763 cmꢀ1. A fresh solution of Au60/G4OH was concentrated by rotary evaporation
to dryness, redispersed in methanol, and used in the IR study, to avoid the strong IR absorption
by SBAꢀ15. However, after addition of MI to the Au60/G4OH in methanol, the gold NPs
precipitated. The precipitate was transferred onto the IR window for study. The observed CN
stretching resonance was split into two bands, the major one at 2223 cmꢀ1, and the minor one at
2159 cmꢀ1. In addition, the C=O stretching peak shifted to 1753 cmꢀ1. These shifts could be
explained by the formation of the enolate formed via proton abstraction from the MI, where the
blue shift of the CN stretching was caused by the delocalized πꢀelectron conjugation. 2 ꢁL of MI
was added to the Au60/G4OH in methanol before a portion of the mixture was used for data
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collection, and such a procedure was repeated several times. The CN stretching peak at 2163 cmꢀ
1 grew gradually until it had a larger intensity than the 2223 cmꢀ1 peak, because the surface of the
Au NPs was gradually saturated with bound MI molecules. To the best of our knowledge, there
are few precedents27 in the literature for this phenomenon, observed by IR spectroscopy of the
cyano group stretching vibration. On the contrary, mixing 1a and Au60/G4OH in methanol did
not cause apparent peak shifts of 1a, as shown in Figure 6C. These observations supported our
proposal that the reaction mechanism on the Au surface was likely the same on the Au(I)
complex. The tertiary amine groups on the G4OH might serve as the base to accept the proton
from MI. The proposed intermediate structure is shown in Figure 6D.
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Figure 6. (A) Full FTꢀIR spectra and (B) zoomꢀin view of (a) pure MI, and (b)ꢀ(e) increasing
amount of MI in a Au60/G4OHꢀmethanol suspension. (C) Full FTꢀIR spectra of (a) G4OH/MeOH,
(b) 1a/MeOH, and (c) 1a/G4OH/MeOH. (D) The proposed intermediate structure: the
deprotonated MI forms an enolate on the gold surface, and the tertiary amines in the dendrimer
function as the Brønsted base to accept the proton from MI.
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The current work provides a firm basis for the development of efficient heterogenized
homogeneous catalysts with high stereoselectivity in aldol reactions. We established that larger
pore sizes of the support and the use of a hydrophobic solvent leads to a high selectivity for the
trans product in the conversion of aldehydes and MI to 2ꢀoxazolines. The reaction mechanism on
the Au surface was found to be analogous to the homogeneous Au(I) catalyzed transformation.
The rateꢀlimiting step involves electrophilic attack of the aldehyde on the enolate formed from
the deprotonated MI, which was supported by the Hammett study and IR study. Furthermore, the
use of a heterogenized homogenous gold catalyst at room temperature in a hydrophobic solvent
did not cause any observable leaching or catalyst deactivation. Thus, the high selectivity of our
catalyst in the studied aldol reaction adds to the benefits of simple postꢀreaction workꢀup and
catalyst recyclability, which will lead to a green version of this chemistry.
ASSOCIATED CONTENT
Supporting Information.
Supporting Information Available: Experimental Details and supplementary data (PDF). This
material is available free of charge via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
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Corresponding Author
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*fdtoste@berkeley.edu
*somorjai@berkeley.edu
Present Addresses
#Divisão de Metrologia de Materiais, Instituto Nacional de Metrologia, Qualidade e Tecnologia,
Av. Nossa Senhora das Graças, 50, 25250ꢀ020, Duque de Caxias, RJ, Brazil.
Author Contributions
⊥R. Y., J. Z., and B. Y. contributed equally.
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
We acknowledge support from the Director, Office of Science, Office of Basic Energy Sciences,
Division of Chemical Sciences, Geological and Biosciences of the US DOE under contract
DEAC02ꢀ05CH11231. We thank Profs. A. Paul Alivisatos and Peidong Yang for the use of
TEM. J.R.A. acknowledges CNPq for her fellowship 234217/2014ꢀ6. We acknowledge Dr.
Aleksandr V. Zhukhovitskiy for proofreading, and Dr. Miao Zhang for assistance on
physisorption tests.
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REFERENCES
5
6
(1) Wight, A.; Davis, M., Chem. Rev. 2002, 102, 3589ꢀ3614.
7
8
9
(2) Noël, T.; Buchwald, S. L., Chem. Soc. Rev. 2011, 40, 5010ꢀ5029.
(3) Astruc, D.; Lu, F.; Aranzaes, J. R., Angew. Chem. Int. Ed 2005, 44, 7852ꢀ7872.
(4) Ye, R.; Hurlburt, T. J.; Sabyrov, K.; Alayoglu, S.; Somorjai, G. A., Proc. Natl. Acad. Sci. U. S.
A. 2016, 113, 5159ꢀ5166.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(5) Iglesia, E.; Reyes, S. C.; Madon, R. J.; Soled, S. L., Adv. Catal. 1993, 39, 221ꢀ302.
(6) Chen, J. G., Chem. Rev. 1996, 96, 1477ꢀ1498.
(7) Bell, A. T., Science 2003, 299, 1688ꢀ1691.
(8) Zhou, K.; Wang, X.; Sun, X.; Peng, Q.; Li, Y., J. Catal. 2005, 229, 206ꢀ212.
(9) Lee, I.; Delbecq, F.; Morales, R.; Albiter, M. A.; Zaera, F., Nat. Mater. 2009, 8, 132ꢀ138.
(10) Xia, Y.; Xiong, Y.; Lim, B.; Skrabalak, S. E., Angew. Chem. Int. Ed 2009, 48, 60ꢀ103.
(11) Xin, H. L.; Alayoglu, S.; Tao, R.; Genc, A.; Wang, C.ꢀM.; Kovarik, L.; Stach, E. A.; Wang,
L.ꢀW.; Salmeron, M.; Somorjai, G. A., Nano Lett. 2014, 14, 3203ꢀ3207.
(12) Niu, Z.; Becknell, N.; Yu, Y.; Kim, D.; Chen, C.; Kornienko, N.; Somorjai, G. A.; Yang, P.,
Nat. Mater. 2016, 15, 1188ꢀ1194.
(13) Davis, M. E., Nature 2002, 417, 813ꢀ821.
(14) Tauster, S. J., Acc. Chem. Res. 1987, 20, 389ꢀ394.
(15) Jones, C. W.; Tsuji, K.; Davis, M. E., Nature 1998, 393, 52ꢀ54.
(16) Gross, E.; Liu, J. H.; Alayoglu, S.; Marcus, M. A.; Fakra, S. C.; Toste, F. D.; Somorjai, G.
A., J. Am. Chem. Soc. 2013, 135, 3881ꢀ3886.
(17) Yasukawa, T.; Miyamura, H.; Kobayashi, S., ACS Catal. 2016, 6, 7979ꢀ7988.
(18) Zhukhovitskiy, A. V.; Mavros, M. G.; Queeney, K. T.; Wu, T.; Voorhis, T. V.; Johnson, J. A.,
J. Am. Chem. Soc. 2016, 138, 8639ꢀ8652.
(19) Gorin, D. J.; Toste, F. D., Nature 2007, 446, 395ꢀ403.
(20) Min, B. K.; Friend, C. M., Chem. Rev. 2007, 107, 2709ꢀ2724.
(21) Niu, K.ꢀY.; Fang, L.; Ye, R.; Nordlund, D.; Doeff, M. M.; Lin, F.; Zheng, H., Angew. Chem.
Int. Ed. 2016, 55, 14272ꢀ14276.
(22) Corma, A.; Garcia, H., Chem. Soc. Rev. 2008, 37, 2096ꢀ2126.
(23) Della Pina, C.; Falletta, E.; Prati, L.; Rossi, M., Chem. Soc. Rev. 2008, 37, 2077ꢀ2095.
(24) Ito, Y.; Sawamura, M.; Hayashi, T., J. Am. Chem. Soc. 1986, 108, 6405ꢀ6406.
(25) Hubbert, C.; Hashmi, A. S. K., GoldꢀCatalyzed Aldol and Related Reactions. In Modern
Gold Catalyzed Synthesis, WileyꢀVCH Verlag GmbH & Co. KGaA: 2012; pp 237ꢀ261.
(26) Trost, B. M.; Brindle, C. S., Chem. Soc. Rev. 2010, 39, 1600ꢀ1632.
(27) Gulevich, A. V.; Zhdanko, A. G.; Orru, R. V. A.; Nenajdenko, V. G., Chem. Rev. 2010, 110,
5235ꢀ5331.
(28) Togni, A.; Pastor, S. D., J. Org. Chem. 1990, 55, 1649ꢀ1664.
(29) Mehendale, N. C.; Sietsma, J. R. A.; de Jong, K. P.; van Walree, C. A.; Gebbink, R. J. M. K.;
van Koten, G., Adv. Synth. Catal. 2007, 349, 2619ꢀ2630.
(30) Van der Boom, M. E.; Milstein, D., Chem. Rev. 2003, 103, 1759ꢀ1792.
(31) Coperet, C.; Chabanas, M.; SaintꢀArroman, R. P.; Basset, J. M., Angew. Chem. Int. Ed 2003,
42, 156ꢀ181.
(32) de Almeida, M. P.; Carabineiro, S. A. C., Chemcatchem 2012, 4, 18ꢀ29.
(33) Warner, M. C.; Bäckvall, J.ꢀE., Acc. Chem. Res. 2013, 46, 2545ꢀ2555.
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Page 17 of 17
Nano Letters
1
2
3
4
5
(34) Witham, C. A.; Huang, W.; Tsung, C.ꢀK.; Kuhn, J. N.; Somorjai, G. A.; Toste, F. D., Nat.
Chem. 2010, 2, 36ꢀ41.
(35) Gross, E.; Liu, J. H.ꢀC.; Toste, F. D.; Somorjai, G. A., Nat. Chem. 2012, 4, 947ꢀ952.
(36) Ye, R.; Yuan, B.; Zhao, J.; Ralston, W. T.; Wu, C.ꢀY.; Unel Barin, E.; Toste, F. D.; Somorjai,
G. A., J. Am. Chem. Soc. 2016, 138, 8533ꢀ8537.
(37) Zhao, D.; Feng, J.; Huo, Q.; Melosh, N.; Fredrickson, G. H.; Chmelka, B. F.; Stucky, G. D.,
Science 1998, 279, 548ꢀ552.
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
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31
32
33
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40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(38) Crooks, R. M.; Zhao, M., Adv. Mater. 1999, 11, 217ꢀ220.
(39) Crooks, R. M.; Zhao, M.; Sun, L.; Chechik, V.; Yeung, L. K., Acc. Chem. Res. 2001, 34,
181ꢀ190.
(40) Kim, Y. G.; Oh, S. K.; Crooks, R. M., Chem. Mater. 2004, 16, 167ꢀ172.
(41) Huang, W.; Kuhn, J. N.; Tsung, C.ꢀK.; Zhang, Y.; Habas, S. E.; Yang, P.; Somorjai, G. A.,
Nano Lett. 2008, 8, 2027ꢀ2034.
(42) Nesper, R.; Pregosin, P. S.; Püntener, K.; Wörle, M., Helv. Chim. Acta 1993, 76, 2239ꢀ2249.
(43) Rodríguez, G.; Lutz, M.; Spek, A. L.; van Koten, G., Chem. Eur. J. 2002, 8, 45ꢀ57.
(44) Gosiewska, S.; Herreras Martinez, S.; Lutz, M.; Spek, A. L.; van Koten, G.; Klein Gebbink,
R. J. M., Eur. J. Inorg. Chem. 2006, 2006, 4600ꢀ4607.
(45) Yoon, M. S.; Ramesh, R.; Kim, J.; Ryu, D.; Ahn, K. H., J. Organomet. Chem. 2006, 691,
5927ꢀ5934.
(46) Gosiewska, S.; Martinez Herreras, S.; Lutz, M.; Spek, A. L.; Havenith, R. W. A.; van Klink,
G. P. M.; van Koten, G.; Gebbink, R. J. M. K., Organometallics 2008, 27, 2549ꢀ2559.
(47) Fossey, J. S.; Richards, C. J., Organometallics 2002, 21, 5259ꢀ5264.
(48) Albrecht, M.; Kocks, B. M.; Spek, A. L.; van Koten, G., J. Organomet. Chem. 2001, 624,
271ꢀ286.
(49) Stark, M. A.; Richards, C. J., Tetrahedron Lett. 1997, 38, 5881ꢀ5884.
(50) Motoyama, Y.; Kawakami, H.; Shimozono, K.; Aoki, K.; Nishiyama, H., Organometallics
2002, 21, 3408ꢀ3416.
(51) Gorla, F.; Togni, A.; Venanzi, L. M.; Albinati, A.; Lianza, F., Organometallics 1994, 13,
1607ꢀ1616.
(52) Longmire, J. M.; Zhang, X.; Shang, M., Organometallics 1998, 17, 4374ꢀ4379.
(53) Williams, B. S.; Dani, P.; Lutz, M.; Spek, A. L.; van Koten, G., Helv. Chim. Acta 2001, 84,
3519ꢀ3530.
(54) Gagliardo, M.; Selander, N.; Mehendale, N. C.; van Koten, G.; Klein Gebbink, R. J. M.;
Szabó, K. J., Chem. Eur. J. 2008, 14, 4800ꢀ4809.
(55) Soloshonok, V. A.; Kacharov, A. D.; Avilov, D. V.; Ishikawa, K.; Nagashima, N.; Hayashi,
T., J. Org. Chem. 1997, 62, 3470ꢀ3479.
(56) Hansch, C.; Leo, A.; Taft, R. W., Chem. Rev. 1991, 91, 165ꢀ195.
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