Development and mechanistic investigation of a highly efficient iridium(V) silyl complex for the reduction of tertiary amides to amines

Article abstract of DOI:10.1021/ja209567m

The cationic Ir(III) acetone complex (POCOP)Ir(H)₂(acetone) ⁺ (POCOP = 2,6-bis(di-tert-butylphosphinito)phenyl) was shown to catalyze the reduction of a variety of tertiary amides to amines using diethylsilane as reductant. Mechanistic studies established that a minor species generated in the reaction, the neutral silyl trihydride Ir(V) complex (POCOP)IrH₃(SiEt₂H), was the catalytically active species. High concentrations of this species could be conveniently generated by treatment of readily available (POCOP)IrHCl with tert-butoxide in the presence of Et₂SiH₂ under H₂. Thus, using this mixture in the presence of a trialkylammonium salt, a wide array of tertiary amides, including extremely bulky substrates, are rapidly and quantitatively reduced to tertiary amines under mild conditions with low catalyst loading. A detailed mechanistic study has been carried out and intermediates identified. In brief, (POCOP)IrH₃(SiEt₂H) reduces the amide to the hemiaminal silyl ether that, in the presence of a trialkylammonium salt, is ionized to the iminium ion, which is then reduced to the tertiary amine by Et ₂SiH₂. Good functional group compatibility is demonstrated, and a high catalyst stability has provided turnover numbers as high as 10 000.

Full text of DOI:10.1021/ja209567m

ARTICLE
pubs.acs.org/JACS
Development and Mechanistic Investigation of a Highly Efficient
Iridium(V) Silyl Complex for the Reduction of Tertiary Amides
to Amines
Sehoon Park and Maurice Brookhart*
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290, United States
S Supporting Information
b
ABSTRACT:
The cationic Ir(III) acetone complex (POCOP)Ir(H)2(acetone)+ (POCOP = 2,6-bis(di-tert-butylphosphinito)phenyl) was shown
to catalyze the reduction of a variety of tertiary amides to amines using diethylsilane as reductant. Mechanistic studies established
that a minor species generated in the reaction, the neutral silyl trihydride Ir(V) complex (POCOP)IrH3(SiEt2H), was the
catalytically active species. High concentrations of this species could be conveniently generated by treatment of readily available
(POCOP)IrHCl with tert-butoxide in the presence of Et2SiH2 under H2. Thus, using this mixture in the presence of a
trialkylammonium salt, a wide array of tertiary amides, including extremely bulky substrates, are rapidly and quantitatively reduced
to tertiary amines under mild conditions with low catalyst loading. A detailed mechanistic study has been carried out and
intermediates identified. In brief, (POCOP)IrH3(SiEt2H) reduces the amide to the hemiaminal silyl ether that, in the presence of a
trialkylammonium salt, is ionized to the iminium ion, which is then reduced to the tertiary amine by Et2SiH2. Good functional group
compatibility is demonstrated, and a high catalyst stability has provided turnover numbers as high as 10 000.
’ INTRODUCTION
epoxide functionalities was demonstrated. In a series of papers,
Nagashima and co-workers reported the reduction of both secondary
and tertiary amides to amines using various silanes and the ruthe-
nium cluster complex (μ3,η2:η3:η5-acenaphthylene)Ru3(CO)7 as a
catalyst.4e,f Using PhMe2SiH as the silane, this system selectively
reduces amides in the presence of ketone or ester functionalities.4g
The Nagashima group also demonstrated that using the bifunctional
silane 1,1,3,3-tetramethyldisiloxane (TMDS) Pt(IV) salts served as
efficient catalysts for reduction of tertiary amides to amines in good
to excellent yields.4o
Iron carbonyl complexes (Fe2(CO)9 or Fe3(CO)12) wereshown
to be efficient catalysts for reduction of amides by both Beller and
Nagashima.4l,m A convenient procedure developed by Beller in-
volved the use of polymethylhydrosiloxane (PMHS; 4ꢀ8 equiv)
and 2ꢀ10 mol % Fe2(CO9) in toluene or dibutyl ether at 100 °C
over 24 h. Generally good functional group tolerance was observed,
and yields were good to excellent. In a further recent advance, Beller
reported that Zn(OAc)2 was an effective catalyst at 10 mol %
loading for the reduction of tertiary amides with (EtO)3SiH under
Reduction of readily available tertiary amides is an attractive
route to tertiary amines, an important class of compounds which
exhibit a broad range of applications.1 Alkali-metal hydrides and
borohydrides are common reagents which can be used for such
reductions but suffer from several disadvantages, including poor
functional group tolerance, moisture and air sensitivity, and often
inconvenient methods required for product isolation and
purification.2 Catalytic hydrogenation of primary and secondary
amides to amines has been reported under conditions of high
pressures and temperatures, but reductions of tertiary amides via
hydrogenation have not been observed.3 Over the past few years,
metal-catalyzed reductions of amides employing silanes have
been extensively investigated, since silanes are easily handled and
environmentally attractive and product isolation procedures can
be convenient.4 These studies have resulted in the discovery of a
variety of catalytic systems with varying levels of scope, efficiency,
and functional group compatibility.4b,g,n,o In an early report Ito
and co-workers showed that the rhodium complex [RhH(CO)-
(PPh3)3] initiated the reduction of a variety of tertiary amides
with Ph2SiH2 at room temperature to afford the corresponding
tertiary amines in good to excellent yields.4b Tolerance of ester and
Received: October 11, 2011
Published: November 17, 2011
r
2011 American Chemical Society
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mild conditions in good to excellent yields.4n Good functional group
tolerance was noted.
’ RESULTS AND DISCUSSION
Reduction of Tertiary Amides with Et2SiH2 Catalyzed by
Iridium Complex 1. Complex 1 (0.5 mol %) together with either
Me2EtSiH or Et2SiH2 (3 equiv) initiates catalytic reduction of a
variety of tertiary amides, including aromatic, aliphatic, hetero-
aromatic, and heterocyclic amides, to produce the corresponding
tertiary amines in excellent yields at 60 °C (eq 5). The bulkier
silane triethylsilane, however, is nearly unreactive with tertiary
amides under similar conditions. The siloxanes Me2EtSiO-
SiEtMe2 and HEt2SiOSiEt2H are formed as the reactions pro-
ceed, as confirmed by 29Si{1H} NMR spectroscopy.
While a number of viable transition-metal catalysts have been
discovered for silane reductions of amides, mechanistic details
concerning these transformations are lacking.4e,l,n It is generally
assumed that the silane is “activated” by the metal complex via
oxidative addition to produce a metal silyl complex capable of
transferring R3Si+ to the carbonyl functionality to produce the
silyl-substituted oxocarbenium ion. This species then under-
goes hydride reduction to produce the silyl-substituted am-
inal. Amine is produced by ionization to the iminium ion
followed by a second hydride reduction (Scheme 1). No
intermediates in this cycle have been observed in the case of
transition-metal-based systems. Beller has observed an adduct
between Zn(OAc)2 and (EtO)3SiH which is presumed to
transfer (EtO)3Si+ to the amide to form an intermediate of
type A, which is then reduced by the remaining zinc hydride to
form an intermediate of type B.4n
Hemiaminal ethers resulting from a single hydrosilylation
event (first hydrosilylation) with Et2SiH2 are obtained in some
cases. Chlorobenzene is generally used as solvent; CDCl3 can be
employed as cosolvent for less soluble amides.
Recently we reported hydrosilylation of ketones (eq 1),5a
aldehydes (eq 1),5a esters (eq 1),5a and epoxides (eq 4)5c as well
as reduction of alkyl halides (eq 2)5d,f and ethers (eq 3)5b using
the highly electrophilic η1-silane complex 25e generated in situ
from the conveniently prepared acetone complex 1 in combina-
tion with Et3SiH (Scheme 2).
Results of typical reactions are illustrated in Table 1. Entry 1
shows that N,N-dimethylisobutylamide is reduced efficiently
with Et2SiH2 to attain 94% conversion in 1.5 h, while reduction
with Me2EtSiH proceeds more slowly (66% conversion in 22 h;
entry 2). With N,N-dimethylbenzamide as substrate, Me2EtSiH
exhibits a slow rate of conversion of the amide to the amine
(entry 3) similar to that in entry 2; however, Et2SiH2 leads to
more rapid reduction under similar conditions (entry 4). A low
catalyst loading of 0.1 mol % requires 6 h for complete conver-
sion of the amide to the amine (entry 5). Reduction of N,N-
diisopropylbenzamide, a very bulky tertiary amide, was examined
using Me2EtSiH or Et2SiH2. As expected, reduction of the amide
with Me2EtSiH gives only 3% conversion in 19 h (entry 6), but
using Et2SiH2 enables an efficient reduction of even this bulky
amide to give N,N-diisopropylbenzylamine (82% conversion in
54 h, entry 7). N,N-diphenylacetamide is quantitatively reduced
to N,N-diphenylethylamine with Et2SiH2 in 2 h (entry 8), while
N,N-diphenylbenzamide converts to N,N-diphenylbenzylamine
and N,N-diphenylsilylamine in a ratio of 3.5:1 in 4 h (entry 9).
Observation of N,N-diphenylsilylamine and toluene in the reac-
tion mixture indicates the further reduction of N,N-diphenyl-
benzylamine with the silane.
Results of the reactions of 1-acylpiperidine derivatives are
shown in entries 10ꢀ12. Rapid reduction of 1-formylpiperidine
with Et2SiH2 occurs at 23 °C. Although 1-benzoylpiperidine is
reduced with Et2SiH2 to the corresponding amine as usual, the
trifluoroacetyl-substituted amide exhibits a complex mixture of
products suggestive of both hydrosilylation of the carbonyl
functionality and CꢀF bond activation. In contrast, Me2EtSiH
exhibits a clean single hydrosilylation of the amide even with
excess Me2EtSiH to form only the corresponding hemiaminal
ether. Such a preference for a single hydrosilylation is also
observed in the hydrosilylation of ethyl trifluoroacetate with
Me2EtSiH catalyzed by 1.5a Results of catalytic reductions of γ-
and δ-lactams are shown in entries 13 and 14. Reduction of
1-methyl-2-pyrrolidinone with Et2SiH2 at 23 °C attains 91%
conversion in 27 h (reduction at 60 °C generates side products).
For a similar reason (avoidance of side products) the relatively
less reactive Me2EtSiH is preferred to Et2SiH2 for reduction of
1-benzyl-2-piperidinone, a δ-lactam, to the amine (entry 14, 20 h,
quantitative conversion).
In this paper we report applying complex 1 in combination
with diethylsilane for the reduction of tertiary amides to tertiary
amines. An in-depth mechanistic investigation provided sur-
prising details of this reduction process, which contrast
sharply with mechanistic processes determined for reactions
described in Scheme 2. A neutral Ir(V) catalyst resting state
has been identified together with characterization of inter-
mediates during the reduction process. On the basis of these
studies a highly efficient catalyst system has been developed
which exhibits broad scope, high yields, and high turnover
numbers (up to 10 000) under mild conditions, with signifi-
cant functional group tolerance.
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Scheme 1. General Mechanism of Metal-Catalyzed Reduction of Tertiary Amide with Hydrosilane
Scheme 2. Reduction of Carbonyl and Ether Compounds with a Cationic η1-Silane Iridium(III) Complex
Results of reductions of several N,N-dibenzylamide derivatives are
shown in entries 15ꢀ19. All conversions are essentially quantitative,
but in the case of N,N-dibenzylbenzamide 7% of the hemiaminal
ether is observed as well as 93% of the expected tribenzylamine.
CDCl3 as cosolvent in addition to chlorobenzene is needed for the
reduction of the naphthoylamide, due to its poor solubility in
chlorobenzene. Under these conditions, 96% conversion to the
amine is achieved in 27 h. The amides bearing cyclopropyl and
furanyl groups are conveniently and quantitatively reduced to the
corresponding amines with no formation of side products (entries 18
and 19). The azo group on the amide is well tolerated; reduction
affords only the desired amine product (entry 20).
their formation must result in production of 1 equiv of the conjugate
acid of the amide and/or the product amine. (NMR spectroscopic
data for intermediates are summarized in the Experimental Section.)
The minor species, complex 4, is considered to be formed via
reaction of 3 with a small amount of H2 which evolves from
hydrolysis of Et2SiH2 by adventitious H2O (the facile addition of
H2 to the iridium center of 3 to form 4 is demonstrated below).
Mechanistic Studies. Identification of Resting States by in
Situ 31P and 1H NMR Spectroscopy. As data in Table 1 show,
the reduction with Et2SiH2 exhibits catalytic activity significantly
higher than that with Me2EtSiH. To probe the potential reason
for differing activities, we initially monitored both working
1
catalyst systems by in situ H and 31P NMR spectroscopy to
identify the catalyst resting state(s).
Following the catalytic reduction of N,N-dimethylbenzamide by
Me2EtSiH in the presence of 1 (0.5 mol %) (eq 6), the observable
iridium species are the cationic silane complex (20, 69%)5d and the
amine and/or amide complex (31%).6 In sharp contrast, carrying out
the same experiment using Et2SiH2 (eq 7) indicates that the neutral
iridium(III) silyl hydride complex (3, ca. 90%) and the neutral
iridium(V) silyl trihydride complex (4, ca. 10%) are the dominant
resting states throughout the reaction. Since these species are neutral,
Complexes 3 and 4 in a ratio of 0.85:0.15 were independently
prepared at 60 °C in a quantitative yield by reaction of the neutral
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Table 1. Reduction of Tertiary Amides with Silanes Catalyzed by 1a
a Reaction conditions: 0.5 mol % 1, solvent C6D5Cl, 3 equiv of Me2EtSiH or Et2SiH2, 60 °C. b Determined by 1H and 13C{1H} NMR. c 0.1 mol % 1. d The ratio
[PhCH2NPh2]:[HEt2SiNPh2]:[toluene] is ca. 3.5:1:1. e Reaction at 23 °C. f NMR yield 84%. g CDCI3 is added as cosolvent. h 0.5 mol % (POCOP)lrH2 used
instead of 1 in C6D6.
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Scheme 3. Possible Structures for Trihydride 4
Scheme 4. Generation of the Indium Silyl Hydride Com-
plexes 3 and 4
iridium hydrido chloro complex 6 with NaOtBu in the presence
of excess Et2SiH2. Complex 4 is again thought to be formed
through the reaction of 3 with H2, which evolves from the
reaction of the formed HOtBu with Et2SiH2 (eq 8).7
to the amine complex (eq 9). No remaining 2 could be detected.
The 31P spectrum of the mixture of 20, Me2EtSiH, and NEt3 with
a ratio of 1:100:134 contains four resonances at δ 204.1, 190.4,
183.2, and 176.4, which are assignable to neutral dihydride 7
(28%), the neutral hydrido(silyl) iridium complex 3 (24%), the
silane complex 20 (40%), and the amine complex (5%), respec-
The 1H signal due to iridium hydride 3 appears at δ ꢀ16.9 as a
quartet (J = 6.0 Hz, equal coupling to both 31P nuclei and the
SiꢀH). This shift is very close to that for (POCOP)Ir(H)(SiEt3)
(30) at δ ꢀ15.9. Complex 4 exhibits a triplet at δ ꢀ8.8 (J = 10.5
Hz). This shift is close to that for iridium tetrahydride complex
(POCOP)IrH4 (5; δ ꢀ8.3)5b,d,8 The IrꢀH signal at δ ꢀ8.8 for 4
remains a sharp triplet at low temperatures (ꢀ70 °C), suggesting
that the three hydrides are rapidly interchanging even at ꢀ70 °C.
The 31P signals for complexes 3 and 4 occur at δ190.1 and 171.2,
respectively. The ratio (0.85:0.15) of 3 to 4 calculated on the
basis of relative intensities of proton signals due to iridium
hydrides is consistent with the ratio (0.86:0.14) based on the
31P NMR data when it is assumed that complex 4 is a trihydride,
thus supporting this structural assignment.
1
tively. On the basis of H and 31P NMR data, the equilibrium
constant Keq, relating 20 and the cationic amine complex, is
calculated to be ca. 0.1 (eq 10). It is noteworthy that Me2EtSiH
coordinates to the iridium center more strongly than does
Et3SiH. Interestingly, the acetone complex 1 when treated with
Et2SiH2 (600 equiv) and NEt3 (5 equiv) quantitatively converts
to 3 and 4 in a ratio of 0.67:0.33 in 10 min at 23 °C, as determined
by 31P NMR spectroscopy (eq 11). No cationic Ir species can be
observed.
It is well established that electrophilic iridium centers can
coordinate to silanes in an η2 fashion; therefore, an alternative to
the classical Ir(V) structure shown for 4 is an Ir(III) structure
(Scheme 3), in which the silane is bound in an η2 mode.
Normally this binding mode is identified by measuring the
29
1Hꢀ Si coupling constant, which falls in the range 20ꢀ200
Hz.9 The low natural abundance of 29Si (4.7%) often renders
these satellites difficult to detect. In the present case the rapid
scrambling of the three hydrides will reduce the observable J
1
29
value by one-third and thus the expected apparent Hꢀ Si
coupling will fall in the range 7ꢀ67 Hz.9e,f,i,j We have not been
able to detect a satellite consistent with this range, but the fact
that the hydride signal is a triplet and the lines are somewhat
broad (coupled with the low natural abundance of 29Si) does not
lead to full confidence in the assignment of 4 as a classical Ir(V)
trihydride, but that is the structure we currently favor.10
To probe the variation of catalyst resting states as a function of
the silane, we examined the reactions of various (POCOP)Ir(H)-
(silane)+ (silane = HSiEt3, HSiMe2Et, H2SiEt2) complexes with
NEt3 as a model base for the amide and amine product. The
31P{1H} NMR spectrum of the reaction mixture of the cationic
triethylsilane complex 2 and NEt3 (7 equiv) in the presence of
excess Et3SiH (256 equiv) exhibits a single signal at δ 175.1 due
The prompt conversion of 1 to monohydride 3 and trihydride
4 in the presence of Et2SiH2 by Et3N suggests that the silane
complex (Ir)(H)(H2SiEt2)+ (200), produced in situ from 1 and
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Scheme 5. Reduction of N,N-Dimethyl Benzamide with Different Loadings of Ir Catalyst, Et2SiH2, and Et3NH+
Et2SiH2, readily undergoes a deprotonation reaction with NEt3,
giving 3 and the corresponding ammonium borate salt [Et3NH]-
[B(C6F5)4].11 Subsequently, 3 can react with H2 (evolved from
the metal-catalyzed reduction of H2O with Et2SiH2) to form 4
(see Scheme 4).
Role of the Neutral Silyl Iridium Catalysts Monohydride 3
and Trihydride 4. To test the viability of 3 and 4 for initiating
catalysis, N,N-dimethylbenzamide was treated with Et2SiH2 at
60 °C in the presence of 1 mol % 3 and 4 (0.9:0.1 ratio). Over the
course of 1 h, the amide is quantitatively converted to the
hemiaminal ether B, the first hydrosilylation product, and a trace
of fully reduced N,N-dimethylbenzylamine. Extending the reac-
tion time to 3 h results in little further conversion to the amine.
This result is in sharp contrast to that when 1 initiates reduction
of the amide under similar conditions where a single product, N,
N-dimethylbenzylamine, is formed in 1 h. When complex 1
initiates catalysis, the neutral silane complexes 3 and 4 are formed
together with 1 equiv of the conjugate acid of the amide (or
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Scheme 6. Functional Group Tolerance on Reduction on N,N-Dimethylbenzamide Catalyzed by 3 and 4 with the Ammonium
Borate Salt
amine as reduction proceeds); therefore, we conclude that the pre-
sence of this conjugate acid is responsible for conversion of B to the
amine. To verify this conjecture, we treated the solution of hemi-
aminal B formed from reduction of N,N-dimethylbenzamide
(eq 12a) with 1 mol % Et3NH+ salt and observed that amine is
quantitatively formed in less than 5 min (eq 12b). These experi-
ments provide strong evidence that the catalytic reduction of amides
to amines in these systems takes place in two steps. First the
hydrosilylation of the amide to B occurs (experiments cited below
indicate that the Ir(V) species is the silane complex responsible for
this hydrosilylation), followed then by conversion of this ether to the
amine catalyzed by the conjugate acid of the amide/amine. A likely
intermediate in this second step is the iminium ion formed by acid-
catalyzed cleavage of the CꢀO bond of B.
sample of hemiaminal B (92%, contaminated with 8% dimethyl-
benzylamine) in toluene can be prepared by reacting the amide
with 3 equiv of Et2SiH2 and a mixture of the iridium silane catalysts
3 + 4 (0.6 mol %) at 60 °C. Using this in situ generated hemi-
aminal, the secondstep can be probed. Treating halfofthis mixture
with 0.1 mol % Et3NH+ salt at 23 °C results in conversion of only
ca. 2% of the ether to product amine after 27 min (eq 13a), while
treatmentofthe otherhalf with 1.0% Et3NH+ salt results in ca. 54%
conversion of ether to product after 24 min (eq 13b). Similarly,
using 2.5 mol % 3 + 4 and 1.3 equiv of Et2SiH2, a 94:6 mixture of B
and N,N-dimethylbenzylamine was prepared in toluene and the
solution divided in half. Treatment of one half with 1.0 mol %
Et3NH+ and 7.5 equiv of Et2SiH2 provided the amine in quanti-
tative yieldafter 9 min(eq14a). Incontrast, treatmentwith1.0 mol
% Et3NH+ and 0.8 equiv of Et2SiH2 converted only 36% of the
ether to the tertiary amine after 16 min (eq 14b). The results
summarized in eqs 15a and 15b indicate the rate of conversion of B
to the amine is independent of concentration of iridium catalyst.
The qualitative results in eqs 13ꢀ15 imply that the rate of
conversion of the hemiaminal ether B is dependent on ammonium
ion concentration (acid) and Et2SiH2 concentration, indicating
that the silane, not the iridium hydride, is the hydride donor in this
transformation. A mechanism consistent with these data involves
the acid-induced reversible formation of the iminium ion C,
followed by Et2SiH2 attack on the iminium ion as summarized in
eq 16. Of course, when catalysis is carried out in the presence of
To further probe this second step, reduction of the hemi-
aminal ether, we have carried out experiments summarized in
Scheme 5 employing N,N-dimethylbenzamide. A nearly pure
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acid, the formation of the hemiaminal is turnover limiting and its
subsequent conversion to amine is rapid.
Figure 1. 31P{1H} NMR spectra of a mixture of monohydride 3 and
trihydride 4 in C6D6 at 23 °C (a), under an H2 atmosphere (b), followed
by purging with argon (c).
Functional Group Tolerance of the Catalyst System
Composed of Monohydride 3, Trihydride 4, and Et3NH+.
Once the mixture of 3 and 4 together with [Et3NH]-
[B(C6F5)4] was found to be effective for the reduction of
amides, we employed this catalyst system for reduction of N,
N-dimethylbenzamide in the presence of various function-
alized molecules to investigate the functional group toler-
ance and chemoselectivity of the reaction (Scheme 6). The
reduction of the amide with Et2SiH2 proceeds smoothly in
the presence of stoichiometric amounts of 1-hexene, 3-hex-
yne, tetrahydrofuran, and acetonitrile without any signifi-
cant effect on the rate of the conversion or yield (quantita-
tive conversion in 1.5 h at 60 °C). Acetonitrile, 1-hexene,
3-hexyne, and tetrahydrofuran are unreactive under these
conditions, indicating excellent chemoselectivity with re-
spect to these functional groups. The presence of octyl
bromide appears to slightly retard the rate of reduction,
but virtually all of the bromide remains following reduction. Under
the reaction conditions, ketone and ester are hydrosilylated in
competition with amide reduction. In the presence of 1 molar
equiv of acetone or ethyl propionate, dimethylbenzamide is
reduced at ca. 2 and 4 times the rate, respectively, at which
acetone and ethyl propionate are hydrosilylated.
among 3, H2, and 4 had been established (enhancement of 3 with
time could be due in part to loss of H2 from solution).
Exposure of a C6D6 solution of 3and 4(9:1) (Figure1a) to1atm
of H2 at 23 °C in the presence of Et2SiH2 results in the rapid
conversion of 3 to 4 to reach a ratio of 2:3 after 10 min (Figure 1b).
Subsequently, purging this solution with argon leads to conversion
of 4 back to 3 and, after 5 min, the ratio is ca. 9:1 (Figure 1c). These
results clearly indicate that the formation of 4 from 3 is proportional
to the concentration of H2 and that 3and H2 are in rapid equilibrium
with 4 at 23 °C through addition and elimination of dihydrogen to
the Ir center (eqs 19 and 20).
Equilibrium among 3, 4, and 7 during Catalysis. Recently
we reported that the dihydride complex 7 reacts rapidly with
Et3SiH to generate an equilibrium mixture of 7 and the neutral
iridium silyl hydride complex 30 at 23 °C. Under 1 atm of H2,
equilibrium is established in ca. 1 h and results in a ca. 0.8:1 ratio
of 30 to 7 (eq 17).5b These results prompted examination of the
reaction of 7 with Et2SiH2 in order to explore the equilibration of
3, 4, and 7 and the role these equilibria may play in catalysis.
To gain further insights into the resting states (3 and 4)
observed during catalysis, we carried out several reactions of 3, 4,
and 7 with Et2SiH2, H2, and D2 at 23 °C. Addition of Et2SiH2 (10
equiv) to a solution of 7 in C6D6 results in complete conversion
to a mixture of 3 and 4 (0.71:0.29 ratio) in 10 min at 23 °C on the
basis of 31P{1H} NMR (eq 18a).12 After 3 h only a small change in
the ratio to 0.84:0.16 occurred (eq 18b), suggesting equilibrium
Reaction of the mixture of 3 and 4 (9:1) with D2 (1 atm) in the
presence of Et2SiH2 (20 equiv) at 23 °C affords a mixture of 3 and 4
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Scheme 7. Induction of Formation of 7 and 5 from a Mixture of 3 and 4
in a ratio of 0.34:0.66 in 0.5 h (eq 19). Furthermore, the 2H NMR
spectrum of the solution shows that deuterium has been incorpo-
rated intothe free silane. Judgingfrom the intensity of the2H signal
atδ 3.84relativeto aninternalstandard (toluene-d8) ca. 3ꢀ7 equiv
of deuterium (relative to Ir) was exchanged into the silane. This
result strongly suggests facile reversible reductive elimination of
Et2SiH2 from complex 4 via formation of 7 (eq 20).
To further probe loss of Et2SiH2 from 4, two additional experi-
ments were carried out, as summarized in Scheme 7. A 4:6 ratio of 3
to 4 was generated in toluene-d8 under 1 atm of H2. Purging of this
solution with H2 at 23 °C over a period of time (0.3 h) resulted in
flushing all Et2SiH2 from the solution and eventual conversion of
both 3 and 4 to tetrahydride 5, no doubt through loss of silane from
4 to form the dihydride 7, followed by reaction with H2 (path A).8 A
second experiment was carried out, in which the mixture of 3 and 4
was subjected to high vacuum. In this case, 3 was the dominant
product with traces of dihydride 7, indicating that H2 loss from 4 is
more rapid than loss of silane (path B).
Catalytic Reduction of Tertiary Amides with Et2SiH2 under 1
atm H2. Although 3 is the major catalyst resting state under the
catalytic conditions investigated above, it seems likely that the minor
iridium species present, Ir(V) complex 4, is a much more active
Et2SiH+ donor and thus the active catalyst in the first step (and the
turnover-limiting step of the reduction), the hydrosilylation of the
amide. Since 3 and 4 are in rapid equilibrium and the concentration
of 4 can be increased under hydrogen, we have investigated the
catalysis under an atmosphere of hydrogen. The general conditions
we have used are summarized in eq 21. Indeed, carrying out the
reaction under hydrogen substantially accelerates the reductions and
supports the contention that 4 is the active catalyst.
to qualitatively assess differences in rates of reduction.
Reduction of N,N-dimethylisobutylamide under H2 (1 atm)
is complete in only 0.4 h but gives not only the desired amine
product (81%) but also a side product, N,N,2-trimethylprop-
1-en-1-amine (19%) (entry 1). Entry 2 shows that N,N-
dimethylbenzamide can be quantitatively reduced using 1
mol % Ir loading at 23 °C to give the corresponding amine
quantitatively in only 0.3 h. This compares with the reduction
in Table 1 using 0.5% catalyst loading at 60 °C, which
required 1 h for quantitative reduction. A low catalyst load-
ing of only 0.01 mol % in combination with 0.3 mol % of
[Et3NH][B(C6F5)4] initiates reduction at 60 °C to attain a
quantitative conversion in 4 h with formation of the hemiaminal
ether and N,N-dimethylbenzylamine in a 0.12:0.88 ratio. Pro-
longed reaction at 60 °C for 11 h provides conversion of the
hemiaminal ether to dimethylbenzylamine as a final product in
98% yield (entry 3). It is noteworthy that ca. 10 000 turnovers
have been achieved in 11 h under mild conditions (60 °C, 3 equiv
of Et2SiH2, H2 (1 atm)). N,N-Diisopropylbenzamide, containing
very bulky i-Pr substituents, undergoes facile reduction under H2,
giving diisopropylbenzylamine in quantitative yield in 2.5 h
(entry 4). This rate under a H2 atmosphere sharply contrasts
with that observed in the reduction catalyzed by 1 (82%
conversion in 54 h at 60 °C). In addition, the efficiency of
reduction of this hindered substrate contrasts favorably with that
observed in its iron carbonyl catalyzed reduction (59% yield in 24 h at
100 °C).4l Reduction of N,N-diphenylacetamide is slower
than that of N,N-dimethylbenzamide under the same condi-
tions but still faster than that in the catalyst system composed
of 1 and Et2SiH2 (entry 5). Similar to the case for N,N-
dimethylbenzamide, N,N-dibenzylamide derivatives contain-
ing benzyl or phenyl substituents on the carbonyl carbon are
easily reduced to produce the amines quantitatively in 0.4 h
(entries 6 and 7). The amide derivatives containing cyclo-
propyl and 1-furanyl groups were tested for reduction under
H2. These substrates yield the amine in 0.2 h in quantitative
yields (entries 8 and 9). 1-Benzoylpiperidine is also quantita-
tively reduced to 1-benzylpiperidine in 0.1 h with Et2SiH2
under H2 (entry 10). N,N-Dibenzylamide having a 1-naphthyl
group on the α-carbon converts to the corresponding amine
Table 2 summarizes results of catalysis under H2. These
data can be compared to data in Table 1 (argon atmosphere)
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Table 2. Reduction of Tertiary Amides with Et2SiH2 Catalyzed by a Mixture of 3 and 4 with Ammonium Borate Salt, Et3NH
B(C6F5)4, under H2 (1 atm)a
a Reaction conditions: 1 mol % 3 + 4 and 1 mol % [Et3NH][B(C6H5)4], 1 atm of H2, solvent C6D6, 3 equiv of Et2SiH2, 60 °C. b Determined by 1H
and 13C{1H} NMR. c Gas evolution observed during the reaction. d Reaction at 23 °C. e 0.01 mol % catalyst (3 + 4) in combination with 0.3 mol %
f
g
[Et3NH][B(C6H5)4]. In a preparation-scale run (1 g), tribenzylamine was isolated as a crystalline product in 90% yield. CDCl3 is added as
cosolvent.
to attain 95% conversion in 15 h under a H2 atmosphere (entry
1 (Table 1, entry 17) or employing Fe3(CO)124l with PMHS
11), which is more efficient than reduction employing catalyst
as reductant.
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Scheme 8. Proposed Catalytic Cycle for the Reduction of Tertiary Amides
’ SUMMARY
Catalyst loadings as low as 0.01% have provided quantitative
reductions (10 000 turnovers). The catalyst system is com-
patible with a range of functional groups, including alkenes,
internal alkynes, ethers, nitriles, and halides. Primary and sec-
ondary amines are not successfully reduced with this catalyst
system.
Scheme 8 summarizes the proposed catalytic cycle for reduc-
tion of tertiary amides on the basis of the mechanistic results
described above. The active silylating agent is the Ir(V) trihy-
dride complex 4. This complex is generated in situ from the
cationic acetone complex 1 (see Scheme 4) or, more conveni-
ently, from treatment of (POCOP)IrHCl with tert-butoxide in
the presence of Et2SiH2 (see eq 8). The concentration of 4 is
increased under a hydrogen atmosphere by shifting the equilib-
rium from Ir(III) silyl hydride 3 toward silyl trihydride 4, as
shown in Scheme 8 (see also eq 20). Thus, catalysis is signifi-
’ EXPERIMENTAL SECTION
General Considerations. All manipulations were carried out
using standard Schlenk, high-vacuum, and glovebox techniques. Argon
and nitrogen were purified by passing through columns of BASF R3-11
catalyst (Chemalog) and 4 Å molecular sieves. THF was distilled under a
nitrogen atmosphere from sodium benzophenone ketyl prior to use.
Methylene chloride and toluene were passed through columns of
activated alumina13 and degassed either by freezeꢀpumpꢀthaw meth-
ods or by purging with argon. Benzene, acetone, and acetonitrile were
dried with 4 Å molecular sieves and degassed by freezeꢀpumpꢀthaw
methods. Et3SiH, Me2EtSiH, and Et2SiH2 were dried with LiAlH4 and
vacuum-transferred into a sealed flask. Unless otherwise stated, all of the
other substrates for the preparation of amides were purchased from
Sigma-Aldrich and were used without purification. Deuterated solvents
(CD2Cl2, C6D5CD3, C6D5Cl, C6D6) and pentane were dried with CaH2
or 4 Å molecular sieves and vacuum-transferred into a sealed flask. NMR
spectra were recorded on Bruker spectrometers (DRX-400, AVANCE-
400, AMX-300, and DRX-500). 1H and 13C NMR spectra were referenced
to residual protio solvent peaks. 29Si chemical shifts were referenced
to external Et3SiH. Ph3C[B(C6F5)4],14 (POCOP)Ir(H)2 (7),8 and
[(POCOP)Ir(H)(acetone)]+[B(C6F5)4]ꢀ (1)5d were prepared ac-
cording to published procedures.
cantly accelerated under H2. Silyl complex 4 transfers Et2SiH+ to
the amide to yield the oxocarbenium ion A and (POCOP)IrH3
ꢀ
.
The oxocarbenium ion A is converted to the hemiaminal B by
reaction with (POCOP)IrH3ꢀ, which is converted to the dihy-
dride 7. The dihydride reenters the catalytic cycle by reaction
with Et2SiH2 to regenerate 4. The hemiaminal requires a weak
acid (in this case we show Et3NH+) for further reduction by
conversion to the iminium ion C, which is then reduced by
Et2SiH2 to yield the amine. The silanol produced from the
ionization of the hemiaminal reacts with the (formally) generated
Et2SiH+ and the tertiary amine to yield the siloxane and regen-
erate the ammonium salt Et3NH+.
As noted, the most effective and easily generated catalyst is
prepared by treatment of the (POCOP)IrHCl complex with tert-
butoxide in the presence of Et2SiH2 and hydrogen. This system is
a remarkably active and long-lived catalyst. Very highly hindered
amides can be reduced readily under mild conditions using low
catalyst loadings. For example, N,N-diisopropylbenzamide is quan-
titatively reduced in 2.5 h at 60 °C using 1 mol % catalyst loading.
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Scheme 9. Neutral Hydrido(silyl)liridium Pincer Complexes
Determination of the Equilibrium Constant, Keq, Relating
Cationic Iridium Silane Complex (2 or 20) and Cationic Iridium
Amine Complex (eqs 9 and 10).5d. The equilibrium constants were
determined by NMR spectroscopy. The concentration ratio of 20 to the
amine complex [(POCOP)Ir(H)(NEt3)]+[B(C6F5)4]ꢀ was determined
by 31P NMR, and the concentration ratio of Me2EtSiH to Et3N was
determined by 1H NMR. Keq was calculated to be ca. 0.1. The
equilibrium constant between 2 and the cationic iridium amine
complex was not obtainable by NMR spectroscopy, due to the very
low equilibrium concentration of 2.
General Procedure for the Preparation of Amides.4l. The
acyl chloride (15.0 mmol) was added in one portion to a solution of the
amine (16.5 mmol), Et3N (18.75 mmol), and CH2Cl2 (30 mL) at 23 °C
(eq 22). The reaction mixture was stirred for 1 h at 23 °C and then was
diluted with CH2Cl2 (45 mL). The solution was transferred to a
separatory funnel and was washed two times with 30 mL of 1 N HCl
and two times with 30 mL of saturated NaCl solution. The organic layer
was dried with Na2SO4, filtered, and concentrated under reduced
pressure. All the NMR data for the synthesized amides matched those
reported by Beller.4l
General Procedure for Reduction of N,N-Dimethylbenza-
mide Catalyzed by a Mixture of Monohydride 3 and Trihy-
dride 4 with Et2SiH2 in the Presence of [Et3NH][B(C6F5)4]. A
stock solution of complexes 3 and 4 (33 mM, ratio ca. 9:1) was prepared
in toluene-d8 in a glovebox. An aliquot (75 μL, 0.5 mol % Ir) of this stock
solution was then added to Et2SiH2 (1.5 mmol, 0.19 mL, 3.0 equiv) in
toluene-d8 (0.3 mL) in a medium-walled J. Young NMR tube. The
substrate (0.5 mmol, 75 mg, 1.0 equiv) was then added together with
[Et3NH][B(C6F5)4] (0.005 mmol, 3.9 mg, 1.0 mol %), and the reaction
mixture was heated to 60 °C for 1 h in an oil bath. The progress was
followed by 1H and 13C{1H} NMR spectroscopy. Conversion was
determined by monitoring the loss of N,N-dimethylbenzamide.
Reduction of N,N-Dimethylbenzamide with Et2SiH2 Using
Different Loadings of Catalyst (3 + 4), Followed by Addition
of [Et3NH][B(C6F5)4]. A stock solution of complexes 3 and 4
(100 mM, ratio ca. 9:1) was prepared in toluene-d8 in a glovebox.
Two aliquots (90 μL, 3.0 mol % Ir; 10 μL, 0.3 mol % Ir) of this stock
solution were then added to Et2SiH2 (0.9 mmol, 0.12 mL, 3.0 equiv) in
toluene-d8 (0.3 mL) in two medium-walled J. Young NMR tubes,
respectively. The substrate (0.3 mmol, 45 mg, 1.0 equiv) was then
added to the two NMR tubes, and the reaction mixtures were heated to
60 °C for 1ꢀ2 h in an oil bath. Following the hydrosilylation,
[Et3NH][B(C6F5)4] (0.004 mmol, 3.0 mg, 2.5 mol %) was added to
each NMR tube, and the two mixtures were allowed to react at 23 °C for
10 min. The progress was followed by 1H and 13C{1H} NMR
spectroscopy. Conversion was determined by monitoring the loss of
N,N-dimethylbenzamide.
Typical Competition Experiments To Determine Rela-
tive Reactivities of N,N-Dimethylbenzamide and 1-Hex-
ene, 3-Hexyne, THF, MeCN, Acetone, or Ethyl Propionate
by NMR. Et2SiH2 (1.5 mmol, 0.19 mL, 3.0 equiv) was added to a
solution of 3 and 4 (0.004 mmol, 0.8 mol %) in toluene-d8 (0.3 mL)
in a medium-walled J. Young NMR tube, and the contents were well
shaken. N,N-Dimethylbenzamide (75 mg, 0.5 mmol, 1.0 equiv) and
reactive compounds containing 1-hexene, 3-hexyne, THF, MeCN,
acetone, or ethyl propionate (0.5 mmol, 1.0 equiv) were then added
together with [Et3NH][B(C6F5)4] (0.005 mmol, 3.9 mg, 1.0 mol %)
and mesitylene (14 μL, 0.1 mmol, 25 equiv) as an internal standard.
The reaction mixture was heated to 60 °C for 1.5 h in an oil bath, and
the progress was followed by NMR spectroscopy.
For amides in entries 9 and 16 (Table 1): purified by recrystallization
from ethanol and methanol, respectively.
For amides in entries 11 and 18 (Table 1): purified via silica gel
column chromatography using ethyl acetate/hexane (1:10).
For amides in entries 15, 17, 19, and 20: purified by washing with
hexane several times after removing solvents.
General Procedure for the Reduction of Tertiary Amides
Catalyzed by Cationic Iridium Acetone Complex 1 with
Hydrosilanes. The hydrosilane (1.5 mmol, 3.0 equiv) was added to
a solution of 1 (3.3 mg, 0.0025 mmol, 0.5 mol %) in C6D5Cl (0.3 mL) in
a medium-walled J. Young NMR tube, and the contents were well
shaken. The substrate (0.5 mmol, 1.0 equiv) was then added, and this
mixture was allowed to stand at 23 °C or was heated to 60 °C in an oil
bath. The progress was followed by NMR spectroscopy. Conversions
were determined by monitoring the loss of tertiary amides. Amines as
reduction products were identified using 1H and 13C{1H} NMR dada in
comparison to literature data4l or authentic samples.
In Situ Generation of a Mixture of (POCOP)Ir(H)(SiEt2H) (3)
and (POCOP)Ir(H)3(SiEt2H) (4) from (POCOP)Ir(H)Cl and
NaOtBu in the Presence of Et2SiH2. Et2SiH2 (26 μL, 0.2 mmol,
10 equiv) in toluene-d8 (0.5 mL) was added to a mixture of
(POCOP)Ir(H)(Cl) (12.6 mg, 0.02 mmol, 1 equiv) and NaOtBu (2.4
mg, 0.024 mmol, 1.2 equiv) in a medium-walled J. Young NMR tube,
and this mixture was heated to 60 °C for 4 h, resulting in a mixture of 3
and 4 in a ratio of ca. 0.85:0.15. Labeling for 3 and 4 is given in Scheme 9.
Data for 3 are as follows. 1H NMR (toluene-d8, 400 MHz, 23 °C): δ 7.02
(t, 1H, b, 3JHꢀH = 7.6 Hz), 6.86 (d, 2H, a, 3JHꢀH = 7.6 Hz), 5.54 (br s,
1H, SiH), 1.39 (t, 36H, 4 ꢁ t-Bu), 1.30ꢀ1.33 (m, 10 H, SiEt, overlap
In Situ Generation of a Mixture of (POCOP)Ir(H)(SiEt2H) (3)
and (POCOP)Ir(H)3(SiEt2H) (4) from (POCOP)Ir(H)2 (7) and
Et2SiH2. Et2SiH2 (13 μL, 0.1 mmol, 10 equiv) in toluene-d8 (0.5 mL)
was added to (POCOP)Ir(H)2 (5.9 mg, 0.01 mmol, 1 equiv) in a
medium-walled J. Young NMR tube, and this mixture was allowed to
stand at 23 °C for 10 min, resulting in a mixture of 3 and 4 in a ratio of ca.
071:0.29 with H2 evolution.
In Situ Generation of a Mixture of 3 and 4 from 7 and
Et2SiH2, Followed by Exposure to H2. Et2SiH2 (13 μL, 0.1
mmol, 10 equiv) in toluene-d8 (0.5 mL) was added to 7 (5.9 mg, 0.01
mmol, 1 equiv) in a medium-walled J. Young NMR tube. Subsequently,
this mixture was allowed to stand at 23 °C for 10 min, followed
by degassing by freezeꢀpumpꢀthaw methods. H2 or D2 (1 atm)
was finally vacuum-transferred to the degassed J. Young NMR tube.
2
3
with tBu), ꢀ16.87 (q, 1H, IrꢀH, JPꢀH = 6.0 Hz, JHꢀSiH = 6.0 Hz).
13C{1H} NMR (toluene-d8, 100.6 MHz, 23 °C): δ 13.15 (SiEt2H),
11.98 (SiEt2H). 31P{1H} NMR (toluene-d8, 162 MHz, 23 °C): δ 190.3.
29Si{1H} DEPT 45 (toluene-d8, 79 MHz, 23 °C): δ ꢀ13.3. Data for 4
are as follows. 1H NMR (toluene-d8, 400 MHz, 23 °C): δ 6.90 (t, 1H, b0,
3JHꢀH = 7.5 Hz), 6.72 (d, 2H, a0, 3JHꢀH = 7.5 Hz), 5.40 (br s, 1H, SiH),
1.31 (t, 36H, 4 ꢁ tBu), 1.30ꢀ1.33 (m, 10 H, SiEt, overlap with tBu),
2
ꢀ8.90 (t, 3H, IrꢀH, JPꢀH = 10.5 Hz). 13C{1H} NMR (toluene-d8,
100.6 MHz, 23 °C): δ 14.03 (SiEt2H), 12.16 (SiEt2H). 31P{1H} NMR
(toluene-d8, 162 MHz, 23 °C): δ 171.4. 29Si{1H} DEPT 45 (toluene-d8,
79 MHz, 23 °C): δ ꢀ20.62.
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The change in the ratio of 3 to 4 was monitored by 1H and 31P{1H}
NMR spectroscopy.
4.74 (m, 1H), 2.31 (s, 6H); 13C{1H} NMR (C6D6, 100.6 MHz, 23 °C) δ
141.82, 127.6, 127.2, 126.9, 91.3, 38.8, 5.82, 5.37.
Data for N,N-diisopropylbenzylamine (entry 7): 1H NMR (C6D5Cl,
400 MHz, 23 °C) δ 7.50ꢀ7.28 (m, 5H, overlap with solvent peaks), 3.63
(s, 2H), 3.00 (septet, J = 6.5 Hz, 2H), 1.11 (d, 12H, overlap with excess
Et2SiH2); 13C{1H} NMR (C6D5Cl, 100.6 MHz, 23 °C) δ 139.81,
128.42, 128.22, 126.33, 49.05, 47.82, 20.72.
In Situ Generation of 5 from a Mixture of 3 and 4 (Method A).
Et2SiH2 (13 μL, 0.1 mmol, 10 equiv) in toluene-d8 (0.5 mL) was added to 7
(5.9 mg, 0.01 mmol, 1 equiv) in a medium-walled NMR tube with a screw
cap. Subsequently, this mixture was allowed to stand at 23 °C for 10 min,
followed by introducing H2 via brief H2 purging through the solution. The
solution was stirred for 1 h at 23 °C to give a mixture of 3 and 4 in a ratio of
ca. 0.4:0.6. This solution containing 3 and 4 was purged with H2 for 20 min
at 23 °C, during which time excess Et2SiH2 was removed, to afford mainly
the iridium tetrahydride complex 5 (ca. 94%).
In Situ Generation of 7 from a Mixture of Monohydride 3
and Trihydride 4 (Method B). Et2SiH2 (13 μL, 0.1 mmol, 10 equiv)
in toluene-d8 (0.5 mL) was added to 7 (5.9 mg, 0.01 mmol, 1 equiv) in a
medium-walled J. Young NMR tube. Subsequently, this mixture was
allowed to stand at 23 °C for 10 min, followed by degassing by
freezeꢀpumpꢀthaw methods. H2 (1 atm) was vacuum-transferred to
the degassed J. Young NMR tube. The solution was stirred for 1 h at
23 °C to give a mixture of 3 and 4 in a ratio of ca. 0.4:0.6. This solution
containing 3 and 4 was subjected to high vacuum, resulting in a mixture
of 7 and 3 in a ratio of 0.06:0.91.
General Procedure for the Reduction of Tertiary Amides
Catalyzed by a Mixture of Monohydride 3 and Trihydride 4
with Et2SiH2 in the Presence of [Et3NH][B(C6F5)4] under H2 (1
atm). Et2SiH2 (1.5 mmol, 0.19 mL, 3.0 equiv) was added to a solution of 3
and 4 (0.005 mmol, 1.0 mol %) in C6D6 (0.3 mL) in a medium-walled J.
Young NMR tube, and the contents were well shaken. The substrate (0.5
mmol, 1.0 equiv) was then added together with [Et3NH][B(C6F5)4]
(0.005 mmol, 3.9 mg, 1.0 mol %), followed by degassing by freezeꢀ
pumpꢀthaw methods. Finally, 1 atm of H2 was vacuum-transferred to the
degassed J. Young NMR tube. The reactions were then allowed to stand at
23 °C or heated to 60 °C in an oil bath. The reaction progress was followed
by NMR spectroscopy. Conversions were determined by monitoring the
loss of tertiary amides.
Data for N,N-diphenylethylamine (entry 8): 1H NMR (C6D5Cl, 400
MHz, 23 °C) δ 7.50ꢀ7.10 (m, 10H, overlap with solvent peaks), 3.84
(q, J = 6.8 Hz, 2H), 1.31 (t, 3H, overlap with excess Et2SiH2); 13C{1H}
NMR (C6D5Cl, 100.6 MHz, 23 °C) δ 147.87, 129.28, 121.14, 120.8,
46.27, 12.50.
Data for N,N-diphenylbenzylamine and N,N-diphenyldiethylsilyl-
1
amine (entry 9): H NMR (C6D5Cl, 400 MHz, 23 °C, selected data)
δ 5.06 (m, 1H), 4.93 (s, 2H); 13C{1H} NMR (C6D5Cl, 100.6 MHz,
23 °C, selected data) δ 56.33, 41.57.
Data for 1-methylpiperidine (entry 10): 1H NMR (C6D5Cl, 400
MHz, 23 °C) δ 2.41 (m, 4H), 2.32 (br s, 3H), 1.71 (m, 4H), 1.52
(br s, 2H); 13C{1H} NMR (C6D5Cl, 100.6 MHz, 23 °C) δ 56.61,
46.88, 26.23, 24.15.
Data for 1-benzylpiperidine (entry 11): 1H NMR (C6D5Cl, 400
MHz, 23 °C) δ 7.50ꢀ7.31 (m, 5H, overlap with solvent peaks), 3.56
(s, 2H), 2.50 (br s, 4H), 1.71 (m, 4H), 1.58 (br s, 2H); 13C{1H} NMR
(C6D5Cl, 100.6 MHz, 23 °C) δ 139.49, 129.26, 128.19, 126.71, 63.93,
54.66, 26.33, 24.74.
Data for 1-(1-(ethyldimethylsilyl)oxy)-2,2,2-trifluoroethyl)piperidine
(entry 12): 1H NMR (C6D5Cl, 400 MHz, 23 °C) δ 4.58 (q, J = 3.5 Hz,
1H), 2.89 (t, J = 5.2 Hz, 4H), 1.70ꢀ1.52 (m, 6H), 1.18 (m, O-SiMe2Et,
overlap with excess Me2EtSiH), 0.76 (m, O-SiMe2Et, overlap with excess
Me2EtSiH); 13C{1H} NMR (C6D5Cl, 100.6 MHz, 23 °C) δ 122.84 (q, J =
285.7 Hz, overlap with solvent peaks), 86.39 (q, J = 32.1 Hz), 48.74, 26.46,
24.79, 8.49, 6.57, ꢀ2.61 (tentative).
1
Data for 1-methylpyrrolidine (entry 13): H NMR (C6D5Cl, 400
MHz, 23 °C) δ 2.40 (br s, 4H), 2.31 (s, 3H), 1.71 (m, 4H); 13C{1H}
NMR (C6D5Cl, 100.6 MHz, 23 °C) δ 56.16, 41.86, 24.18.
General Procedure for a Large-Scale Reduction of N,N-
Dibenzylbenzamide. Et2SiH2 (10.0 mmol, 1.30 mL, 3.0 equiv) was
added to a solution of 3 and 4 (0.01 mmol, 0.2 mol %) in toluene-d8
(3.0 mL) in a 25 mL flame-dried Schlenk tube containing a stir bar. The
substrate (3.32 mmol, 1.0 g, 1.0 equiv) was then added together with
Et2OHB(C6F5)4 (0.032 mmol, 24 mg, 1.0 mol %), followed by purging
H2 (1 atm) through the stirred solution for 1 min. The reaction mixture
was then heated to 60 °C overnight in an oil bath. Completion of
1
Data for 1-benzylpiperidine (entry 14): H NMR (C6D5Cl, 400
MHz, 23 °C) δ 7.40ꢀ7.22 (m, 5H, overlap with solvent peaks), 3.44
(s, 2H), 2.36 (m, 4H), 1.60ꢀ1.47 (m, 6H; 13C{1H} NMR (C6D5Cl,
100.6 MHz, 23 °C) δ 139.45, 128.87, 128.13, 127.56, 63.85, 54.57,
26.25, 24.67.
Data for N,N-dibenzyl-3-phenylpropan-1-amine (entry 15): 1H
NMR (C6D5Cl, 400 MHz, 23 °C) δ 7.45ꢀ7.06 (m, 15H, overlap with
solvent peaks), 3.55 (s, 4H), 2.58 (t, J = 7.5 Hz, 2H), 2.49 (t, J = 7.0 Hz,
2H), 1.82 (t, J = 7.0 Hz, 2H); 13C{1H} NMR (C6D5Cl, 100.6 MHz,
23 °C) δ 142.44, 139.96, 128.85, 128.40, 128.21, 128.14, 126.82, 125.75,
58.51, 52.95, 33.57, 29.27.
1
the reaction was confirmed by H NMR spectroscopy. The volatiles
were removed under reduced pressure. The residue was dissolved in
pentane and washed three times with 10 mL of NaOH (1 M) solution.
The organic layer was concentrated in vacuo to give a crude product.
The crude product was purified by recrystallization from ethanol to yield
0.86 g of tribenzylamine as a white solid (90%).
1
Data for tribenzylamine (entry 16): H NMR (C6D5Cl, 400 MHz,
23 °C) δ 7.48ꢀ7.22 (m, 15H, overlap with solvent peaks), 3.55 (s, 6H);
13C{1H} NMR (C6D5Cl, 100.6 MHz, 23 °C) δ 139.67, 128.89, 128.21,
126.88, 58.04.
NMR Spectroscopic Data of Amine Products in Table 1.4l
Data for N,N-dimethylisobutylamine (entry 1): 1H NMR (C6D5Cl, 400
MHz, 23 °C) δ 2.30 (s, 6H), 2.11 (d, J = 7.6 Hz, 2H), 1.85 (septet, J = 6.8
Hz, 1H), 1.07 (d, J = 6.4 Hz, 6H); 13C{1H} NMR (C6D5Cl, 100.6 MHz,
23 °C) δ 68.41, 45.68, 26.46, 20.73.
Data for hemiaminal ether (7%) (entry 16): 1H NMR (C6D5Cl, 400
MHz, 23 °C, selected data) δ 5.72 (s, 1H), 4.79 (m, 1H), 3.96ꢀ3.74 (m,
4H); 13C{1H} NMR (C6D5Cl, 100.6 MHz, 23 °C, selected data) δ
86.08, 52.21.
Data for N,N,2-trimethylprop-1-en-1-amine as a side product in entry
1 (Table 2): 1H NMR (C6D6, 400 MHz, 23 °C): δ 5.38 (s, 1H), 2.39 (s,
6H), 1.79 (s, 3H), 1.66 (s, 3H); 13C{1H} NMR (C6D6, 100.6 MHz,
23 °C) δ 137.3, 121.0, 45.0, 21.9, 16.9.
Data for N,N-dibenzyl-1-(naphthalene-1-yl)methanamine (entry
1
17): H NMR (C6D5Cl, 400 MHz, 23 °C) δ 8.19ꢀ7.24 (m, 17H,
overlap with solvent peaks), 3.97 (s, 2H), 3.58 (s, 4H); 13C{1H} NMR
(C6D5Cl, 100.6 MHz, 23 °C, selected data) δ 58.67, 56.95.
Data for N,N-dibenzyl-1-cyclopropylmethanamine (entry 18):
1H NMR (C6D5Cl, 400 MHz, 23 °C) δ 7.48ꢀ7.24 (m, 10H, overlap
with solvent peaks), 3.82 (s, 4H), 2.51 (d, J = 6.4 Hz, 2H), 1.08 (br s,
1H), 0.61 (d, J = 7.2 Hz, 2H), 0.19 (br s, 2H); 13C{1H} NMR (C6D5Cl,
100.6 MHz, 23 °C) δ 140.43, 128.95, 128.01, 126.86, 58.50, 58.46,
8.72, 4.15.
1
Data for N,N-dimethylbenzylamine (entry 4): H NMR (C6D5Cl,
400 MHz, 23 °C) δ 7.49ꢀ7.35 (m, 5H, overlap with solvent peaks), 3.53
(s, 2H), 2.35 (s, 6H); 13C{1H} NMR (C6D5Cl, 100.6 MHz, 23 °C) δ
139.70, 128.82, 128.12, 126.85, 64.43, 45.22.
Data for 1-((dimethylsilyl)oxy)-N,N-dimethyl-1-phenylmethan-
amine as a product of first hydrosilylation: 1H NMR (C6D6, 400 MHz,
23 °C) δ 7.57ꢀ7.28 (m, 5H, overlap with solvent peaks), 5.51 (s, 1H),
652
dx.doi.org/10.1021/ja209567m |J. Am. Chem. Soc. 2012, 134, 640–653

Journal of the American Chemical Society
ARTICLE
1
Data for N,N-dibenzyl-1-(furan-2-yl)methanamine (entry 19): H
NMR (C6D5Cl, 400 MHz, 23 °C) δ 7.64ꢀ7.39 (m, 11H, overlap with
solvent peaks), 6.45 (s, 1H), 6.32 (s, 1H), 3.77 (s, 6H); 13C{1H} NMR
(C6D5Cl, 100.6 MHz, 23 °C) δ 152.94, 141.77, 139.70, 128.35, 128.25,
127.04, 110.17, 108.63, 57.79, 49.22.
Beller, M. Angew. Chem., Int. Ed. 2011, 50, 2–10. (q) Bower, S.; Kreutzer,
K. A.; Buchwald, S. L. Angew. Chem., Int. Ed. Engl. 1996, 35, 1515–1516.
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6064. (b) Yang, J.; White, P. S.; Brookhart, M. J. Am. Chem. Soc. 2008,
130, 17509–17518. (c) Park, S.; Brookhart, M. Chem. Commun. 2011,
47, 3643–3645. (d) Yang, J.; Brookhart, M. J. Am. Chem. Soc. 2007,
129, 12656–12657. (e) Yang, J.; White, P. S.; Schauer, C.; Brookhart, M.
Angew. Chem., Int. Ed. 2007, 119, 6253–6255. (f) Yang, J.; Brookhart, M.
Adv. Synth. Catal. 2009, 351, 175–187.
Data for (E)-1-(4-(phenyldiazenyl)benzyl)piperidine (entry 20): 1H
NMR (C6D6, 400 MHz, 23 °C) δ 8.10ꢀ8.07 (m, 4H), 7.48 (d, J = 8.0
Hz, 2H), 7.33ꢀ7.22 (m, 3H, overlap with a solvent peak), 3.39 (s, 2H),
2.35 (br s, 4H), 1.57 (q, J = 5.5 Hz, 4H), 1.42 (br s, 2H); 13C{1H} NMR
(C6D6, 100.6 MHz, 23 °C) δ 153.0, 152.0, 143.0, 130.6, 129.3, 128.9,
123.0, 122.9, 63.4, 54.6, 26.2, 24.5.
(6) The cationic amine complex is quantitatively formed in situ
within 5 min at 23 °C by reaction of 1 with Et3SiH, followed by adding
NEt3. The 31P shift (δ 175.2) for this complex is very close to that of the
cationic iridium complex coordinated with the amide (δ 176.5) and with
C6D5Cl (δ 177.0).5d
’ ASSOCIATED CONTENT
(7) HEt2SiOtBu as a result of the reduction of HOtBu with Et2SiH2
1
has been observed in the reaction mixture by H and 13C{1H} NMR
S
Supporting Information. Figures giving variable-temperature
b
spectroscopy.
1H NMR (hydride region) spectra of a mixture of 3and 4and product
1H NMR and 13C NMR spectra. This material is available free of
charge via the Internet at http://pubs.acs.org.
(8) (a) G€ottker-Schnetmann, I.; White, P. S.; Brookhart, M. Organo-
metallics 2004, 23, 1766–1776. (b) Hebden, T. J.; Goldberg, K. I.;
Heinekey, D. M.; Zhang, X.; Emge, T. J.; Goldman, A. S.; Krogh-
Jespersen, K. Inorg. Chem. 2010, 49, 1733–1742.
’ AUTHOR INFORMATION
(9) (a) Bart, S. C.; Lobkovsky, E.; Chirik, P. J. J. Am. Chem. Soc. 2004,
126, 13794–13807. (b) Delpech, F.; Sabo-Etienne, S.; Chaudret, B.;
Daran, J. C. J. Am. Chem. Soc. 1997, 119, 3167–3168. (c) Lin, Z. Chem.
Soc. Rev. 2002, 31, 239–245. (d) Schneider, J. J. Angew. Chem., Int. Ed.
1996, 35, 1068–1075. (e) Taw, F. L.; Bergman, R. G.; Brookhart, M.
Organometallics 2004, 23, 886–890. (f) Liang, X.; Crabtree, R. H. J. Am.
Chem. Soc. 1989, 111, 2527–2535. (g) Schubert, U. Adv. Organomet.
Chem. 1990, 30, 151–187. (h) Corey, J. Y.; Braddock-Wilking, J. Chem.
Rev. 1999, 99, 175–292. (i) Duckett, S. B.; Perutz, R. N. J. Chem. Soc.,
Chem. Commun. 1991, 28–31. (j) Tanke, R. S.; Crabtree, R. H.
Organometallics 1991, 10, 415–418.
Corresponding Author
mbrookhart@unc.edu.
’ ACKNOWLEDGMENT
We thank the National Science Foundation (No. CHE
1010170) for support of this work.
(10) Another possible structure for 4 is an Ir(III) species containing
an η2-H2 ligand. This seems less likely in that the η2-silane would be a
better σ donor than H2. Nevertheless, we have prepared a partially
deuterated isotopomer of 4 (4-d2) and find no measurable HꢀD
coupling in the 1H NMR spectrum, ruling out η2-H2 bonding.
(11) This salt can be synthesized by mixing (Et2O)HB(C6F5)4 and
Et3N (20 equiv) in toluene at 22 °C, followed by removing volatiles in
vacuo to give a white powder.
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