Yttrium (amidate) complexes for catalytic C-N bond formation. Rapid, room temperature amidation of aldehydes

Article abstract of DOI:10.1039/c2dt30214d

Yttrium (amidate) precatalysts are highly active for the mild amidation of aldehydes with amines. Reactions occur at room temperature within 5 min in up to 98% isolated yield. These rare-earth systems are effective for this transformation in the absence of supplementary heat, light, base, or oxidants. The reaction proceeds with functionalized amines and/or aldehydes. A comparison of various amidate precatalysts in combination with reaction monitoring suggests that the targeted amide products formed during the reaction promote the formation of alternative catalytically active amidate species in situ.

Full text of DOI:10.1039/c2dt30214d

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PAPER
Yttrium (amidate) complexes for catalytic C–N bond formation. Rapid, room
temperature amidation of aldehydes
Jaclyn A. Thomson and Laurel L. Schafer*
Received 28th January 2012, Accepted 13th March 2012
DOI: 10.1039/c2dt30214d
Yttrium (amidate) precatalysts are highly active for the mild amidation of aldehydes with amines.
Reactions occur at room temperature within 5 min in up to 98% isolated yield. These rare-earth systems
are effective for this transformation in the absence of supplementary heat, light, base, or oxidants. The
reaction proceeds with functionalized amines and/or aldehydes. A comparison of various amidate
precatalysts in combination with reaction monitoring suggests that the targeted amide products formed
during the reaction promote the formation of alternative catalytically active amidate species in situ.
More interestingly, various metal-based catalysts have been
Introduction
shown to promote this transformation. For example, simple
nickel salts can be used,16 and palladium is also an effective cat-
The amide functionality appears in molecules across chemistry
alyst in the presence of hydrogen peroxide.17 Alternatively,
and biochemistry, and can be found in natural products, pharma-
ceuticals, polymers, and proteins.1 Amides are typically syn-
ruthenium hydrides in combination with sodium hydride effect
thesized from amines with acid chlorides or carboxylic acids,
however, these functional groups can be difficult to install if
other sensitive functionalities are present in the molecules. In
addition, many of these reactions require stoichiometric coupling
reagents, yielding side products that present challenges during
product isolation. The inherent problems and waste associated
with these transformations leave a niche for a milder, more inex-
pensive reaction protocol. Indeed the development of catalytic
routes to access amide products is an area of intense investi-
gation,2 with many recent contributions focusing on the appli-
cation of alcohols and amines as precursor substrates.3–6 An
alternative approach is the direct amidation of aldehydes7 with
amines, which is attractive due to the availability and inexpen-
sive nature of the simple starting materials.
The amidation of aldehydes has garnered significant interest
in recent years and a variety of reaction conditions have been
reported for this transformation. Several groups have reported
methods using metal free conditions including N-heterocyclic
carbenes (NHCs)4,8 as organocatalysts in combination with stoi-
chiometric reagents or tert-butylhydrogenperoxide (TBHP) as
stoichiometric oxidant.9,10 While metal-free reactions can be
attractive, these systems result in substantial waste generation.
Radical and light initiated amidations requiring either stoichio-
metric additives or long reaction times have been reported.11,12
Some examples use stoichiometric amounts of non-transition
metals, such as the use of lithium diisopropylamide (LDA) in a
Cannizzaro type reaction,13 or the use of sodium hydride and an
oxidative mixture of potassium iodide/TBHP respectively.14,15
this transformation or copper–silver with hydrochloride salts can
give the desired amide products in 28–92% yield.18,19 These
examples establish the utility of metal-catalyzed transformations,
however the potential to use metals with a reduced toxicity
profile, such as the rare-earth elements, is an attractive
alternative.
Of interest to our program is the fact that a number of rare-
earth systems are known catalysts for this reaction, and to this
end the Marks20 group found that simple, commercially available
rare-earth amido complexes easily promote this transformation.
More recently, the Wang group showed that aldehyde amidation
is easily facilitated using custom prepared rare-earth metal amido
complexes21 or by Cannizzaro-type reactions22 using rare-earth
chlorides. Also, the Shen group has described the transformation
using a number of rare-earth guanidinate,23,24 amidinate,25 and
heterobimetallic26–28 complexes. Most importantly, all of the
rare-earth catalysts disclosed do not require any additional bases
or oxidants, making for attractive reaction conditions for this
desirable transformation.
Amidate complexes of rare-earth and early transition metals
have been shown to be effective catalysts for a variety of trans-
formations. Rare-earth and group 4 (amidate) complexes can be
used for the intermolecular and intramolecular hydroamination
of alkynes,29–31 allenes,32,33 and alkenes.29,34–41 Simple amidate
complexes can also promote hydroaminoalkylation in an intra-
molecular and intermolecular fashion.40,42–45 Finally, rare-earth
(amidate) complexes can be used for the ring-opening polymer-
ization of lactones, to yield biodegradable polyester
materials.39,46,47 To further assess the potential application of
these easily accessed complexes, here we report the use of rare-
earth (amidate) complexes for the amidation of aldehydes with
amines, a catalytic C–N bond forming reaction. We show that
Department of Chemistry, University of British Columbia, 2036 Main
Mall, Vancouver, British Columbia V6T 1Z1, Canada. E-mail:
Schafer@chem.ubc.ca
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yttrium (amidate) complexes are highly active precatalysts for
this transformation with a variety of aldehydes and amines. Most
importantly, they mediate the reaction without added oxidants,
bases, heat, or light in very short reaction times. Interestingly, the
amide products of this catalytic transformation are the protonated
version of our precatalyst amidate ligands, suggesting the possi-
bility that most rare-earth precatalysts used to date could have
the resultant amide products involved in the evolving catalyti-
cally actives species in situ.
previously reported for a variety of rare-earth elements.49,50
Thus, based upon the proposed catalytic mechanism, 3 equiva-
lents of aldehyde are required for catalytic turnover. Furthermore,
while Scheme 1 illustrates amide, alcohol and ester product for-
mation in the catalytic cycle, it cannot be overlooked that sec-
ondary amide products and alcohols could be deprotonated
in situ to yield a variety of evolving catalytically relevant
species, including Ln(amidate) complexes. As an initial starting
point for these investigations we applied previously reported
reaction conditions23–28 to investigate the potential impact of
varied steric and electronic properties of amidate precatalysts for
this transformation.
Several mono-, bis-, and tris(amidate) complexes of yttrium
have been disclosed in the literature.46–48 These complexes are
easily formed through the protonolysis of Y(N(SiMe)3)2)3 with
the appropriate amide proligand. Simple control of the metal :
proligand stoichiometry and the temperature of the reaction
cleanly forms complexes containing one, two, or three amidate
ligands (Chart 1).46,48 These amidate complexes have been
Results and discussion
Reaction conditions and catalyst optimization
In 2008 the Marks group reported the use of rare-earth amido
complexes of the type Ln(N(SiMe3)2)3 for the amidation of alde-
hydes.20 In these investigations, the large ionic radius of La in
La(N(SiMe3)2)3 was found to be the preferred amido complex
for this reaction and indeed showed promise as a general catalyst
for this desirable transformation. Encouraged by these results
and the observation that the products of this reaction are directly
related to the yttrium (amidate) complexes previously disclosed
for catalytic C–N bond formation via hydroamination,48 we
endeavoured to investigate yttrium (amidate) complexes for the
direct amidation of aldehydes.
A mechanism (Scheme 1) has been proposed for the rare-earth
catalyzed amidation of aldehydes,20 which invokes aldehyde (A)
as the oxidant, yielding the desired amide and alcohol (B) as
final products. This alcohol product is non-innocent in this trans-
formation, as it can also act as a nucleophile toward Lewis-acid
activated aldehydes to generate ester by-product (C), via the
related Tischenko reaction.20 This reaction has also been
Chart 1 Mono-, bis-, and tris(amidate) complexes of yttrium.
Scheme 1 Proposed catalytic cycle for Y(N(SiMe3)2)3 mediated aldehyde and amine amidation.20
7898 | Dalton Trans., 2012, 41, 7897–7904
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Table 1 Optimized reaction times and isolated product yields using
various yttrium precatalysts for the amidation of aldehydes with amines
Chart 2 Tris(amidate) complexes of yttrium.
Entry
Time (min)
Complex
Yielda (%)
1
2
3
4
5
6
7
8
9
5
1
2
3
4
5
6
7
8
74
46
25
58
54
32
58
51
30
72
yttrium tris(amidate) complexes are more effective precatalysts
for the amidation reaction and the somewhat electron-withdraw-
ing naphthyl substituent on the amidate ligand is preferred over
the tert-butyl substituent (Chart 1).
15
30
45
30
30
45
60
60
60
Once it was determined that the tris(amidate) complexes of
yttrium are the most effective amidate catalysts for the transform-
ation, a series of tris(amidate) complexes have been synthesized
and tested to further examine the effect of ligand steric and elec-
tronic properties on the reaction. It has been determined by com-
paring 1 and 4 that changing the aromatic naphthyl backbone for
an aliphatic tert-butyl resulted in a decrease in yield (entries 1
and 4, Table 1). By comparing complexes 4 and 7 it was found
that decreasing the steric bulk on the nitrogen substituent of the
amidate had no effect on the product yield (entries 4 and 7,
Table 1). Finally, the ligand electronic properties were investi-
gated using complexes 8 and 9, where addition of trifluoro-
methyl groups and therefore an increase in the electronic-
withdrawing nature of the amidate backbone results in a decrease
in yield (entries 8 and 9, Table 1). Most interestingly, for com-
parison purposes, the starting material used to synthesize all the
yttrium (amidate) complexes, Y(N(SiMe3)2)3, has also been
tested for catalytic activity using our established experimental
protocol.52 As shown in entry 10, the product is obtained in
good overall yield (72%) but requires 60 min to complete the
transformation.
9
10
Y(N(SiMe3)2)3
a Isolated yields.
chosen based on their previously reported catalytic behaviour in
C–N bond forming reactions,48 and also the variation of alkyl
and aryl substituents on the carbonyl. By varying the number of
amidate ligands incorporated into the precatalyst we can explore
the effect of steric bulk due to the varied coordination environ-
ment of the metal center. Given the ease of formation of these
known amidate complexes from Y(N(SiMe)3)2)3, which has
been shown to be a suitable catalyst for aldehyde amidation by
Marks and Seo,20 one could postulate that amidate complexes
could be formed in situ as the reaction proceeds.
Investigations into the room temperature amidation of alde-
hydes immediately revealed very short reaction times, with com-
plete conversions being observed in <15 min in some cases.
These short reaction times are remarkable, as these transform-
ations have been previously reported in terms of hours, not
minutes.7 Thus initial experiments focused on monitoring the
reactions by taking aliquots every 5–10 min to determine the
shortest reaction time required for a 1.00 mmol scale catalytic
reaction (amine limiting reagent) to go to completion
(Table 1).51 With the optimized time determined, the 1.00 mmol
scale reaction has been rerun to determine an isolated yield. It
should be noted that increased reaction times did not improve
product yields, due to various side reactions known to consume
starting material, such as imine formation, in this transformation
(vide infra). Catalyst 1 forms N-p-tolylbenzamide from benz-
aldehyde and p-toluidine in 74% yield at room temperature in
just 5 min (entry 1, Table 1). Literature precedence suggests that
the optimal ratio of aldehyde (A) to amine is 3 : 120 and attempts
to improve reaction yields by adjusting the ratios of aldehyde to
amine (e.g. 1 : 1, 1 : 3) showed that indeed the 3 : 1 ratio is the
preferred stoichiometry for amidate precatalysts as well. In the
case of complexes 1–3, the yield of the amide product increased
with the number of amidate ligands coordinated to the catalyst,
and the preferred reaction time is decreased with an increase in
coordinated amidate ligands. In the case of complexes 4–6, the
product yield increases with the number of amidates coordinated
to the complexes though the reaction times do not vary signifi-
cantly (entries 4–6, Table 1). These results indicate that the
Substrate scope
Using the optimized reaction conditions and preferred precatalyst
identified (1), the scope of the amidation reaction has been inves-
tigated (Table 2). Current rare-earth catalytic systems have been
shown to be highly effective with aryl substituted aldehydes and
amines, however, these reactions require much longer reaction
times (2 to 48 h) and often high temperatures (up to 65 °C).20–28
In addition, there are very few catalysts capable of tolerating
alkyl substituents. Cyclohexylcarboxaldehyde is mildly toler-
ated,20,24,27 but rare-earth catalysts are thus far unreported for
other alkyl substituted aldehyde substrates. The other notable
challenge for the substrate scope of this transformation is that
only a few complexes are capable of tolerating steric bulk.21,22
Here, the formation of the desired amidation product with 1
occurs effectively and rapidly at room temperature with a variety
of substrates in good to excellent yield.
Initial investigations probed the nature of amines that can be
used in combination with precatalyst 1. Various aryl primary
amines can be used (entries 1–3, Table 2) and the presence of
aryl-halides can be used without complication. These results are
similar to those previously reported for other rare-earth
complexes,20,23–28 however, one interesting result is the
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Table 2 Catalytic amidation of various aldehydes with amines
been rarely reported for this transformation using a rare-earth cat-
alyst,20,24,27 and this is the first report of a rare-earth complex in
combination with pivalaldehyde. Electronic effects of the alde-
hyde substrates have also been probed and observations are con-
sistent with previous reports,20,22–28 in which the strongly
electron-withdrawing nitro- or even the chloro substituent
enhance reactivity (entries 9–12). However, the strongly donat-
ing methoxy-substitutent dramatically reduces reactivity (entry
13), such that low yields are obtained even with the favourable
piperidine amine reaction partner. These general trends are in
keeping with previously observed reactivity profiles,23,25,26
however the modest tolerance for sterically demanding amines
and aldehydes suggest that amidate precatalysts have an accom-
modating steric environment about the catalytically active metal
center, likely due to the known hemi-lability of the amidate
ligand framework.53
In summary, yttrium (amidate) precatalyst 1 can be used in
combination with electronically varied aldehydes with aryl
primary amines as well as electronically varied secondary
amines. Direct comparison of other previously reported rare-
earth amido complexes and complex 1 using the reaction of
benzaldehyde and N-methylbenzylamine showed that 1 is con-
sistent with the preferred larger lanthanum amido complex, in
terms of isolated yields obtained, but superior with respect to
dramatically shortened reaction times.20,22,23
Entry
R
Amine
Yielda
(%)
1
2
3
Ph
Ph
Ph
74
64
80
4
5
Ph
Ph
22
74
6
7
Ph
Ph
83
78
8
tBu
21
9
10
4-Nitrophenyl
4-Nitrophenyl
84
87
Mechanistic insight
Using the proposed mechanism put forth by Marks and Seo
(Scheme 1)20 as a guiding hypothesis, experiments have been
pursued to probe the reaction with yttrium amidate (1) as pre-
catalyst. The mechanistic proposal suggests three side products
are produced during the catalytic cycle: an alcohol (B), an ester
(C), and an imine (D) (Scheme 1). While monitoring the cataly-
11
12
13
14
4-Nitrophenyl
4-Chlorophenyl
4-Methoxyphenyl
Cyclohexyl
98
85
27
84
15
Cyclohexyl
H2NPh
35
1
a Isolated yields.
tic reaction shown in Table 1 by H NMR spectroscopy, the for-
mation of benzyl alcohol could be readily identified due to the
appearance of the new benzylic proton signals at 4.70 ppm in
CDCl3. Furthermore, the formation of multiple products with
overlapping signals in the 2.35–2.45 ppm region of the spectrum
suggested imine and product formation were occurring simul-
taneously. To confirm their formation, each of the aforemen-
tioned products were prepared using traditional methods54 and
their spectral data compared directly to spectra obtained during
reaction monitoring. Indeed the presence of amide, ester and
imine products could all be confirmed.
observation that steric bulk can be tolerated (entry 4). While the
desired product is obtained in modest yield, it is noteworthy that
2,6-dimethylaniline has rarely been disclosed as a productive
amidation substrate.22,26 Also consistent with other rare-earth
amidate precatalysts, aliphatic primary amines cannot be used in
combination with amidate precatalysts, presumably due to com-
peting imine formation (Scheme 1, vide infra). However, second-
ary amines are excellent substrates for this transformation and
both aliphatic and aryl substituted secondary amines result in
some of the highest yields observed with this catalyst system
(entries 5–7).
While electronic effects of the amine substrates are minimal
(entries 1–3), the steric effects are substantial (entry 4). This is
mirrored in the observed reactivity with aldehydes as well, such
that the sterically demanding tert-butyl substituent of pivalalde-
hyde has limited reactivity, even with a known reactive amine
partner. However, this reduced reactivity seems to be due to both
steric and electronic effects considering that cyclohexylcarbox-
aldehyde undergoes amidation in modest yield with aniline but
is an excellent reaction partner with piperidine (entries 15 and
14, respectively). The use of cyclohexylcarboxaldehyde has
In a control reaction of benzaldehyde and p-toluidene, in the
absence of any catalyst, imine is observed to from in low yield at
room temperature.55 Such Schiff Base condensations can be pro-
moted by Lewis acids, which may further enhance their pro-
duction under catalytic conditions.56 For the reaction of
benzaldehyde and p-toluidine, imine formation during the cataly-
tic amidation reaction is observed by the diagnostic signals at
1
2.39 ppm for the methyl protons present in the H NMR spectra
(in CDCl3), as well as the M = 196 m/z signal present in the
mass spectrum of the crude reaction mixture. Furthermore, diag-
nostic MS signals for imine formation have been found in all
cases where primary aryl amine has been used as a substrate.
This side reaction not only consumes the limiting amine reagent,
but also results in the formation of water, which when released
7900 | Dalton Trans., 2012, 41, 7897–7904
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Scheme 2 Tishchenko reaction using 1.
during the reaction may decompose the catalytically active
yttrium complexes and thus may be a contributing factor to the
lower yields obtained for those reactions with primary amines
(entries 1–3, Table 2). One way to prevent this side reactivity is
to use a secondary amine, and indeed the yield of products
obtained with secondary amine substrates is significantly
increased (entries 5–7 and 11–14, Table 2).
Fig. 1 Reaction of p-toluidine with benzaldehyde with Y(N-
(SiMe)3)2)3.
The presence of ester product is noted by the appearance of a
diagnostic singlet at 5.37 ppm while monitoring the reaction by
1H NMR spectroscopy. This observation and literature pre-
cedence23 suggest that the yttrium (amidate) complexes may also
be capable of independently synthesizing the ester product from
aldehydes. Indeed complex 1 can be used for the Tishchenko
reaction with benzaldehyde to give benzyl benzoate in good
yield (Scheme 2).49,50
Thus, aldehyde amidation using 1 as a precatalyst affords not
only the desired product, but also alcohol, imine and ester side
products. Notably both the alcohol and the amide products of
this catalytic transformation are protic and in situ can become
alkoxide and amidate ligands, respectively. Indeed, by the com-
pletion of the catalytic reaction, only free N-(2,6-diisopropylphe-
nyl)naphthylamide proligand can be observed by 1H NMR
spectroscopy. It has been previously reported46,48 that the ortho-
naphthyl signal shifts significantly from free ligand (8.86 ppm)
upon complexation (>9 ppm). This diagnostic signal can even be
used to discern whether the complex is a mono-, bis-, or tris-
(amidate) complex as the signal shifts to 9.16, 9.09, and
9.26 ppm, respectively, in d6-benzene.46,48 However, only free
ligand is discernible and this is consistent with ligand exchange
reactions in rare-earth amidate complexes, which have been pre-
viously observed.48
One notable difference in the application of 1 and Y(N
(SiMe3)2)3 in the reaction of benzaldehyde and p-toluidine is the
rapid reaction completion when precatalyst 1 is used (within
5 min) while Y(N(SiMe3)2)3 requires 60 min to reach compar-
able reaction yields. Upon monitoring of reaction progress with
Y(N(SiMe3)2)3 as the precatalyst, a clear induction period is
observed, followed by a spike in reactivity (Fig. 1). These obser-
vations suggest that in situ species, which may include yttrium
(amidate) complexes, have dramatically enhanced reactivity over
Y(N(SiMe3)2)3 precatalyst. These results are also consistent with
the observation that mono and bis amidate complexes 2 and 3
have reduced reactivity compared to tris(amidate) complex 1.
Thus, by using the preformed tris(amidate) precatalyst, the sig-
nificant induction period is avoided, resulting in very short reac-
tion times of only 5 min.
temperature in only 5 min. Preforming an amidate complex
avoids the induction period that occurs when a slower reacting
amido complex is used as precatalyst. Complex 1 is functional
group tolerant, effectively forming products with electron-with-
drawing and electron-donating substituents on both the alde-
hydes and amines. Tolerant of both primary and secondary
amines, 1 is one of only a few examples of a rare-earth complex
tolerating steric bulk on a primary amine. In addition to tolerat-
ing aryl aldehydes, complex 1 is an effective catalyst for ali-
phatic aldehydes, including pivalaldehyde a substrate thus far
unreported by a rare-earth system. These insights into in situ cat-
alyst activation and ligand design provide guidance for develop-
ment of improved catalytic systems for this transformation.
Experimental section
All operations were performed under an inert atmosphere of
nitrogen using standard Schlenk-line or glovebox techniques.
Tetrahydrofuran (THF), toluene, and hexanes were purified by
passage through an alumina column and sparged with nitrogen.
Dichloromethane (DCM), benzaldehyde, aniline, 2,6-dimethyl-
aniline, piperidine, N-methylaniline, N-methylbenzylamine,
pivalaldehyde, and cyclohexylcarboxaldehyde were purified by
distillation and stored over molecular sieves. p-Toluidine, p-
chloroaniline, 4-nitrobenzaldehyde, 4-chlorobenzaldehyde, and
p-anisaldehyde were purified by sublimation. Y(N(SiMe3)2)3
was synthesized as described in the literature.57 The compounds
tris(N-2′,6′-diisopropylphenyl(naphthyl)amidate)yttrium mono
(tetrahydrofuran) (1),46 tris(N-2′,6′-dimethylphenyl(tert-butyl)-
amidate)yttrium mono(tetrahydrofuran) (7),46 tris(N-2′,6′-diiso-
propylphenyl(p-(trifluoromethylphenyl)amidate)yttrium mono-
(tetrahydrofuran) (8),46 bis(N-2′,6′-diisopropylphenyl(naphthyl)
amidate)mono(trimethylsilylamido)yttrium
mono(tetrahydro-
furan) (2),48 mono(N-2′,6′-diisopropylphenyl(naphthyl)amidate)-
bis(trimethylsilylamido)yttrium mono(tetrahydrofuran) (3),48 N-
(2,6-diisopropylphenyl)tert-butyl amide, and N-(2,6-diisopropyl-
phenyl)(3,5-bis(trifluoromethyl))phenylamide48 were made
according to previously reported procedures. All other com-
pounds were commercially available and used as received unless
otherwise stated. 1H and 13C NMR spectra were recorded on
Bruker AV300, AV400, and AV600 spectrometers at 298 K.
Chemical shifts are reported in parts per million and referenced
to residual solvent. All 13C NMR spectra were proton-decoupled.
Conclusions
In summary, a yttrium (amidate) precatalyst has been found for
the amidation of aldehydes under mild conditions at room
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Synthesis of mono(N-2′,6′-diisopropylphenyl(tert-butyl)amidate)-
bis(trimethylsilylamido)yttrium mono(tetrahydrofuran) (6)
Elemental analysis and mass spectra were performed by the
microanalytical laboratory of the Department of Chemistry at the
University of British Columbia.
Inside a nitrogen filled glovebox, yttrium tris(bis(trimethylsilyl)-
amide) (0.219 g, 0.384 mmol) was dissolved in 5 mL of tetra-
hydrofuran with a stirbar in a 100 mL reaction vessel. Once the
solid was dissolved, a solution of N-(2,6-diisopropylphenyl)tert-
butyl amide (0.100 g, 0.384 mmol) dissolved in 5 mL of tetra-
hydrofuran and added dropwise. The solution was stirred within
the glovebox for 2 h at room temperature and then filtered
through Celite and concentrated under reduced pressure to a give
white solid. The product was recrystallized by dissolving in
hexanes and leaving at −30 °C to give a white crystalline solid.
Yield: 0.234 g, 82%. The reported yield is the combination of
inseparable geometric isomers. 1H NMR (400 MHz, C6D6
mixture of two compounds a and b in a ∼ 1 : 2 ratio): δ 7.08 (s,
1H, aryl-H, a), 7.01 (s, 2H, aryl-H, a), 7.00 (s, 2H, aryl-H, b),
6.70 (m, 1H, aryl-H, b), 3.81 (broad s, 4H, O–CH2), 3.39
(septet, 2H, J = 6 Hz, CH(CH3)2, a), 3.25 (septet, 2H, J = 6 Hz,
CH(CH3)2, b), 1.42 (d, 6H, J = 6 Hz, CH(CH3)2, a), 1.34 (d,
6H, J = 6 Hz, CH(CH3)2, a), 1.31 (d, 10H, J = 6 Hz, CH(CH3)2,
b overlapping with O–CH2CH2), 1.22 (d, 15H, J = 6 Hz, CH
(CH3)2 for b overlapping with C(CH3)3 for a), 1.10 (s, 9H, C
(CH3)3 for b), 0.36 (s, 36H for a, 36H for b, N(Si(CH3)3)2 for
both a and b). 13C NMR (150.9 MHz, C6D6 broad and
complex): δ 186.3 (CvO), 140.7, 140.6, 124.7, 124.2, 123.1
(br), 121.4 (br), 120.5 (br) (aryl-C’s), 71.2 (O–CH2), 41.7 (O–
CH2CH2), 29.5 (br), 28.6 (br), 27.9, 27.6 (br), 25.4 (br), 24.9
(br), 24.1 (br), 23.6 (br) 22.9 (br), 21.6 (br) (CH(CH3)2 and C
(CH3)3), 5.12 (br), 4.34 (br) (N(Si(CH3)3)2). IR data (KBr,
cm−1): 2961 (s), 1513 (s), 1477 (s), 1399 (s), 1348 (s), 1313
(w), 1246 (s), 1176 (w), 942 (s), 830 (s), 767 (w) cm−1. EIMS
(m/z): 669 [M+], 654 [M+ − CH3], 509 [M+ − N(Si(CH3)3)2].
Anal. Found (calcd for C33H70N3O2Si4Y): C 52.35% (53.40%),
N 5.48% (5.66%), H 9.11% (9.51%).
Synthesis of tris(N-2′,6′-diisopropylphenyl(tert-butyl)amidate)-
yttrium mono(tetrahydrofuran) (4)
Inside a nitrogen filled glovebox, yttrium tris(bis(trimethylsilyl)-
amide) (0.146 g, 0.256 mmol) was dissolved in 5 mL of tetra-
hydrofuran with a stirbar in a 100 mL reaction vessel. Once the
solid was dissolved, a solution of N-(2,6-diisopropylphenyl)tert-
butyl amide (0.200 g, 0.766 mmol) dissolved in 5 mL of tetra-
hydrofuran was added dropwise. The solution was stirred within
the glovebox for 2 h at 65 °C and then filtered through Celite
and concentrated under reduced pressure to a give white solid.
The product was recrystallized by dissolving in hexanes and
leaving at −30 °C to give a white crystalline solid. Yield:
0.207 g, 91%. 1H NMR (600 MHz, C6D6): δ 7.07 (broad m, 9H,
aryl-H), 3.46 (broad s, 4H, O–CH2), 3.07 (broad m, 6H, CH
(CH3)2), 1.46 (broad s, 4H, O–CH2CH2), 1.34 (d, J = 6 Hz,
18H, CH(CH3)2), 1.12 (overlapping d and s, 27H, CH(CH3)2
and C(CH3)3). 13C NMR (100.6 MHz, C6D6): δ 186.3 (CvO),
140.7, 124.7, 122.8, 121.5 (aryl-C), 69.2 (O–CH2), 41.6 (O–
CH2CH2), 25.0 (CH(CH3)2), 28.7 (C(CH3)3), 25.0 (CH3), 23.0
(CH3). IR data (KBr, cm−1): 2961 (s), 2861 (w), 1618 (s), 1508
(s), 1474 (s), 1395 (w), 1351 (w), 1213 (w), 931 (w), 805 (w)
cm−1. EIMS (m/z): 869 [M+], 686 [M+ − tBu[O,N]Dipp], 261
[tBu[O,N]Dipp]. Anal. Found (calcd for C55H86N3O4Y): C
69.19% (70.11%), N 4.52% (4.46%), H 9.20% (9.26%).
Synthesis of bis(N-2′,6′-diisopropylphenyl(tert-butyl)amidate)-
mono(trimethylsilylamido)yttrium mono(tetrahydrofuran) (5)
Inside a nitrogen filled glovebox, yttrium tris(bis(trimethylsilyl)
amide) (0.232 g, 0.408 mmol) was dissolved in 5 mL of tetra-
hydrofuran with a stirbar in a 100 mL reaction vessel. Once the
solid was dissolved, a solution of N-(2,6-diisopropylphenyl)tert-
butyl amide (0.213 g, 0.815 mmol) dissolved in 5 mL of tetra-
hydrofuran and added dropwise. The solution was stirred within
the glovebox for 2 h at 65 °C and then filtered through Celite
and concentrated under reduced pressure to a give white solid.
The solid was redissolved in toluene and stirred at 90 °C for a
subsequent 2 h. The product was then concentrated again to a
white solid and recrystallized by dissolving in hexanes with a
few drops of toluene and leaving at −30 °C to give a white crys-
talline solid. Yield: 0.288 g, 84%. 1H NMR (300 MHz, C6D6): δ
7.20 (broad m, 6H, aryl-H), 3.40 (broad s, 4H, O–CH2), 3.13
(broad m, 4H, CH(CH3)2), 1.33 (overlapping: d, J = 6 Hz, 12H,
CH(CH3)2, and broad s, 4H, O–CH2CH2), 1.08 (overlapping d
and s, 30H, CH(CH3)2 and C(CH3)3), 0.51(s, 18H N(Si-
(CH3)3)2). 13C NMR (100.6 MHz, C6D6): δ 182.3(CvO),
141.2, 124.6, 124.5, 123.1 (aryl-C), 69.6 (O–CH2), 42.1 (O–
CH2CH2), 23.4 (CH(CH3)2), 28.8 (C(CH3)3), 25.5 (CH3), 24.9
(CH3), 2.39 (N(Si(CH3)3)2). Anal. Found (calcd for
C44H78N3O3Si2Y): C 63.11% (62.75%), N 5.30% (4.99%), H
9.22% (9.34%).
Synthesis of tris(N-2′,6′-diisopropylphenyl((3,5-bis-
(trifluoromethyl)-phenyl)amidate)yttrium mono-
(tetrahydrofuran) (9)
Inside a nitrogen filled glovebox, yttrium tris(bis(trimethylsilyl)-
amide) (0.0918 g, 0.161 mmol) was dissolved in 5 mL of tetra-
hydrofuran with a stirbar in a 100 mL reaction vessel. Once the
solid was dissolved, a solution of N-(2,6-diisopropylphenyl)(3,5-
bis(trifluoromethyl))phenylamide (0.200 g, 0.479 mmol) dis-
solved in 5 mL of tetrahydrofuran and added dropwise. The sol-
ution was stirred within the glovebox for 2 h at 65 °C and then
filtered through Celite and concentrated under reduced pressure
to a give white solid. The product was recrystallized by dissol-
ving in hexanes and leaving at −30 °C to give a white crystalline
1
solid. Yield: 0.200 g, 88%. H NMR (400 MHz, C6D6): δ 8.05
(s, 6H, aryl-H), 7.61 (d, J = 8 Hz, 3H, aryl-H), 7.10 (m, 3H,
aryl-H), 7.04 (m, 6H, aryl-H), 3.71 (broad s, 4H, O–CH2), 3.38
(broad m, 6H, CH(CH3)2), 1.32 (m, 4H, O–CH2CH2), 1.04
(broad s, 18H, CH(CH3)2), 0.83 (d, 18H, J = 7 Hz, CH(CH3)2).
13C NMR (100.6 MHz, C6D6): δ 170.3 (CvO), 136.9, 130.9,
130.1, 128.9, 124.8, 124.5, 123.6, 121.2 (aryl-C), 131.52 (q, J =
34 Hz, CF3), 67.93 (O–CH2), 29.11 (CH(CH3)2), 28.60 (O–
CH2CH2), 25.50 (CH3), 24.26 (CH3). IR data (KBr, cm−1): 2966
7902 | Dalton Trans., 2012, 41, 7897–7904
This journal is © The Royal Society of Chemistry 2012

View Article Online
N-(4-Chlorophenyl)benzamide (Table 2, entry 3)
(w), 1534 (s), 1459 (s), 1351 (s), 1278(s), 1187 (w), 1137 (s),
1066 (s), 909 (w), 847 (s), 800 (w), 702 (w) cm−1. EIMS (m/z):
1337 [M+], 925 [M+ − 3,5-bis(CF3)phenyl[O,N]Dipp], 417
[3,5-bis(CF3)phenyl[O,N]Dipp]. Anal. Found (calcd for
C67H68F18N3O4Y): C 56.90% (57.07%), N 3.16% (2.98%), H
4.82% (4.86%).
Purified by column chromatography (8 : 1 petroleum ether : ethyl
acetate) yielding 0.182 g (80%). Spectral data matched literature
references.59
N-(2,6-Dimethylphenyl)benzamide (Table 2, entry 4)
General procedure for catalytic amidation
Purified by column chromatography (8 : 1 petroleum ether : ethyl
acetate) yielding 0.048 g (22%). Spectral data matched literature
references.22
Inside a nitrogen filled glovebox, a 20 mL vial was charged with
yttrium (amidate) complex (0.05 mmol), amine (1.00 mmol),
2.5 mL toluene, and a stir bar. Benzaldehyde (3.00 mmol) was
added by syringe to the stirring solution and the mixture was left
to stir before the vial was removed from the glove box and
10 mL of hexanes was added. The volatiles were removed under
reduced pressure prior to dissolving in 10 mL of dichloro-
methane and filtering. Once the dichloromethane was removed
under reduced pressure, the product was purified by column
chromatography.
Phenyl(piperidin-1-yl)methanone (Table 2, entry 5)
Purified by column chromatography (8 : 1 petroleum ether : ethyl
acetate) yielding 0.141 g (74%). Spectral data matched literature
references.22
N-Methyl-N-phenylbenzamide (Table 2, entry 6)
Purified by column chromatography (8 : 1 petroleum ether : ethyl
acetate) yielding 0.161 g (83%). Spectral data matched literature
references.60
Tishchenko reaction with 1
Inside a nitrogen filled glovebox, a 20 mL vial was charged with
1 (0.05 mmol), 2.5 mL toluene, benzaldehyde (2.00 mmol), and
a stir bar and the mixture was left to stir for 1 h before the vial
was removed from the glove box and 10 mL of hexanes was
added. The volatiles were removed under reduced pressure prior
to dissolving in 10 mL of dichloromethane and filtering. Once
the dichloromethane was removed under reduced pressure, the
product was purified by column chromatography (20 : 1 pet-
roleum ether : ethyl acetate) yielding 0.142 g (68%). Spectral
data matched literature references.58
N-Benzyl-N-methylbenzamide (Table 2, entry 7)
Purified by column chromatography (8 : 1 petroleum ether : ethyl
acetate) yielding 0.163 g (78%). Spectral data matched literature
references.61
N-Phenylpivalamide (Table 2, entry 8)
Purified by column chromatography (started with 1% ethyl
acetate in petroleum ether and very slowly increased to 5%)
yielding 0.036 g (21%). Spectral data matched literature
references.62
Qualitative monitoring of a typical amidation
Inside a nitrogen filled glovebox, a 20 mL vial was charged with
yttrium (amidate) complex (0.05 mmol), amine (1.00 mmol),
2.5 mL toluene, and a stir bar and the mixture was left stirring
for 30 min. Benzaldehyde (3.00 mmol) was added by syringe
and the mixture was left to stir. At set intervals (every 5 min) an
aliquot was removed and quenched with hexanes. For each
aliquot, the volatiles were removed and the sample diluted with
CDCl3 prior to obtaining a 1H NMR spectrum of each.
N-(4-Methoxyphenyl)-4-nitrobenzamide (Table 2, entry 9)
Purified by column chromatography (8 : 1 petroleum ether : ethyl
acetate) yielding 0.222 g (84%). Spectral data matched literature
references.63
N-p-Tolylbenzamide (Table 2, entry 1)
4-Nitro-N-p-tolylbenzamide (Table 2, entry 10)
Purified by column chromatography (8 : 1 petroleum ether : ethyl
acetate) yielding 0.151 g (74%). Spectral data matched literature
references.59
Purified by column chromatography (8 : 1 petroleum ether : ethyl
acetate) yielding 0.220 g (87%). Spectral data matched literature
references.59
N-Phenylbenzamide (Table 2, entry 2)
(4-Nitrophenyl)(piperidin-1-yl)methanone (Table 2, entry 11)
Purified by column chromatography (8 : 1 petroleum ether : ethyl
acetate) yielding 0.124 g (64%). Spectral data matched literature
references.22
Purified by column chromatography (8 : 1 petroleum ether : ethyl
acetate) yielding 0.232 g (98%). Spectral data matched literature
references.63
This journal is © The Royal Society of Chemistry 2012
Dalton Trans., 2012, 41, 7897–7904 | 7903

View Article Online
28 C. Y. Cai, L. Li, F. Xu and Q. Shen, Chin. Sci. Bull., 2010, 55, 3641–
3643.
(4-Chlorophenyl)(piperidin-1-yl)methanone (Table 2, entry 12)
29 J. A. Bexrud, C. Y. Li and L. L. Schafer, Organometallics, 2007, 26,
6366–6372.
30 C. Y. Li, R. K. Thomson, B. Gillon, B. O. Patrick and L. L. Schafer,
Chem. Commun., 2003, 2462–2463.
Purified by column chromatography (8 : 1 petroleum ether : ethyl
acetate) yielding 0.193 g (85%). Spectral data matched literature
references.9
31 Z. Zhang and L. L. Schafer, Org. Lett., 2003, 5, 4733–4736.
32 R. O. Ayinla and L. L. Schafer, Dalton Trans., 2011, 40, 7769–7776.
33 R. O. Ayinla and L. L. Schafer, Inorg. Chim. Acta, 2006, 359, 3097–
3102.
(4-Methoxyphenyl)(piperidin-1-yl)methanone (Table 2, entry 13)
34 R. O. Ayinla, T. Gibson and L. L. Schafer, J. Organomet. Chem., 2011,
696, 50–60.
35 R. K. Thomson, J. A. Bexrud and L. L. Schafer, Organometallics, 2006,
25, 4069–4071.
Purified by column chromatography (8 : 1 petroleum ether : ethyl
acetate) yielding 0.061 g (27%). Spectral data matched literature
references.64
36 M. C. Wood, D. C. Leitch, C. S. Yeung, J. A. Kozak and L. L. Schafer,
Angew. Chem., Int. Ed., 2007, 46, 354–358.
37 A. L. Reznichenko and K. C. Hultzsch, Organometallics, 2010, 29, 24–27.
38 G. F. Zi, J. Organomet. Chem., 2011, 696, 68–75.
39 Q. W. Wang, F. R. Zhang, H. B. Song and G. F. Zi, J. Organomet. Chem.,
2011, 696, 2186–2192.
Cyclohexyl(piperidin-1-yl)methanone (Table 2, entry 14)
Purified by column chromatography (started with 15% ethyl
acetate in petroleum ether and slowly increased to 30%) yielding
0.166 g (84%). Spectral data matched literature references.65
40 F. R. Zhang, H. B. Song and G. F. Zi, Dalton Trans., 2011, 40, 1547–
1566.
41 A. L. Gott, A. J. Clarke, G. J. Clarkson and P. Scott, Organometallics,
2007, 26, 1729–1737.
42 P. Eisenberger, R. O. Ayinla, J. M. P. Lauzon and L. L. Schafer, Angew.
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43 P. Eisenberger and L. L. Schafer, Pure Appl. Chem., 2010, 82, 1503–
1515.
44 J. A. Bexrud, P. Eisenberger, D. C. Leitch, P. R. Payne and L. L. Schafer,
J. Am. Chem. Soc., 2009, 131, 2116–2118.
Acknowledgements
The authors thank UBC, NSERC, and Nova Chemicals for
financial support of this work.
45 G. F. Zi, F. R. Zhang and H. B. Song, Chem. Commun., 2010, 46, 6296–
6298.
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7904 | Dalton Trans., 2012, 41, 7897–7904
This journal is © The Royal Society of Chemistry 2012