Bulk gold-catalyzed reactions of diazoalkanes with amines and O2 to give enamines

Article abstract of DOI:10.1007/s10562-010-0339-7

Bulk gold powder, consisting of approximately 5-50 μm particles, catalyzes reactions of diazoalkanes E(H)C=N₂, where E is CO ₂Et or PhC(O), with amines R¹R²NH and O ₂ to give enamine products (R¹R²N)(E)C=CH(E) in 58-94% yield. The reactions are proposed to occur by initial formation of surface-bound (E)(H)C: carbene groups that are attacked by nucleophilic amines. The enamine products are very different than those obtained in reactions catalyzed by homogeneous transition metal complexes. These reactions of diazoalkanes, amines, and O₂ represent a new type of bulk gold-catalyzed reaction.

Full text of DOI:10.1007/s10562-010-0339-7

Catal Lett (2010) 137:8–15
DOI 10.1007/s10562-010-0339-7
Bulk Gold-Catalyzed Reactions of Diazoalkanes with Amines
and O2 to Give Enamines
•
Yibo Zhou Robert J. Angelici L. Keith Woo
•
Received: 2 February 2010 / Accepted: 19 March 2010 / Published online: 20 April 2010
Ó Springer Science+Business Media, LLC 2010
Abstract Bulk gold powder, consisting of approximately
5–50 lm particles, catalyzes reactions of diazoalkanes
E(H)C=N2, where E is CO2Et or PhC(O), with amines
R1R2NH and O2 to give enamine products (R1R2N)
(E)C=CH(E) in 58–94% yield. The reactions are proposed
to occur by initial formation of surface-bound (E)(H)C:
carbene groups that are attacked by nucleophilic amines.
The enamine products are very different than those
obtained in reactions catalyzed by homogeneous transition
metal complexes. These reactions of diazoalkanes, amines,
and O2 represent a new type of bulk gold-catalyzed
reaction.
hydrocarbon and alcohol oxidation [1–8]. On the other
hand, bulk gold metal is well-known for its poor catalytic
properties [1]. However, we have shown in previous
studies that bulk gold powder with particle sizes of
*1,000 nm is capable of catalyzing reactions of isocya-
nides (C:N–R) with amines and O2 to produce carbodii-
mides (in the case of primary amines) [9] or ureas (in the
case of secondary amines) [10], and reactions of carbon
monoxide CO with primary amines and O2 to give ureas
[11]. Bulk gold powder also catalyzes the oxidation (O2) of
CO to CO2 under alkaline conditions [12]. We have also
shown that primary and secondary amines with O2 give
imines (Eq. 1) using gold powder [13] and Au/Al2O3 (with
C50 nm Au particles) [14]
Keywords Gold ꢀ Catalysis ꢀ Amines ꢀ Enamines ꢀ
Oxidation
R1
Au
R1
(1)
+ ½ O2
R2
+ "H2O"
N
N
R2
H
1 Introduction
as catalysts. Recently, others have shown that these
oxidative dehydrogenation reactions of amines are cat-
alyzed by the nanogold catalysts Au/TiO2, Au/C and
Au/CeO2 [15–17]. Many of our studies of bulk gold-
catalyzed reactions were inspired by known reactivities
of ligands (e.g., CO and C:N–R) in transition metal
complexes [18]. In one recent investigation, we used
known reactions of diazoalkanes (R2C=N2) [19–24]
with transition metal complexes that give carbene
complexes (M = CR2) to generate carbene groups
(:CR2) on gold powder surfaces. Chemical evidence for
these carbenes was the observation that gold powder
catalyzes the coupling of two carbene groups in the
reaction: 2 R2C=N2 ? R2C=CR2 ? 2 N2 [25]. For the
specific case of ethyl diazoacetate (EDA), the reaction
(Eq. 2) gives both cis and trans olefinic products. A
variety of
Nano-sized gold particles (\5 nm) supported on metal
oxides catalyze a variety of reactions including CO,
Electronic supplementary material The online version of this
article (doi:10.1007/s10562-010-0339-7) contains supplementary
material, which is available to authorized users.
Y. Zhou ꢀ R. J. Angelici (&) ꢀ L. Keith Woo
Ames Laboratory and Department of Chemistry, Iowa State
University, Ames, IA 50011-3111, USA
e-mail: angelici@iastate.edu
Y. Zhou
e-mail: yibozhou@iastate.edu
L. Keith Woo
e-mail: kwoo@iastate.edu
123

Bulk Gold Catalysis
9
CO2Et
CO2Et
EtO2CCH=N2
-N2
EtO2C
CO2Et
Au
EtO2CCH=N2
-N2
(2)
+
EtO2C
Au
EDA
v homogeneous complexes are also known to catalyze
the conversion of diazoalkanes into olefins [19–24, 26–
30]. In another type of carbene reactivity, gold powder
catalyzes reactions of diazoalkanes with styrenes to
give cyclopropanes [25]. Carbene ligands in metal
complexes are also known to be susceptible to attack
by amines (Eq. 3) [31, 32]. Such a
amines (Eq. 1). Depending on the reactants and the reac-
tion conditions, these other products are also sometimes
observed. The primary purpose of this study was to dem-
onstrate a fundamentally new type of catalytic activity for
bulk gold, which is such a poor catalyst of so many other
reactions [1].
R1
R2
R
2 Experimental Section
(3)
R
R
+ HNR1R2
N
R
C
C
H
M
M
2.1 General Methods
reaction is proposed to be a key step in the reaction of
diazoalkanes with amines to give N–H insertion products
(Eq. 4) when catalyzed by a variety of homogeneous tran-
sition metal complexes. For reviews involving catalyzed
diazo compound N–H insertion reactions, see: [33–44]. For
examples of highly enantioselective metal-catalyzed inter-
molecular carbenoid N–H insertion reactions, see: [45].
Among these catalysts is an N-heterocyclic carbene com-
plex of Au(I) [46, 47]. Also relevant to the present report is
the copper metal-catalyzed N–H insertion reaction (Eq. 5)
of a-diazoacetophenone and aniline [48].
Acetonitrile and 1,2-dichloroethane were refluxed under N2
overnight with CaH2 and distilled before use. Toluene and
THF were refluxed under N2 over sodium-benzophenone
and distilled before use. HAuCl4 was ordered from Strem
Chemicals, Inc.; ethyl diazoacetate (EDA) and all amines
were purchased from Sigma–Aldrich and used as received.
a-Diazoacetophenone [49, 50], Me-MPDA [51, 52] and
PhCH=N2 [53, 54] were prepared according to literature
procedures.
cat:
EtO2CCH=N2 + R1R2NH ꢁ! EtO2CCH2ꢁNR1R2 + N2
2.2 General Procedure for the Preparation of Gold
Powder
ð4Þ
Cu
PhCOCH=N2 + PhNH2 ꢁ! PhCOCH2NHPh + N2
The gold powder used in the catalytic studies was prepared
as described in detail previously [25]. It involved reduction
of HAuCl4 with hydroquinone. The resulting gold powder
was washed with methanol, treated with piranha solution
(H2O2/H2SO4), washed with water, and then with metha-
nol. Drying at 110 °C in air gave a dull brown Au powder.
After one reaction of EDA with an amine and O2, the gold
powder had a shiny gold appearance and a low surface area
(0.35 m2/g) [55]. It is this shiny gold powder that was used
in the catalytic reactions reported in this paper. The powder
consisted of large particles (5–50 lm), which have been
previously characterized by electron microscopy [14, 25].
After each use in a catalytic reaction, the gold powder was
cleaned by sequential washing with CH3CN, CH2Cl2, and
CH3OH. Then, it was treated with piranha solution, suc-
cessively washed with water and methanol, and dried at
110 °C in air. With each use in a catalytic reaction, its
catalytic activity decreased slightly. After ten uses, the gold
powder was completely regenerated by dissolving it in
aqua regia to form HAuCl4 which was converted to Au
powder by the procedures described above [25].
ð5Þ
In the present study, we examine gold powder catalysis
of the reactions of diazoalkanes with amines and O2. If
gold catalyzed any reaction of these reactants, we expected
it to give N–H insertion products based on the reactions in
Eqs. 4 and 5. Instead, it gives the unexpected enamine
product, as illustrated by the reaction of EDA (Eq. 6).
Because gold powder catalyzes other reactions of the
reactants, one might also
R1R2NH
EtO2C
R2R1N
EtO2C
R2R1N
CO2Et
Au, O2, –H2O, –N2
+
+
CH3CN, 60 °C
24 h
2 EtO2CCHN2
CO2Et
EDA
1-8
(Z)
1-8
(E)
n-BuNH (5),
(3), (i-Pr)2N (4),
N
R1R2N =
1
2
( ),
( ), O
N
N
6
PhCH2NH ( ),
NH
7
(
8
)
), t-BuNH (
(6)
expect olefinic products from the coupling of EDA (Eq. 2)
and imines from the oxidative dehydrogenation of the
123

10
Y. Zhou et al.
2.3 General Procedure for Gold Catalysis
Table 1 Gold powder catalyzed reactions of EDA with piperidine
and O2 according to Eq. 7
A glass tube (2.5 9 18 cm, 85 mL volume) was charged
with gold powder (1.0 g), and then a solution of the amine
(0.6 mmol) and ethyl diazoacetate (0.2 mmol) in the
desired solvent (5 mL) was added. Oxygen gas was intro-
duced by a balloon filled with *1 L (*40 mmol) of O2,
which was attached to a syringe needle that was inserted
into the septum covering the opening of the tube. The
mixture was heated to 60 °C and stirred vigorously with a
magnetic stirbar for 24 h. The mixture was allowed to cool
to room temperature, and the solution was decanted. Ace-
tonitrile (3 9 5 mL) was used to wash the gold, and the
solvent was removed under reduced pressure from the
combined solution and washings. Triphenylmethane
(0.1 mmol) was added to the crude product as an internal
Entry
Solvent
(E)-1a
1
CH3CN
CH3CN
CH3CN
Toluene
Toluene
THF
94%
6%
2b
3c
4
N.R.
82%d
38%e
17%g
3%
5
6f
7
MeOH
8
ClCH2CH2Cl
0
0.2 mmol of EDA and 0.6 mmol of piperidine in 5 mL of solvent
with 1.00 g of Au powder under *1.0 atm O2 for 24 h at 60 °C
a
Yields were determined by 1H NMR with Ph3CH as the internal
standard
b
1
Under *1.0 atm Ar
standard for H NMR determination of the yield and E/Z
c
No Au catalyst
ratios. Enamine products were identified by comparison of
their 1H NMR spectra with those of authentic samples.
These samples were prepared [56–59] as described in the
Electronic Supplementary Material where 1H and 13C
NMR and mass spectral data for all of the products are also
given.
d
Imine byproduct 1b was observed (E)-1:1b = 1:1
e
At 80 °C, (E)-1:1b = 1:2
For 45 h
f
g
(E)-1:1b = 1.0:0.55
entry 3). We also examined the reaction of EDA with
piperidine in other solvents at 60 °C (Table 1, entries 4–8).
No products resulting from N–H insertion or dimerization
of EDA were observed in any of the solvents, and enamine
(E)-1 was formed as the major product except in
ClCH2CH2Cl where no enamine 1 or imine 1b was
detected, as piperidine reacted quantitatively with
ClCH2CH2Cl to afford N-(2-chloroethyl)piperidine and
piperidine hydrochloride (entry 8). In toluene at 60 °C, an
82% yield of (E)-1 was obtained (Table 1, entry 4), but at
80 °C (entry 5) a significant amount of the imine 1b ((E)-
1:1b = 1:1), which would be produced in the gold powder-
catalyzed oxidative dehydrogenation of piperidine (Eq. 8)
[13, 14], was also observed. Only 17% of (E)-1 was
3 Results and Discussion
3.1 Reaction of Ethyl Diazoacetate (EDA) with
Piperidine and O2
Initial studies of the reactions of diazoalkanes with amines
and O2 were performed with 0.60 mmol of piperidine and
0.20 mmol of EDA in 5 mL of CH3CN at 60 °C using
1.00 g of shiny gold powder under 1.0 atm of O2. The
reaction generates exclusively enamine (E)-1 in 94% yield
after 24 h at 60 °C (Eq. 7). Products resulting from N–H
insertion or
H
N
N
Au, O2
EtO2C
N
CO2Et
H
Au, O2
2
N
(8)
+ "2 H2O"
2 EtO2CCHN2
+
+ "H2O"
(7)
CH3CN
or toluene
CH3CN, 60 °C
94% yield
N
1b
H
(E)-1
obtained in THF solvent, the byproduct 1b also being
observed ((E)-1:1b = 1:0.55) (entry 6). Methanol gave 3%
of (E)-1 (entry 7) as the only product. Therefore, acetoni-
trile was found to be the optimal solvent for this transfor-
mation and was used in all subsequent studies.
dimerization of EDA were not detected. Oxygen is clearly
a reactant because the reaction of EDA with piperidine
occurs to only a small extent, and no other products are
formed when the reaction is run under an argon atmosphere
(Table 1, entry 2). The low 6% yield of (E)-1 that occurs
under Ar is presumably due to the presence of adventitious
O2. The gold powder is essential because no reaction
occurs when EDA, piperidine, and O2 are combined at
60 °C in acetonitrile in the absence of the gold (Table 1,
To gain a more detailed understanding of the reaction,
the rate of reaction (Eq. 7) was measured at several
piperidine concentrations. As shown in Fig. 1, the rates
increased significantly with increasing concentration of
amine. The dependence of the rates on amine concentration
123

Bulk Gold Catalysis
11
100
90
80
70
60
50
40
30
20
10
Table 2 Gold powder-catalyzed reactions of EDA with amines and
O2 according to Eq. 6
Entry
1
Amine
Product
Yielda
94%
E/Zb
1
E
20 mM piperidine
120 mM piperidine
240 mM piperidine
480 mM piperidine
0
0
4
8
12
16
20
24
2
3
2
3
82%
79%
E
Time, hour
Fig. 1 Formation of enamine as a function of time in the reaction
(Eq. 7) of EDA (40 mM) with piperidine in acetonitrile at 60 °C
under 1.0 atm of O2 as catalyzed by 1.0 g of gold powder
Ec
is similar to that observed in gold powder-catalyzed reac-
tions of secondary amines with isocyanides [10]. This
amine dependence suggests that the rates will also depend
on the nature of the amine involved in the reaction, as
discussed below.
4
5
6
7
iPr2NH
nBuNH2
4
5
6
7
58%
89%
78%
86%
5:1d
Z
1:3e
We were concerned that soluble gold species, such as
stabilized nanoparticles or Au(I) and/or Au(III) com-
plexes, may be the active form of the catalyst. In order to
test for this possibility, we ran the reaction (Eq. 7) of
EDA (0.20 mmol) and piperidine (0.60 mmol) in CH3CN
(5 mL) under 1.0 atm of O2 in the presence of 1.0 g of
gold powder at 60 °C. The gold was in a very active form
as it had been used in only two previous reactions after
being prepared from HAuCl4 (see ‘‘Experimental Sec-
tion’’). Triphenylmethane (0.0447 mmol) was added as a
GC standard. After 2.5 h of reaction, the yield of the
enamine product (E)-1 was 44%. At that time, 2.5 mL of
the reaction solution at 60 °C was removed by syringe
and added to an empty tube, which did not contain gold
powder. After adding an O2 atmosphere, the tube was
heated to 60 °C for an additional 23 h. GC analysis of the
solution showed that no additional (E)-1 was formed, and
the amount of unreacted EDA was the same as that
observed after being separated from the gold powder.
These results showed that no catalytically-active species
were present in the solution. Heating at 60 °C of the other
2.5 mL of the original solution, which still contained the
gold powder (1.0 g), was continued under an O2 atmo-
sphere. After 5.5 h, the yield of (E)-1 was 97%. These
experiments demonstrate that solid gold, and not a solu-
tion-soluble species, is the actual catalyst of the reaction.
Similar experiments showed that solid gold powder was
the actual catalyst of the reaction of CO, O2, and primary
amines to give ureas [11], the oxidative-dehydrogenation
of amines to give imines [13, 14], and the reaction of
carbene precursors (diazoalkanes and 3,3-diphenylcyclo-
propene) to give olefins [25].
PhCH2NH2
1:12
8
9
tBuNH2
8
9
85%
90%
1:8
NH2CH2CH2NH2
Z
10
11
PhNH2
N.R.f
N.R.f
p-Me2NC6H4NH2
0.2 mmol of EDA and 0.6 mmol of amine in 5 mL of CH3CN with
1.00 g of Au powder at 60 °C under O2 (*1 atm) for 24 h
a
Yields were determined by 1H NMR with Ph3CH as the internal
standard
b
1
(E,Z) isomers were determined by H NMR, NOE and comparison
of the data with authentic samples. (E/Z) ratio is the ratio of the
1
olefinic protons of the (E)- and (Z)-isomers in H NMR spectra
N
c
Imine 3b
: (E)-3 = 0.1:1
N
d
e
f
Imine 4b (CH3)2C=NCH(CH3)2:(E)-4 = 0.2:1
Imine 6b PhCH=NCH2Ph:(Z)-6 = 0.25:1
No reaction
3.2 Reactions of Other Diazoalkanes and Amines
Reactions (Eq. 6) of EDA with aliphatic secondary amines
(entries 1–4) and primary amines (entries 5–9) in CH3CN
at 60 °C under oxygen using gold powder as the catalyst
123

12
Y. Zhou et al.
(Table 2) provided the corresponding enamines in good to
high yields. The cyclic secondary amines, piperidine (entry
1), morpholine (entry 2), and pyrrolidine (entry 3), and
primary amines, n-BuNH2 (entry 5), cyclohexylamine
(entry 7), t-BuNH2 (entry 8) and NH2CH2CH2NH2 (entry
9), produced enamines in 78–94% yield. The lower yields
from pyrrolidine (entry 3), diisopropylamine (entry 4), and
benzylamine (entry 6) are due to the competing formation
of imines resulting from the gold catalyzed oxidative-
dehydrogenation of these amines (Eqs. 1 and 8) [13, 14].
formation of a hydrogen bond between the free NH and the
carbonyl oxygen as shown in Scheme 1, which was pro-
posed by Iwanami as the reason for the formation of (Z)-
enamines from the reactions of DMAD with primary
amines [61]. In products obtained from primary amines, the
(Z)-enamines show a broad singlet for the NH proton at
1
low field ([8.0 ppm) in the H NMR spectrum due to the
formation of a hydrogen bond, but the (E)-isomers show
the NH proton at around 4.7 ppm.
O
2 EtO2CCH=N2
+
NH2CH2CH2NH2 CH3CN, 60 °C
EtO2C
NH
HN
Au, O2, –H2O
CO2Et
(9)
NH
CO2Et
H2N
9
(Z)-
10
(Z)-
90% yield
Authentic samples of enamines 1–8 were prepared in
essentially quantitative yields from reactions of diethyl
acetylenedicarboxylate (DEAD) with amines (Eq. 10) (see
Electronic Supplementary Material). The configurations of
the (E)- and (Z)-isomers were established by comparison of
No reaction occurred between aniline or p-Me2NC6H4NH2
and EDA (entries 10 and 11), even in the presence of added
DABCO or Et3N base.
Of particular interest are the relative amounts of the E
and Z isomers produced from the different amines. Sec-
ondary amines give primarily E-isomers (entries 1–4),
while primary amines favor Z-isomers (entries 5–9). The
cyclic secondary amines produced exclusively E-isomers
(entries 1–3), while primary amines n-BuNH2 and
NH2CH2CH2NH2 yielded only Z-isomers (entries 5 and 9).
1
their H NMR spectral data with those of the dimethyl
analogs reported by Vernon [58, 59], Dolfini [62], and
Saidi [63]. The (E)-enamines show a singlet near 4.7 ppm
for the olefinic proton, while the (Z)-isomers show a singlet
at about 5.1 ppm.
EtO2C
R2R1N
CO2Et
H
EtO2C
CO2Et
EtO2C
R2R1N
H
+
+
EtOH, 0 °C-r.t.
R1R2NH
CO2Et
(10)
1-8
(E)
1-8
(Z)
n-BuNH (5), PhCH NH (6),
(3), (i-Pr)2N (4),
N
R1R2N =
1
2
N ( ),
2
( ), O
N
NH
7
8
( ), t-BuNH ( )
In contrast, diisopropyl amine (entry 4, E/Z = 5:1), ben-
zylamine (entry 6, E/Z = 1:3), and t-BuNH2 (entry 8, E/
Z = 1:8) were less stereoselective. In the case of the pri-
mary diamine NH2CH2CH2NH2 (entry 9), the formation of
product (Z)-9 presumably resulted from the stereoselective
generation of enamine (Z)-10, which cyclized to (Z)-9
(Eq. 9). The 1H NMR spectrum of (Z)-9 is the same as that
reported in the literature [60] for this compound. The (E)-
selectivity for the reaction of EDA with secondary amines
is very similar to the reactions of dimethyl acetylenedi-
carboxylate (DMAD) with amines in which the (E)-con-
figuration of the enamine esters was shown to be
thermodynamically preferred [56–59]. The dominant (Z)-
selectivity for primary amines is presumably due to the
The reactions of a-diazoacetophenone PhCOCH=N2
with amines have been reported to yield N–H insertion
products using Cu metal powder as the catalyst (Eq. 5)
[48]. We also investigated these reactions with the gold
powder catalyst. However, no N–H insertion occurred
EtO2C
NH
EtO2C
N
CO2Et
H
H
OEt
Ph
Ph
H
O
4.74 ppm
6
(E)-
8.40 ppm (Z)-6
Scheme 1 Effect of hydrogen bonding in the (Z)-isomer on the NH
chemical shift
123

Bulk Gold Catalysis
13
under conditions used in our gold metal catalyzed reac-
tions. The reaction of PhCOCH=N2 with piperidine pro-
vided only enamine (E)-11 in 90% yield after heating 29 h
in CH3CN at 60 °C (Eq. 11); with the primary amine n-
BuNH2, only the enamine (Z)-12 was obtained in 85%
yield under the same conditions (Eq. 12). As in the reac-
tions of EDA, the E isomer was obtained with the sec-
ondary amine, and the Z-isomer was the only product with
the primary amine. Heating a mixture of PhCOCH=N2 and
aniline under the same conditions gave no N–H insertion
product or enamine; however, it gave a 30% yield of the
olefin product 13 (cis/trans = 1:3) resulting from the gold
catalyzed dimerization of PhCOCH=N2 and oxazole
product 14 (35% yield) resulting from the reaction of the
carbene intermediate with the MeCN solvent (Eq. 13), as
reported previously [25].
reported to be catalyzed by complexes of Ru, Fe, and Cu
[33–45], we are not aware of a previous report of the un-
catalyzed reaction.
MeO2C
MeO2C
H
H
N
Au or without Au, O2
N
N2
+
CH3CN, 60 °C
24 h
(14)
Me
Me
15
Me-MPDA
3.3 Mechanistic Considerations for the Gold-Catalyzed
Reactions of Diazoalkanes with Amines and O2
(Eq. 6)
On the basis of previous studies of gold powder-catalyzed
reactions (see ‘‘Introduction’’), there are three logical
mechanisms (Scheme 2) for the formation of enamine (E)-
1 from EDA and piperidine. In pathway A, the first step (a)
is the coupling of carbene groups derived from EDA to
give olefin 16, a reaction that is well-established in our
previous work [25]. The second step (b) is a Michael
addition of piperidine to 16 to give 17; we have shown that
this reaction occurs in 100% yield in the absence of the
gold catalyst under the conditions of reaction (6). The final
step (c) in pathway A is the oxidative-dehydrogenation of
H
PhOC
N
COPh
H
O
N
Au, O2, –H2O
N2
2
+
Ph
CH3CN, 60 °C
90% yield
(11)
(12)
(E)-11
O
PhOC
BuHN
H
Au, O2, –H2O
+ n-BuNH2
N2
2
Ph
CH3CN, 60 °C
85% yield
COPh
12
(Z)-
O
+
Ph
Au, O2
N2
PhOC
+
O
Ph
PhOC
COPh
+
Me
(13)
CH3CN, 60 °C
N
COPh
PhNH2
13
14
13
trans-
cis-
17 to give (E)-1. Unfortunately, this conversion did not
occur under the conditions of the reaction, which suggests
that A is not a likely pathway for reaction (6). In pathway
Other diazo compounds were also investigated. The
reaction of phenyl diazomethane PhCH=N2 with piperidine
gave a 70% yield of stilbene PhCH=CHPh (cis/trans 1:1)
under the standard conditions; no enamine or N–H inser-
tion products were observed. This yield of stilbene is sig-
nificantly lower than that (92% yield) obtained in the gold-
catalyzed reaction of PhCH=N2 in the absence of piperi-
dine [25] under the same conditions. In contrast to the
reactions above, methyl (4-methylphenyl)diazoacetate
(Me-MPDA) and methyl (4-methoxylphenyl)diazoacetate
(MeO-MPDA) react with amines to give N–H insertion
products under the same conditions. For example, the
reaction of Me-MPDA with piperidine provided a 50%
yield of product 15 and some other uncharacterized
byproducts (Eq. 14). But this reaction also gave a 66%
yield of 15 even in the absence of the gold catalyst under
the same conditions. Although this reaction has been
Au
a
( )
EtO2CCHN2
EtO2CCH=CHCO2Et
A
Au
–
16
O2, H2O
B
d
( )
EtO2CC CCO2Et
C
b
( )
N
N
H
f
( )
H
N
H
e
( )
Au
EtO2C
N
CO2Et
Au, O2
–H2O
EtO2C H CO2Et
H
EtO2C
Au, O2
EDA
g
( )
N
N
H
18
c
( )
(E)-1
17
Scheme 2 Plausible mechanisms for gold powder-catalyzed reaction
of EDA with piperidine and O2 (Eq. 6)
123

14
Y. Zhou et al.
B, the oxidative-dehydrogenation of EDA in step (d) is
followed by amine addition (e) to DEAD to give the
product. Although the latter reaction (e) is well-known as
described above (Eq. 10) and in reference [64–69], step (d)
does not occur as shown in the gold-catalyzed reaction of
EDA in the absence of amine; this reaction gives the car-
bene coupled products (Eq. 2) [25]. Thus, pathway B is
also unlikely. In pathway C, the first step (f) involves N–H
insertion, which is plausible because of the known insertion
reaction (Eq. 14) of Me-MPDA with piperidine. However,
the conversion of this product 18 to (E)-1 does not occur
under the conditions of the reaction. Thus, none of the
pathways, A, B, or C, is consistent with the experimental
results.
4 Conclusion
The bulk gold-catalyzed reactions of diazoalkanes with
amines and O2 described in this paper show that the gold
metal need not be nanosized in order to be a highly active
catalyst. These reactions represent a fundamentally new
type of reaction that is catalyzed by bulk gold. Moreover,
the enamine products are different than the N–H insertion
products that are obtained when the same reactants are
combined in the presence of transition metal complex or
copper metal catalysts. Formation of the enamine products
is facilitated by electron-withdrawing groups (–CO2Et and
–C(O)Ph) in the diazoalkane and by nucleophilic amines. A
mechanism involving amine attack on a surface-adsorbed
carbene group, e.g.,:C(H)(CO2Et), is consistent with these
trends. If the amine attack is slow, other products resulting
from coupling of the carbene groups or oxidative-dehy-
drogenation of the amines are formed. These fundamental
studies using a gold powder catalyst suggest that bulk gold
supported on a high surface area material could be used as
a practical catalyst of these reactions. No other catalysts of
these reactions have been previously reported.
While it is possible to write other mechanisms for the
reaction in Eq. 6, they would be highly speculative.
However, trends in the reactivities of different diazoalk-
anes and amines are consistent with a key step in the
mechanism that involves amine attack on a surface carbene
(Scheme 3), analogous to reactions of transition metal
carbene complexes with amines (Eq. 3). If the amine is not
sufficiently nucleophilic, this step is slower than coupling
of two carbene groups to form the EtO2CCH=CHCO2Et
isomeric products (Eq. 2). Thus, there is no reaction of
EDA with the weakly nucleophilic anilines, PhNH2 and p-
Me2NC6H4NH2 (Table 2, entries 10 and 11). On the other
hand, the more nucleophilic aliphatic amines (Table 2)
give enamine products, presumably because their addition
to the surface carbene is faster than the coupling of two
carbene groups. The tendency of carbene groups to be
attacked appears to depend on the presence of an electron-
withdrawing group such as –CO2Et or –C(O)Ph as both
EDA and PhCOCH=N2 give enamine products with
piperidine (Eqs. 6 and 11). On the other hand, the reaction
of PhCH=N2, lacking an electron-withdrawing group, with
piperidine gives none of the enamine but only stilbene
(PhHC=CHPh) resulting from coupling of carbene groups
and an oxazole resulting from reaction of the carbene with
the acetonitrile solvent (Eq. 13).
Acknowledgments This research was supported by the U.S.
Department of Energy under contract No. DE-AC02-07CH11358
with Iowa State University and funds from NSF grant CHE-0809901.
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