Formation of Enamines via Catalytic Dehydrogenation by Pincer-Iridium Complexes

Article abstract of DOI:10.1021/acs.joc.9b02846

Di-isopropylphosphino-substituted pincer-ligated iridium catalysts are found to be significantly more effective for the dehydrogenation of simple tertiary amines to give enamines than the previously reported di-t-butylphosphino-substituted species. It is

Full text of DOI:10.1021/acs.joc.9b02846

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Formation of Enamines via Catalytic Dehydrogenation by Pincer-
Iridium Complexes
Yansong J. Lu, Xiawei Zhang, Santanu Malakar, Karsten Krogh-Jespersen, Faraj Hasanayn,
and Alan S. Goldman*
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ABSTRACT: Di-isopropylphosphino-substituted pincer-ligated iridium catalysts
are found to be significantly more effective for the dehydrogenation of simple
tertiary amines to give enamines than the previously reported di-t-butylphosphino-
substituted species. It is also found that the di-isopropylphosphino-substituted
complexes catalyze dehydrogenation of several β-functionalized tertiary amines to
give the corresponding 1,2-difunctionalized olefins. The di-t-butylphosphino-
substituted species are ineffective for such substrates; presumably, the marked
difference is attributable to the lesser crowding of the di-isopropylphosphino-
substituted catalysts. Experimentally determined kinetic isotope effects in
conjunction with DFT-based analysis support a dehydrogenation mechanism
involving initial pre-equilibrium oxidative addition of the amine α-C−H bond followed by rate-determining elimination of the β-C−
H bond.
of (iPr4PCP)Ir (2) and derivatives are often catalytically more
1. INTRODUCTION
active.7,8 In this article, we report that (iPr4PCP)IrHn (n = 2,
The ability to effect selective catalytic conversions of typically
4)7a,8 and the corresponding p-methoxy-substituted derivative
unreactive C−H bonds has emerged as one of the major
(MeO-iPr4PCP)IrHn (3)9 are significantly more effective than
frontiers in organic chemistry in recent years, offering the
tBu4PCP)IrH2 as catalysts for dehydrogenation of tertiary
promise of simple atom-economical methods for the synthesis
(
of valuable functionalized organic compounds.1 Pincer-ligated
iridium complexes have been studied intensively in this
context,2 mostly as highly active and robust catalysts for the
dehydrogenation of alkanes, but also for the dehydrogenation
of aliphatic C−C linkages in molecules other than alkanes. We
have previously reported3 the synthesis of enamines via
dehydrogenation of the corresponding tertiary amines
catalyzed by (tBu4PCP)Ir (1, R4PCP = κ3-C6H3-2,6-
(CH2PR2)2),4 using a sacrificial hydrogen acceptor (Scheme
1). Enamines are highly valuable synthons, used extensively as
nucleophiles for the selective formation of C−C bonds by
Michael reactions, as Diels−Alder dienophiles, and in a wide
range of other reactions.5
amines to enamines. We also report that with these sterically
much less demanding catalysts, we are able to dehydrogenate
crowded 1,2-difunctionalized saturated C−C linkages. This
represents a novel approach to the corresponding 1,2-
difunctionalized olefins, which are attractive precursors for
further functionalization reactions such as cycloadditions,
leading to building blocks that cannot be efficiently synthesized
via known methods.
We also report herein the results of combined mechanistic
experimental and computational (DFT) studies. In con-
junction, these results support a mechanism for amine
dehydrogenation, which proceeds analogously to that for
alkane dehydrogenation but with a lower activation barrier.
Specifically, the results are strongly indicative of a pathway
operating via addition of an amine α-C−H bond, followed by
rate-determining elimination of a hydrogen atom at the amine
β-position.
Subsequent to the early pincer-Ir dehydrogenation work
with precursors of (tBu4PCP)Ir,4,6 it was found that precursors
Scheme 1. Reported Synthesis of Enamines via Catalytic
Dehydrogenation
Received: October 19, 2019
Published: January 28, 2020
https://dx.doi.org/10.1021/acs.joc.9b02846
© 2020 American Chemical Society
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Table 1. Dehydrogenation of Tertiary Amines Catalyzed by (MeO-iPr4PCP)IrHn (with Previously Reported3 Results Obtained
a
with (tBu4PCP)IrH2 Shown for Comparison)
a
All reactions were conducted with 0.1 M amine substrate in p-xylene-d10 solvent and were monitored by 31P NMR and 1H NMR spectroscopies
1
over the course of the reaction. Yields were determined by H NMR spectroscopy.
°C) are significantly higher than those found for (tBu4PCP)-
2. RESULTS AND DISCUSSION
IrHn.7c
2.1. Dehydrogenation of Tertiary Amines. In our
In general, the same reactivity patterns were observed with
previous report of the transfer dehydrogenation of tertiary
(MeO-iPr4PCP)Ir as with (tBu4PCP)Ir. This includes complete
amines catalyzed by (tBu4PCP)IrHn,3 we found that a relatively
selectivity for dehydrogenation of an N-ethyl group versus an
high catalyst loading was generally required to obtain good
N-i-propyl group (entry 1) and the failure to dehydrogenate
yields. With (iPr4PCP)IrHn and the same substrates inves-
tigated previously, using NBE as a hydrogen acceptor,
the piperidine ring in either N-methylpiperidine or N-
ethylpiperidine. The greater effectiveness of (MeO-iPr4PCP)Ir
satisfactory yields were generally achieved with a catalyst
as compared with (tBu4PCP)Ir, however, was much more
loading of only 2%, although higher temperatures and
somewhat longer reaction times were generally required
marked for the dehydrogenation of n-propyl groups (entry 4)
and the i-propyl group (entry 5). This is likely attributable to
lesser crowding at the metal center of (MeO-iPr4PCP)Ir,
(Table 1). Note that with these same higher reaction
temperatures and longer times, with (tBu4PCP)IrHn (as
opposed to (iPr4PCP)IrHn), the yields of the reactions were
actually lowered, not increased. The need for higher temper-
ature with (iPr4PCP)IrHn is likely a consequence of stronger
binding of olefin (either H-acceptor or enamine) to the
sterically less demanding catalyst. Very high yields obtained
with (iPr4PCP)IrHn, much higher than with (tBu4PCP)IrHn,
have also been reported for alkane transfer dehydrogenation
using the strongly binding hydrogen acceptors ethylene and
propylene; in this case too, the optimal temperatures (>200
relative to (tBu4PCP)Ir, being particularly favorable for
dehydrogenation of C−C linkages more crowded than the
ethyl group.
As observed with (tBu4PCP)Ir-catalyzed reactions, all of the
enamine products degraded, usually within several hours, after
being isolated from the catalyst (via vacuum transfer of
enamine and solvent); this behavior is consistent with the
known instability of simple enamines.5a,10 Thus, it is
remarkable that the enamines are stable at the high
temperature (120 °C) at which they are formed. In view of
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that stability at elevated temperatures, however, it is not
surprising that the enamines are indefinitely stable, while still
in the presence of the Ir complex, at room temperature. As
previously3 proposed, it seems probable that the Ir complex
inhibits a chain reaction leading to loss of the enamine,
perhaps by scavenging chain initiators.
2.2. Dehydrogenation To Afford 1,2-Difunctional
Olefins. 1,2-Difunctional olefins are of great interest as
versatile intermediates in organic synthesis for various
cycloadditions.11 Electron-rich 1,2-difunctional olefins in
particular can undergo useful [2 + 1] cycloadditions (cyclo-
propanation, Simmons−Smith type reaction)12 and [2 + 2],13
[3 + 2],14 and [4 + 2]15 cycloadditions, to afford various
compounds that serve as novel building blocks for organic
synthesis.
In this context and that of tertiary amine dehydrogenation,
we considered the dehydrogenation of β-functionalized tertiary
amines. We first attempted the catalytic dehydrogenation of
the relatively sterically hindered diamine substrate, N,N,N′,N′-
tetramethyl-ethane-1,2-diamine (tetramethylethylenediamine;
TMEDA) (eq 1). Various conditions were screened, including
the use of NBE, TBE, and camphene as hydrogen acceptors;
significant yields of the desired product were achieved only
with NBE.16
success noted above with 1,2-difunctionalized substrates such
as TMEDA, we attempted dehydrogenation of a bulky
bis(trimethylsilyl)diether substrate (entry 6) and were pleased
to obtain excellent yields.
Entries 1, 4, 5, and 6 in Table 2 represent new chemical
transformations. Only a single isomer (E) was obtained from
each of the four reactions, as indicated in Table 2.
N,N′-Dimethyl-N,N′-dibenzyl-ethylene-1,2-diamine did not
undergo any reaction (entry 2), which is likely attributable to
steric hindrance by the benzyl substituents as compared with
the methyl groups. 1,4-Dimethylpiperazine did not undergo
dehydrogenation (entry 3) in accordance with the failure,
reported above, to dehydrogenate N-methylpiperidine and N-
ethylpiperidine at the ring position.
2.3. Mechanistic Studies. The apparently high reactivity
of the acyclic amine substrates, indicated by the good product
yields, was confirmed in a competition experiment between
N,N-di(isopropyl)ethylamine (60 mM) and cyclooctane
(COA; 600 mM) (Scheme 3).3,22 The latter substrate is
frequently used in alkane dehydrogenation studies because of
its anomalously low enthalpy of dehydrogenation.2,4,6
The reaction was conducted as a stoichiometric competition
reaction of (tBu4PCP)Ir(H)(Ph) (which is known to act as an
effective precursor of the fragment (tBu4PCP)Ir even at or
below room temperature23), in the absence of the hydrogen
1
acceptor, allowing characterization by H NMR spectroscopy
at very low conversions of COA and di(isopropyl)ethylamine.
This procedure favored the observation of cyclooctene and
N,N-di(isopropyl)vinylamine in a kinetically determined ratio
rather than a thermodynamic distribution. Indeed, the ratio of
cyclooctene to N,N-di(isopropyl)vinylamine remained roughly
constant at 1:2.0, even from the earliest reaction times.
Catalysts 1−5 (Scheme 2) were screened for the reaction
outlined in eq 1; among these catalysts, 2 and 3 proved to be
similarly effective. Catalyst 1 gave no observable product,
presumably highlighting the importance of steric factors for
dehydrogenation of this sterically hindered substrate
(TMEDA). Catalyst 4 gave some product but less than 2 or
3. Catalyst 5 apparently polymerized the hydrogen acceptor
(NBE),17 and the desired dehydrogenation products were not
detected.
Other 1,2-difunctionalized ethane derivatives were inves-
tigated. Vinyl acrylates have been found to form stable,
catalytically inactive, adducts with (tBu4PCP)Ir.18 We were
therefore pleasantly surprised that some, albeit limited,
catalytic dehydrogenation of methyl 3-(dimethylamino)-
propanoate (entry 4) was achieved, likely due to steric
hindrance preventing the formation of such inactive adducts.
Relatedly, nitriles appear to coordinate fairly strongly to
(RPCP)Ir fragments, yet a very good yield (84%) was obtained
with the substrate 3-(dimethylamino)propanenitrile (entry 5).
Our previous attempts to dehydrogenate ethers have for the
most part been unsuccessful apparently due to the formation of
vinyl ether adducts. Some success has been achieved with ether
dehydrogenation.19 Most notably in the context of this work,
Brookhart and co-workers found that (iPr4PCP)Ir could effect
dehydrogenation of acyclic ethers,20 and Huang and co-
workers reported21 dehydrogenation of cyclic amines and
ethers with the related (iPr4PSCOP)Ir species. Inspired by the
i
Dehydrogenation of the Pr2NEt ethyl group is thus found
(after accounting for the 10:1 excess of COA) to be 20 times
more rapid than dehydrogenation of COA on a per mole basis;
on a per C−C bond basis, the ratio is therefore 160.3
Competition experiments between N,N-di(alkyl)ethylamines
reveal that the rate of dehydrogenation of the N-ethyl group is
dependent upon the ancillary N-alkyl group as follows: i-propyl
> ethyl > methyl in the ratio of approximately 140:7:1.3 The
trend is opposite to what would be expected based on
consideration of steric factors. It is not obvious how this trend
would be reconciled with the generally accepted reaction
pathway for alkanes, which proceeds via oxidative addition
followed by β-hydrogen elimination.2 More generally, the
origin of the much greater reactivity of amines compared with
alkanes is not obvious in the context of such a mechanism. We
therefore considered that alternative pathways might be
operative, proceeding, for example, via radicals or via electron
transfer.
To address this fundamental mechanistic question, we first
conducted a series of kinetic isotope effect (KIE) experiments.
i
N,N-di(isopropyl)ethylamine isotopologues Pr2N(CD2CD3),
i
iPr2N(CD2CH3), and Pr2N(CH2CD3) were synthesized. In a
competitive catalytic reaction (90 °C), (tBu4PCP)IrHn (10.2
Scheme 2. Pincer-Iridium Catalysts Screened
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a
Table 2. Dehydrogenation Reactions Catalyzed by (iPr4PCP)Ir (2) with NBE as Hydrogen Acceptor
a
All reactions were run in p-xylene-d10, and NBE was used as a hydrogen acceptor. All yields were determined by 1H NMR spectroscopy. A: 0.05
mmol substrate (0.1 M), 2.3 equiv (0.115 mmol) NBE, 15 mol % (4.0 mg) 2, 143 °C, 45 h, unless noted otherwise. B: 0.05 mmol substrate (0.1
M), 2.0 equiv (0.10 mmol) NBE, 25 mol % (6.6 mg) 2, 143 °C, 24 h.
i
Scheme 3. Competition Experiment To Determine Relative Reactivity of COA versus Pr2NEt
Scheme 4. Pathway for Amine Dehydrogenation by 1 Consistent with Observed Isotope Effects
i
i
mM), TBE (250 mM), Pr2N(C2H5) (30.7 mM), and Pr2N-
(C2D5) (61.4 mM) were allowed to react; kC2H5/kC2D5 was
found to be 7.0.3 A stoichiometric competition reaction with
this context, we conducted a computational study to elucidate
the detailed energetics of this putative reaction mechanism.
2.4. Computational Studies. A series of electronic
structure calculations based on density functional theory
(DFT; M06 level, see Computational Methods) were
conducted for dehydrogenation pathways proceeding through
(
tBu4PCP)Ir(H)(Ph), conducted in analogy with the above
described experiment with COA (Scheme 3), was conducted
with iPr2N(C2H5) (146 mM) and iPr2N(CH2CD3) (291 mM)
and was found to give a KIE of kC2H5/kCH2CD3 = 3.7. In another
such stoichiometric competition reaction, the reaction of
i
oxidative addition of an aminoethyl C−H bond of Pr2NEt or
Me2NEt to (tBu4PCP)Ir, followed by β-H elimination to give
the corresponding vinyl amines. We also calculated, for
comparison, the energy profiles of pathways for dehydrogen-
ation of COA and n-butane and for the alkanes that are
i
i
(
tBu4PCP)Ir(H)(Ph) with Pr2N(C2H5) (146 mM) and Pr2N-
(CD2CH3) (291 mM), the value of kC2H5/kCD2CH3 was found
to be 2.0. Thus, kC2H5/kC2D5 (7.0) is approximately equal to the
product of the KIE values kC2H5/kCH2CD3 (3.7) and kC2H5
kCD2CH3 (2.0).
The results of these isotope effect experiments clearly imply
that cleavage of both α- and β-C−H bonds occurs during or
preceding the rate-determining step. Thus, they argue against a
mechanism proceeding via rate-determining electron transfer
or abstraction of an H atom from the amine.
i
/
isostructural with Pr2NEt and Me2NEt, namely, 3-ethyl-2,4-
dimethylpentane and isopentane, respectively (corresponding
products shown in Scheme 5). For all of these substrates
except COA, two distinct dehydrogenation pathways of this
type are possible, and both were investigated computationally
(Scheme 6): pathway a, oxidative addition of a primary C−H
bond followed by β-H-elimination of the adjacent secondary
The value of 2.0 for kC2H5/kCD2CH3 is consistent with an
equilibrium isotope effect (preceding a rate-determining step)
for a reaction in which H is transferred from carbon to a metal
atom, while the value of 3.7 for kC2H5/kCH2CD3 indicates a rate-
limiting kinetic isotope effect.24 These isotope effects are thus
consistent with a pathway featuring reversible oxidative
addition of the α-C−H bond followed by rate-determining
β-H-elimination (Scheme 4). It is still not obvious, however,
why such a mechanism would favor amines over alkanes. In
Scheme 5. Products of Dehydrogenation of Various
Substrates for Which Dehydrogenation Pathways Were
Calculated
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Scheme 6. Putative Pathways for Dehydrogenation of Amines and Alkanes Examined by DFT Calculations
C−H bond, and pathway b, oxidative addition of the
secondary C−H bond followed by β-H-elimination of the
adjacent primary C−H bond.
for pathways a and b, respectively, are both in good agreement
with this value.
KIEs were calculated for dehydrogenation of the Pr2NEt
i
isotopologues that were experimentally investigated. For
For all substrates and for either pathway, the energy of the
TS for the second step, β-H elimination, is higher than that for
the first C−H activation step. Thus β-H-elimination is
calculated to be the rate-determining step for the formation
of trans-(tBu4PCP)IrH2(olefin) ([Ir]H2(ene)). The Gibbs free
energies (relative to (tBu4PCP)Ir plus free substrate) of the TS
for the C−H addition, the C−H addition intermediate, the TS
for β-H-elimination, the intermediate trans-(tBu4PCP)-
IrH2(olefin), and the free olefin product plus (tBu4PCP)IrH2
are given in Table 3.
pathway a, at 50 °C, the KIE was calculated to be 2.5 for
i
the terminal position of the aminoethyl group of Pr2NEt
(kC2H5/CH2CD3) and 5.2 for the methylene group
(kC2H5/CD2CH3); for full isotopic substitution of the ethyl
group, kC2H5/C2D5 = 13.1 at 50 °C and 9.9 at 90 °C. For
pathway b, the calculated values are kC2H5/CH2CD3 = 3.5,
k
C2H5/CD2CH3 = 2.9, and kC2H5/C2D5 = 10.1 (50 °C) and 7.8 (90
°C). The experimental KIEs, discussed above, are kC2H5/CH2CD3
= 3.7, kC2H5/CD2CH3 = 2.0 (50 °C), and kC2H5/C2D5 = 7.0 (90
°C). The experimental values are clearly inconsistent with the
values calculated for pathway a. Conversely, they are in good
agreement with the calculations for pathway b; we believe that
this agreement offers very strong support for this pathway.
The difference in barrier heights computed for pathways a
and b is, however, small in all cases (1−3 kcal/mol; Table 3),
testing the reliability of the computational methods. Indeed,
for iPr2NEt, pathway a is calculated to have a Gibbs free-energy
barrier that is 1.3 kcal/mol lower than pathway b (Table 3).
We consider the magnitude of this discrepancy to be well
within the overall limits of uncertainty for the applied
computational methodology.25,26 The rate-determining TS
(β-H elimination) obtained for iPr2NEt dehydrogenation along
pathway b is more sterically crowded than the corresponding
TS along pathway a, and it seems plausible that the incomplete
treatment of dispersive interactions offered by the M06
functional contributes to the discrepancy. Similarly, the slightly
Table 3. Calculated Gibbs Free Energies (kcal/mol; 50 °C;
1.0 M Substrate) of Key Intermediates and TSs for
Dehydrogenation of Various Substrates via Pathways a and
b Outlined in Scheme 6
TS CH-
addtn
C−H
TS β-
[Ir]
[Ir]H2
substrate
pathway
adduct H-elim H2(ene) + ene
iPr2NEt
iPr2NEt
Me2NEt
Me2NEt
a
b
a
b
a
20.1
29.9
19.5
25.0
23.8
14.2
29.1
13.2
23.9
18.3
31.4
32.6
30.8
32.0
36.7
20.0
20.0
20.9
20.9
23.7
7.1
7.1
6.0
6.0
5.6
N-Me-
piperidine
N-Me-
piperidine
b
28.8
22.7
41.5
23.7
5.6
n-butane
n-butane
iPr2CHEt
iPr2CHEt
Me2CHEt
Me2CHEt
COA
a
b
a
b
a
b
22.0
29.3
20.7
30.3
22.8
27.5
27.2
16.1
20.9
17.2
30.0
14.6
27.8
23.4
35.2
36.8
36.3
32.9
34.5
36.7
34.9
22.9
22.9
22.5
22.5
22.3
22.3
28.0
12.3
12.3
11.6
11.6
12.4
12.4
3.7
i
higher calculated barriers for dehydrogenation of Pr2NEt
versus Me2NEt (ΔΔG‡
= approximately 0.6 kcal/mol for
either pathway a or b) may be at least in part due to a very
approximate treatment of dispersive interactions.
50 °C
The calculations offer a straightforward explanation for the
selectivity for dehydrogenation of amines compared with
alkanes. The energies of the C−H addition products and their
barriers to β-H-elimination vary greatly between substrates and
pathways. In contrast, the energies of the transition states TS
β-H-elim (particularly for pathway b) correlate fairly well with
the energies of the intermediates to which they connect, the β-
H-elimination products, [Ir]H2(ene). In particular, the
intermediates resulting from acyclic amine dehydrogenation
are the lowest in free energy of those in Table 3, as are the
corresponding transition states TS β-H-elim. Consistent with
this correlation of free energies, the geometries of the
transition states TS β-H-elim are notably similar to those of
the intermediates [Ir]H2(ene) as shown in Figure 1 for
The calculated free energies shown in Table 3 can be
considered in the context of the experimental observations
described above. Relative rates for all substrates are determined
by the free energy of the TS for β-H-elimination (TS β-H-
elim); these TS energies are the lowest for the acyclic amines,
consistent with the qualitative observation that these amines
are more reactive than alkanes. For N-Me-piperidine, TS β-H-
elim is calculated to be equal or higher in free energy than for
the alkanes studied, consistent with its failure to undergo
dehydrogenation. More quantitatively, as described above, in
i
the competition experiment between Pr2NEt and COA, a
i
relative rate factor of 160 per C−C bond favoring the amine
dehydrogenation of Pr2NEt. The product-like nature of TS β-
was determined, which corresponds to ΔΔG‡
= 3.3 kcal/
H-elim also helps to rationalize why the free energy of this TS
is very similar for pathways a and b despite the fact that the
50 °C
mol. The calculated values of ΔΔG‡50°C, 3.5 and 2.2 kcal/mol
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Figure 1. Selected bond distances (in Å) and angles for the products of C−H bond addition (C−H adduct), the TSs for β-H elimination (TS β-H-
i
elim), and the resulting intermediate ([Ir]H2(ene)) for the reaction of (tBu4PCP)Ir with Pr2NEt via pathway a and pathway b.
different TSs are derived from C−H addition products, which
have very different free energies in the two pathways.
4. EXPERIMENTAL SECTION
4.1. General Information. All reactions, recrystallizations, and
routine manipulations were conducted under an inert atmosphere
using an argon-filled glove box or by using standard Schlenk
techniques under an argon atmosphere. J. Young NMR tubes were
used for catalytic dehydrogenation reactions. Reagent grade solvents
were used and dried according to established methods and then
degassed with argon. All NMR solvents were dried, vacuum-
transferred, and stored in an argon-filled glove box.
If the variations in the energies of TS β-H-elim can be
rationalized in terms of the energies of the intermediates,
[Ir]H2(ene), then the question arises as to what may explain
the variations in energies of these intermediates. A comparison
between the amines and the isostructural alkanes is probably
most informative in this context. We note that the difference
between the relative energies of the amine dehydrogenation
intermediates and the isostructural alkane dehydrogenation
intermediates, [Ir]H2(ene), is approximately 2 kcal/mol
(Table 3). This compares with a difference of approximately
5 kcal/mol for the relative energies of the free enamine and
alkene products, attributable to conjugation between the
amino group and the C−C π-system. We presume that the
lower energy of the [Ir]H2(ene) amine dehydrogenation
products simply reflects the lower energy of the free
dehydrogenated species (with the difference mitigated by
stronger binding of the enamine); this same effect is therefore
ultimately responsible for the faster kinetics of dehydrogen-
ation of amines compared with alkane. For the cyclic species
studied, COA and N-methylpiperidine, in contrast, the
corresponding free olefins are low in energy. However,
consistent with the relatively low reactivity of these substrates,
their corresponding Ir-olefin adducts are higher in free energy
than the adducts of the linear olefins, presumably for steric
reasons.
1H, 31P{1H}, and 13C{1H} NMR spectra were obtained on Varian
300-, 400-, or 500-MHz spectrometers. H and 13C NMR chemical
1
shifts are reported in ppm downfield from tetramethylsilane and were
referenced to residual protiated (1H) or deuterated solvent (13C).
Catalysts 1-Hn,4 2-Hn,7a 3-Hn,9 4-Hn,7b and 5-Hn,7b and (tBu4PCP)-
Ir(H)Ph23 were prepared as described in the literature. Simple amines
were purchased from Sigma-Aldrich. N,N-diisopropylpropylamine and
isotopically labeled N,N-diisopropylethylamines i-Pr2N(C2D5), i-
Pr2N(CD2CH3), and i-Pr2N(CH2CD3) were synthesized according
to a literature procedure.27 All amines were purified by treating with
Na/K alloy, followed by vacuum distillation. All substrates were
stored over molecular sieves before use.
4.2. General Procedure for Catalytic Dehydrogenation. All
substrates, hydrogen acceptors, catalysts, and solvents were loaded
into a J. Young NMR tube in a glovebox under an argon atmosphere.
1
A H NMR spectrum was acquired at time zero (t0), and the NMR
tube was heated in an oil bath. The reaction progress was monitored
1
by H NMR spectroscopy. Yields were calculated based on relevant
1
peak areas in the H NMR spectrum.
For the dehydrogenation of simple tertiary amines, the solvent was
removed followed by bulb-to-bulb distillation of the higher-MW
products to give a colorless oil that included any unreacted amine and
multiply dehydrogenated product as well as monoene. The mixture
was subjected to mass spectroscopic as well as NMR analysis, but no
attempts were made to isolate the monoene product.3
3. CONCLUSIONS
Precursors of (iPr4PCP)Ir and (MeO-iPr4PCP)Ir are efficient
catalysts for dehydrogenation of simple tertiary amines to give
enamines, significantly more effective than precursors of the
previously reported, more sterically hindered, (tBu4PCP)Ir
fragment. They are also found to catalyze (unlike (tBu4PCP)Ir)
the dehydrogenation of β-functionalized tertiary amines to give
the corresponding 1,2-difunctionalized olefins, which are of
interest for further chemical manipulations such as cyclo-
addition reactions.11−15 Combined mechanistic and computa-
tional studies indicate that the amine dehydrogenations
proceed via C−H oxidative addition at the N-bound carbon,
followed by rate-limiting β-H elimination.
1
N,N-Di(isopropyl)vinylamine: H NMR (300 MHz, p-xylene-d10,
δ): 6.10 (dd, 15.6 Hz, 9.2 Hz, 1H), 3.83 (d, 9.2 Hz, 1H), 3.82 (d, 15.6
Hz, 1 H), 3.41 (m, 6.5 Hz, 2H), 1.03 (d, 6.5 Hz, 12H). MS (EI) m/z:
127(parent), 112, 99, 70, 56.3
1
N,N-Dimethylvinylamine: H NMR (300 MHz, p-xylene-d10, δ):
6.01 (dd, JHH = 15.2 Hz, 8.4 Hz, 1 H), 3.84 (d, JHH = 8.4 Hz, 1H),
3.74 (d, JHH = 15.2 Hz, 1H), 2.39 (s, 6H). MS (EI) m/z: 71(parent),
58, 56, 44.3
N,N-Diethylvinylamine: 1H NMR (300 MHz, p-xylene-d10, δ): 6.03
(dd, JHH = 15.2 Hz, 9.2 Hz, 1H), 3.78(d, JHH = 9.2 Hz, 1H), 3.75(d,
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J
HH = 15.2 Hz, 1H), 2.81(q, JHH = 7.0 Hz, 4H), 1.05(t, JHH = 7.0 Hz,
Authors
6H). MS (EI) m/z: 99(parent), 84, 73, 71, 56.3
Yansong J. Lu − Department of Chemistry and Chemical
Biology, Rutgers The State University of New Jersey, New
Brunswick, New Jersey 08903, United States
Xiawei Zhang − Department of Chemistry and Chemical
Biology, Rutgers The State University of New Jersey, New
Brunswick, New Jersey 08903, United States
N,N-Divinylethylamine: 1H NMR (300 MHz, p-xylene-d10, δ): 6.00
(dd, JHH = 15.6 Hz, 9.0 Hz, 2 H), 3.93 (d, JHH = 15.6 Hz, 2 H), 3.86
(d, JHH = 9.0 Hz, 2H), 3.14 (q, JHH = 7.0 Hz, 2H), 1.02 (t, JHH = 7.0
Hz, 3 H). MS (EI) m/z: 97(parent), 83, 70, 56.3
N,N-Dipropyl-(E)-1-propenylamine: 1H NMR (300 MHz, p-
xylene-d10, δ): 5.89 (dd, JHH = 13.5 Hz, 1.5 Hz, 1H), 4.18 (qd, JHH
Santanu Malakar − Department of Chemistry and Chemical
Biology, Rutgers The State University of New Jersey, New
Brunswick, New Jersey 08903, United States
Karsten Krogh-Jespersen − Department of Chemistry and
Chemical Biology, Rutgers The State University of New Jersey,
New Brunswick, New Jersey 08903, United States
Faraj Hasanayn − Department of Chemistry, American
University of Beirut, Beirut 1107 2020, Lebanon; orcid.org/
0000-0003-3308-7854
= 6.3 Hz, 13.5 Hz, 1 H), 2.75 (t, JHH = 7.2 Hz, 4H), 1.85 (dd, JHH
=
6.3 Hz, 1.5 Hz, 3H), 1.48 (tq, JHH = 7.2 Hz, 7.2 Hz, 4H), 0.98 (t, JHH
= 7.2 Hz, 6H).3
N,N-Di-(E)-1-propenylpropylamine: 1H NMR (300 MHz, p-
xylene-d10, δ): 5.91 (d, JHH = 13.6 Hz, 2 H), 5.38 (m, JHH = 13.6
Hz, 6.4 Hz, 2 H), 3.04 (t, JHH = 7.6 Hz, 2 H), 1.75 (d, JHH = 6.4 Hz, 6
H), 1.31 (m, 2H), 1.01 (t, JHH = 6.8 Hz, 3 H). MS(EI) m/z:
139(parent), 124, 110, 98, 70.3
N-Vinylpiperidine: 1H NMR (300 MHz, p-xylene-d10, δ): 5.99 (dd,
J
HH = 15.3 Hz, 8.7 Hz, 2H), 3.90 (d, JHH = 15.3 Hz, 1H), 2.88(d, JHH
= 8.7 Hz, 1H), 2.68 (t, JHH = 5.3 Hz, 4H), 1.60 (m, 6H).3
(E)-N,N,N′,N′-Tetramethylethene-1,2-diamine: 1H NMR (400
MHz, p-xylene-d10, δ): 5.44 (s, 2H), 2.5 (s, 12H).
(E)-3-(Dimethylamino)acrylonitrile: 1H NMR (400 MHz, p-
xylene-d10, δ): 3.49 (d, J = 13.6 Hz, 1H), 6.34 (d, J = 13.6 Hz,
1H), 2.60 (s, 6H).
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.9b02846
Notes
The authors declare no competing financial interest.
A version of this manuscript was filed on the preprint server
ChemRxiv.35
1
Methyl (E)-3-(Dimethylamino)acrylate: H NMR (500 MHz, p-
xylene-d10, δ): 7.52 (d, J = 13.0 Hz, 1H), 4.80 (d, J = 13.0 Hz, 1H),
3.88 (s, 3H), 3.02 (s, 6H).
(E)-2,2,7,7-Tetramethyl-3,6-dioxa-2,7-disilaoct-4-ene: 1H NMR
(300 MHz, p-xylene-d10, δ): 5.65 (s, 2H), 0.35 (s, 18H).
ACKNOWLEDGMENTS
■
We thank Zhuo Gao, Drs. Amlan Ray, Sabuj Kundu, and Ritu
Ahuja for generously providing samples of various catalysts.
We gratefully acknowledge support by the National Science
Foundation through grant CHE-1465203. The authors
acknowledge the Office of Advanced Research Computing at
Rutgers, The State University of New Jersey for providing
access to the Amarel cluster and associated research computing
resources.
5. COMPUTATIONAL METHODS
All calculations employed density functional theory (DFT)28 as
implemented in the GAUSSIAN 16 series of computer programs.29
We applied the M06 functional in the majority of calculations,30 along
with the SDD effective core potential and associated valence basis set
for the Ir atom;31 all other atoms (P, N, C, and H) were assigned all-
electron 6-31G(d,p) basis sets.32 Interactions with the bulk solvent
were simulated using the SMD dielectric continuum solvation
model33 and p-xylene as the model solvent. Normal mode analysis
was performed for stationary points, and thermal energy corrections
were evaluated using standard statistical mechanical expressions and
unscaled vibrational frequencies.34 Computed Gibbs free energies
were adjusted to a temperature of 50 °C for comparison with
experimental data.
REFERENCES
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ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.9b02846.
Computational details, tables of calculated energetic
quantities for full pathways, kinetic isotope effect
calculations, Cartesian coordinates of DFT optimiza-
tions, NMR spectra of unreported amines and reaction
mixtures, optimized structures (as .mol2 formatted files)
for all pathways considered (PDF)
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AUTHOR INFORMATION
■
Corresponding Author
Alan S. Goldman − Department of Chemistry and Chemical
Biology, Rutgers The State University of New Jersey, New
Brunswick, New Jersey 08903, United States; orcid.org/
0000-0002-2774-710X; Email: alan.goldman@rutgers.edu
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