Phosphine-imine and-enamido ligands for acceptorless dehydrogenation catalysis

Article abstract of DOI:10.1039/c6dt04088h

A highly tunable phosphine-imine ligand family is introduced. Following metallation with ruthenium, deprotonation of the ligand affords a phosphine-enamido species. Complexes with the ligand in both the imine and enamido forms are active toward acceptorless dehydrogenation reactions.

Full text of DOI:10.1039/c6dt04088h

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Phosphine–imine and –enamido ligands for
acceptorless dehydrogenation catalysis†
Cite this: DOI: 10.1039/c6dt04088h
Received 24th October 2016,
Accepted 22nd November 2016
J. M. Stubbs,‡ K. F. Firth,‡ B. J. Bridge, K. J. Berger, R. J. Hazlehurst, P. D. Boyle and
J. M. Blacquiere*
DOI: 10.1039/c6dt04088h
www.rsc.org/dalton
A highly tunable phosphine–imine ligand family is introduced. phosphine–enamido catalysts is limited, thus improvements
Following metallation with ruthenium, deprotonation of the ligand in catalyst design are warranted. We report here a new ligand
affords a phosphine–enamido species. Complexes with the ligand family that contains phosphine and imine moieties, and
in both the imine and enamido forms are active toward acceptor- deprotonation gives a phosphine–enamido species. Catalytic
less dehydrogenation reactions.
performance of complexes with the ligand in both enamido
and imine forms is evaluated.
Metal–ligand cooperative (MLC) catalysts1–3 give chiral alco-
hols and amines by hydrogenation,4,5 and carboxylic acids,
esters, amides and imines by acceptorless dehydrogenation
reactions.6,7 These catalysts contain an acid/base site on the
ligand that shuttles protons to or from the metal active site. In
the highly successful Milstein-type catalysts (Fig. 1), the
driving force for protonation is ligand aromatization to give a
central pyridyl moiety.7–14 However, aromatization is not essen-
tial since acceptorless dehydrogenation is achieved with phos-
phine–enamido complexes that give non-aromatic imine moi-
eties on ligand protonation.15–17 H2 activation reactions
confirm that a cooperative pathway is accessible. Since rela-
tively few phosphine–enamido catalysts have been studied, the
extent to which non-aromatic systems follow cooperative path-
ways is unknown. Additionally, the performance of the known
The phosphine–imine pro-ligand, H(1) was obtained on
condensation of 2-diphenylphosphinoaniline with isobutyr-
aldehyde (Scheme 1). Formation of H(1) is evident from a
ca. 5 ppm downfield shift of the 31P resonance relative to the
starting material. The alpha-imine proton (H1; see Scheme 1
for label assignments) is found at 7.29 ppm as confirmed
by a 1H–1H COSY NMR correlation to the unique isopropyl
proton (H2).
Treatment of RuCl2(PPh3)3 with H(1) in THF results in a
colour change from purple to green (Scheme 1), consistent
with a switch to a weaker-field donor (i.e. PPh3 to imine).
Isolation and analysis by 31P{1H} NMR spectroscopy revealed a
set of two doublets at δP 89.0 and 46.0 for the phosphine
atoms of H(1) and PPh3 ligands, respectively. The coupling
constant (2JPP
= 35 Hz) indicates a
cis disposition.18
Crystallization from DMF gives an octahedral solvent adduct
Fig. 1 Cooperative H2 formation and activation with a general Milstein
pincer catalyst, showing aromatic pyridyl and dearomatized enamido
species.
Department of Chemistry, University of Western Ontario, London, Ontario, N6A 5B7,
Canada. E-mail: johanna.blacquiere@uwo.ca
†Electronic supplementary information (ESI) available: General, synthetic and
catalytic procedures; IR and NMR spectra; GC-FID calibration and catalysis
curves; crystallographic information. CCDC 1470534 and 1470535. For ESI and
crystallographic data in CIF or other electronic format see DOI: 10.1039/
c6dt04088h
Scheme 1 Synthesis of ligand H(1), and Ru complexes
2 and 3.
Reaction conditions: (i) equiv. isobutyraldehyde, 5% formic acid,
2
toluene, RT, 24 h, 72% yield; (ii) RuCl2(PPh3)3, THF, RT, 2 h, 70% yield. (iii)
1.15 equiv. Li[N(SiMe3)2], pyridine, RT, 2 h, 85% yield (95% purity).
‡These authors contributed equally to this work.
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Table 1 Catalyst comparison and optimization for AD of BnOH with
2 and 3a
Entry
[Ru] (mol%)
Additive
Conv. (%)
%A
%B
1
2
3
4
5
6
7
3 (0.1)
3 (1)
3 (5)
2 (5)
2 (5)
2 (5)
2 (5)
—
—
—
—
3
34
49
7
54
17
59
3
33
46
3
27
12
44
0
0
1
0
2
0
1
b
KPF6
Pyc + KPF6
b
Li[N(SiMe3)2]b
Fig. 2 Displacement ellipsoid diagrams of (a) 2 as a DMF solvate (CCDC
1470534); and (b) 3 (CCDC 1470535). Ellipsoids are shown at 50% prob-
ability and hydrogen atoms are removed for clarity. Selected bond
lengths for: 2 = Ru–P1 2.2403(10), Ru–N1 2.087(2), N1–C1 1.285(4), C1–
C2 1.396(5); 3 = Ru–P1 2.2406(14), Ru–N1 2.091(4), N1–C1 1.400(6),
C1–C2 1.332(7).
a Conditions: (i) BnOH (250 mM), tetralin (120 mM), toluene (0.5 mL),
100 °C, 48 h. Substrate conv. and product yields were determined by
analysis of reaction samples (diluted to 20 mM) by calibrated GC-FID,
values are an average of 2 or 3 runs and errors are < 5%. b 5 mol%
relative to BnOH. c 15 mol% relative to BnOH.
imine form it cannot mediate a concerted MLC dehydrogena-
tion of BnOH. Likely, 2 operates via a non-MLC mechanism
and this raises the possibility that 3 may also follow a non-
MLC pathway. In addition to KPF6, pyridine was added to 2 to
more closely mimic the ancillary ligands of 3 (entry 6). Poor
turnover was observed suggesting the added pyridine inhibits
substrate binding to the catalyst. In situ treatment of 2 with Li
[N(SiMe3)2] likely gives a species analogous to 2/KPF6, except
the ligand is deprotonated to the phosphine–enamido form.
This is supported by the similar performance of 2/Li
[N(SiMe3)2] and the isolated phosphine–enamido complex 3
(entry 7). Monitoring the three best catalysts (3; 2/KPF6; 2/Li
[N(SiMe3)2]) over time revealed that maximum conversion is
reached within 24 h and no obvious induction period is
observed (ESI†).
Acceptorless dehydrogenative coupling (ADC) of BnOH with
benzyl amine (BnNH2; Scheme 3) is known to give different
products depending on the nature of the catalyst.21,22 AD of
BnOH gives aldehyde A, which undergoes coupling with
BnNH2 to give imine C with release of H2O. Rehydrogenation
of the imine gives amine D via a hydrogen-borrowing pathway.
Alternatively, imine C can be formed through dehydrogenation
of BnNH2 and coupling with a second amine equivalent.23,24
Or a double AD of BnNH2 gives nitrile E.25–27 The intermediate
hemiaminal on route to C (from ACD of BnOH with BnNH2)
can undergo a second AD to give amide F. ADC of BnOH and
BnNH2 was assessed with 5 mol% of the three catalysts: 3, 2/Li
[N(SiMe3)2] and 2/KPF6 (Table 2). Catalyst 3 consumed all of
the starting amine and nearly half of the alcohol (Table 2,
entry 1) to give a mixture of aldehyde (A), imine (C) and nitrile
(Fig. 2a) where the N–C1 bond length of 1.285(4) Å is in the
expected range for an imine moiety.
Addition of pyridine to 2 resulted in an immediate colour
change from green to amber (presumably due to the 6-coordi-
nate solvate) and a change to red occurred on addition of one
equivalent of the base Li[N(SiMe3)2] (Scheme 1). X-ray diffrac-
tion of the octahedral product 3 shows ligand 1 is bound in a
bidentate κ2-PN fashion (Fig. 2b). Deprotonation to give an
enamido is indicated by an increase of the N–C1 bond length
by 0.12 Å and a decrease in the C1–C2 distance by 0.06 Å versus
the imine complex 2. The planarity about C2 in 3 further con-
firms the sp2 nature of this centre. In the solution state, 3 is
characterized by a singlet in the 31P{1H} NMR spectrum at δ
71.6, ca. 17 ppm upfield of the analogous signal in 2. The
signal for C2 (δC 118.8) is shifted 82 ppm downfield relative to
2,
a location diagnostic for a
κ1-N enamido.16,17,19,20
Deprotonation is accompanied by halide abstraction of one
chloride ligand, giving LiCl as a byproduct, and pyridine
occupies the vacated coordination site.
Acceptorless dehydrogenation (AD) of benzyl alcohol
(BnOH; Scheme 2) can directly give benzaldehyde (A) or an
ester (B), which is formed via nucleophilic attack of A by
additional alcohol, followed by
a
second AD step.21
Dehydrogenation of BnOH with 3 (1 mol%) over 48 h gave A as
the sole product in 33% yield (Table 1, entry 2). Increasing the
catalyst loading gives marginal improvement with a 46% yield
(entry 3). Under the same conditions, phosphine–imine
complex 2 gave only minimal (7%) conversion (entry 4).
Surprisingly, 54% conversion is achieved on halide-abstraction
from 2 with KPF6 (entry 5). Aldehyde A is the major product,
but mass balance is not achieved indicating a side reaction
does occur. Since the ligand in 2 is already in the protonated
Scheme 2 Acceptorless dehydrogenation (AD) of benzyl alcohol
(BnOH) to give aldehyde (A) or ester (B) products.
Scheme 3 Possible products from acceptorless dehydrogenative coup-
ling (ADC) of BnOH and BnNH2.
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a
Table 2 Catalyst performance in the dehydrogenation of BnOH and/or BnNH2
Conv.b (%)
Yieldb (%)
Entry
[Ru]
Additive
BnOH
BnNH2
A
C
D
E
F
1
2
3
4
5
6
3
2
2
3
2
2
—
40
32
76
—
—
—
100
96
86
87
91
98
10
1
24
—
—
—
31
29
12
46
25
57
0
1
3
0
0
0
20
34
26
41
33
35
0
0
0
—
—
—
Li[N(SiMe3)2]c
c
KPF6
—
Li[N(SiMe3)2]c
c
KPF6
a Conditions: (i) BnOH (250 mM), BnNH2 (250 mM), tetralin (120 mM), 5 mol% [Ru], toluene (0.5 mL), 100 °C, 48 h. b Substrate consumption and
product yields were determined by analysis of reaction samples (diluted to 20 mM) by calibrated GC-FID, values are an average of 2 or 3 runs and
errors are < 5%. c 1 equiv. relative to 2.
(E) in a 1 : 3 : 2 ratio. The consumption values and prevalence tial reaction with amines over alcohols. Phosphine–imine 2 is
of C and E suggests that AD of BnNH2 competes with that of inactive, but halide abstraction or ligand deprotonation both
BnOH. This is contrary to nearly all reported catalysts for this give an active catalyst, which likely operates through a non-
reaction that favour reaction with alcohol over amine. Only one cooperative mechanism. The synthetic accessibility of the
reported system preferentially dehydrogenates amines over ligand in both imine and enamido forms suggests cooperative
alcohols.23 This feature of catalyst 3 could be exploited proton shuttling is feasible without ligand aromatization as a
through future ligand derivatives that may further improve driving force. However, the catalytic competency of the phos-
selectivity. In situ generation of the phosphine–enamido cata- phine–imine complex raises the possibility that, non-coopera-
lyst (2/Li[N(SiMe3)2]) gives a very similar selectivity profile to 3 tive mechanisms may be operative and they will be considered
(entry 2). On the other hand, the phosphine–imine catalyst in due course.
(2/KPF6; entry 3) consumes nearly equal amounts of BnOH and
BnNH2 to give A, C and E in a 2 : 1 : 2 ratio. While the limited
selectivity of the catalysts precludes application to other sub-
strates, the product distribution provides some insight into
the catalyst performance. Notably, the distinct selectivity
between the phosphine–imine catalyst and the phosphine–
enamido catalysts suggests different dehydrogenation path-
ways are dominant when the ligand is in the protonated or
deprotonated forms.
All three catalysts give nearly quantitative conversion
toward the dehydrogenation of benzylamine to give imine (C)
or nitrile (E) (Table 2, entries 4–6). Phosphine–enamido 3 gives
a 1 : 1 mixture of the two products while phosphine–imine 2
gives the imine as the preferred product in nearly a 2 : 1 ratio.
None of the catalysts are capable of the hydrogen borrowing
reaction, despite that these reactions were conducted in sealed
containers, suggesting H2 release (whether through an MLC or
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