Selective alkyl ether cleavage by cationic bis(phosphine)iridium complexes

Article abstract of DOI:10.1039/c8ob02298d

Catalysts capable of heterolytic silane activation have been successfully applied to the conversion of alkyl ethers to silyl ethers via C-O bond cleavage. The previously-reported cationic pincer-supported iridium complex for this transformation suffers fr

Full text of DOI:10.1039/c8ob02298d

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Selective alkyl ether cleavage by cationic
bis(phosphine)iridium complexes†
Cite this: DOI: 10.1039/c8ob02298d
Caleb A. H. Jones
and Nathan D. Schley
*
Received 17th September 2018,
Accepted 31st October 2018
DOI: 10.1039/c8ob02298d
rsc.li/obc
Catalysts capable of heterolytic silane activation have been suc- avenues for the development of systems with catalyst-con-
cessfully applied to the conversion of alkyl ethers to silyl ethers via trolled selectivity that would be applicable to complex mole-
C–O bond cleavage. The previously-reported cationic pincer-sup- cules. Promising classes of catalysts for this transformation
ported iridium complex for this transformation suffers from poor include electrophilic triaryl- and diarylboranes4–9 as well as a
selectivity with regard to monodealkylation of substrate ethers. We single example of a cationic iridium complex of a weakly-coor-
demonstrate that a simple non-pincer iridium complex offers dinating anion.10,11 In both cases the initial Si–O bond-
improved selectivity and is capable of benzylic ether cleavage in forming step is thought to proceed via Lewis acid-promoted
the presence of reductively-labile alkyl and aryl halide functional- silane activation to give a silyloxonium ion and an equivalent
ity. Preliminary mechanistic experiments suggest a neutral tetra- of the catalyst hydride.12
hydridosilyliridium resting state which is consistent with previous
To our knowledge the only iridium catalyst reported to
mechanistic hypotheses. These experiments suggest that a pincer cleave ethers via C–O single bond reduction with silanes is
ligand framework is not required for activity in ether cleavage reac- Brookhart’s cationic bis(phosphine)pincer iridium complex 1
tions and that simple cationic bis(phosphine)iridium complexes (Fig. 1, left).13 Related non-pincer complexes have been pre-
may offer improved selectivity profiles for applications to more- viously reported by Crabtree to effect dehydrosilylation of alco-
complex substrate molecules.
hols.14 Although the two transformations are distinct, both
implicate nucleophilic attack on an iridium σ-silane complex
in their respective Si–O bond-forming steps.
Our research group’s interest in reactions of alkyl ethers at
cationic bis(phosphine)iridium complexes has now led us to
explore catalytic ether cleavage via C–O silylation. In recent
work we demonstrated the stoichiometric C–O cleavage of
methyl tert-butyl ether by [(PPh3)2IrH2(THF)2]PF6.15 We now
Introduction
Primary and secondary alkyl ethers are robust organic func-
tional groups for which forcing conditions are typically required
to effect C–O cleavage. Traditional methods for ether cleavage
rely on their conversion to alkyl halides under the influence of
strong mineral acids1 or exhaustive hydrogenolysis to alkanes
over heterogeneous catalysts.2 Although well-developed and in-
expensive, these methods lack the intrinsic selectivity that
would be required for their application to complex polyether-
containing molecules including carbohydrate derivatives.3
In recent years a strategy for reductive ether cleavage
through catalytic silylation has emerged. These approaches
make use of catalyst-promoted silane Si–H heterolysis to gene-
rate electrophilic silyloxonium ions which are subject to sub-
sequent attack by hydride. The use of a catalyst opens up
show that the corresponding BArF (ArF = 3,5-bis(trifluoro-
4
methyl)phenyl) salt (2) is an active catalyst for the cleavage of
alkyl ethers with trialkyl silanes. In a key advance, we demon-
strate substantially improved selectivity over previous iridium
catalysts for this transformation and have applied this system
to a promising protecting group-interconversion process that
allows for debenzylation in the presence of reductively-labile
alkyl and aryl halides.
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, USA.
E-mail: nathan.schley@vanderbilt.edu
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
c8ob02298d
Fig. 1 Cationic iridium complexes of weakly coordinating anions.
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ditions tested, the BArF salt16 (2) rapidly cleaves a variety of
alkyl ethers with triethylsilane.
4
Results and discussion
At the outset of this study we identified a need for iridium cat-
Initial studies on a collection of unsymmetric ethers
alysts with improved selectivity profiles. Primary, secondary suggest that the reactivity of complex 2 depends strongly on
and tertiary ethers are rapidly cleaved by Brookhart’s POCOP the ether (Table 1). Benzyl ethers are highly reactive, undergoing
iridium catalyst (1) to give silyl ethers; however the resulting cleavage at the benzylic position in benzyl heptyl ether. Benzyl
silyl ether products are subject to subsequent reduction to the cyclohexyl ether is also cleaved at the benzylic position, but
alkanes (Scheme 1, top). This reactivity was employed to great requires an elevated catalyst loading of 3% (Table 1, entry 2).
effect by Gagné in a recent report detailing the exhaustive Primary methyl ethers undergo demethylation while secondary
deoxygenation of glucose to hexanes,11 but is also a sign of a methyl ethers are cleaved at the 2° position. Primary
lack of intrinsic selectivity that limits applications in the syn- secondary ethers show poor reactivity, even with long reaction
thesis of functionalized molecules.
times and high catalyst loading. In nearly all cases the resulting
The mechanistic similarity between ether silylation and silyl ethers appear to be stable with respect to further reduction.17
alcohol dehydrosilylation encouraged us to explore non-pincer Although complex 2 is able to cleave MTBE, other tertiary ethers
bis(phosphine)iridium complexes for reductive ether cleavage including t-butyl benzyl ether were not reduced (Table 2, entries 6
catalysis. Our hypothesis was that these complexes would also and 7). Surprisingly, benzylic ether cleavage could be accom-
serve as catalysts for ether cleavage, and would provide a plished selectively even in the presence of a methyl ether
tunable platform for 2nd generation catalyst development (Table 1, entry 8). These preliminary observations on the reactivity
through the preparation of variants of commercially available of complex 2 show significantly attenuated reactivity versus
monophosphines.
Although
the
hexafluorophosphate Brookhart’s complex 1, validating our hypothesis that more-selec-
complex15 [(PPh3)2IrH2(THF)2]PF6 is inactive under the con- tive iridium catalysts could be obtained through the use of cat-
ionic non-pincer bis(phosphine)iridium complexes.
The rapid and selective cleavage of benzyl ethers suggested
that complex 2 could potentially serve as a catalyst for the con-
version of benzylic ethers to silyl ethers. Benzylic ethers are
typically cleaved by hydrogenolysis under mild conditions with
heterogeneous metal catalysts. The ease of benzylic ether for-
mation and subsequent deprotection has led to applications of
benzyl ethers as versatile protecting groups for alcohols.18
Benzyl ether hydrogenolysis over heterogeneous Pd catalysts is
compatible with an array of functional groups, but alkenes,
alkynes and azides undergo reduction, while alkyl and aryl
halides and psuedohalides are also subject to competitive
Scheme 1 Exhaustive ether cleavage by 1.
hydrodehalogenation or catalyst poisoning under certain
conditions.19–22
Table 1 Cleavage of unsymmetrical ethers by 2
Entry
Substrate
Conditions
1 mol% 1 h
3 mol% 2 h
Silyl ether
NMR yield
>98%
1
2
70%
3
4
1 mol% 8 h
1 mol% 2 h
75%
61%
CH3OSiEt3
5
3 mol% 48 h
26%
6
7
1 mol% 48 h
1 mol% 48 h
NR
NR
—
—
8
3 mol% 40 min
>98%
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Under our optimized conditions, a variety of alkyl and aryl
halides are tolerated (Fig. 2). Benzylic ether cleavage is
observed without reduction of an aryl chloride, bromide or
iodide. An aryl triflate is similarly untouched under our con-
ditions. Although primary alkyl chlorides, bromides, and
iodides all survive benzyl ether silylation in moderate to good
yield, somewhat lower yields are obtained for a substrate con-
ð2Þ
A proposed mechanism for ether cleavage catalyzed by 2 is
taining a secondary alkyl bromide. In contrast to our results given in Scheme 2.13 An interesting feature of iridium-cata-
with 2, complex 1 is a reported hydrodehalogenation catalyst lyzed ether silylation is its resemblance to the borane-catalyzed
under closely-related conditions.23
reaction.27 The key mechanistic similarity between both
In line with the reported dehydrosilylation activity of related iridium and borane-catalyzed ether silylation is the heterolytic
complexes, substrates containing free alcohols undergo dehy- cleavage of the silane to give a silyloxonium ion and a metal
drosilylation more rapidly than ether cleavage. We have been hydride or borohydride respectively. When the reduction of
able to exploit this property in the selective disilylation of 3- benzyl heptyl ether by 2 is monitored by 31P{1H} NMR, a single
(benzyloxy)propanol (eqn (1)). Sequential treatment with tert- major resonance appears at 13.7 ppm. We have found that the
butyl(dimethyl)silane (1.1 equiv.) and diethyl(methyl)silane (2.2 same species can be generated by treatment of the neutral
equiv.) gives the unsymmetrically silylated 1,3-propanediol.
iridium pentahydride (PPh3)2IrH5 (3) with Et3SiH, indicating
that the major iridium-containing species during the reaction
is a neutral complex lacking the BArF4 anion. This complex has
been previously characterized as the neutral iridium tetra-
hydrido silyl complex 4 (eqn (2)).28 Formation of 4 during cata-
lysis likely occurs via attack of an ether on a σ-Si–H complex13
to give (PPh3)2IrH3 (5) followed by oxidative addition of a
second equivalent of Et3SiH (Scheme 2). The presence of 4 as
the major iridium-containing species during catalysis is com-
patible with the general framework for the overall mechanism
proposed by Brookhart13 and well as studies on a related cata-
lytic reaction by Oestrich.12
In both iridium and borane-catalyzed varients of this trans-
formation, hydride attack on the dialkysilyloxonium ion is pro-
posed to be responsible for the C–O bond cleavage step.
Brookhart has proposed that a neutral iridium(III)dihydride
resulting from silylium transfer to the ether may be respon-
sible for this step.13 Studies on a closely related system by
Oestreich have also implicated a neutral iridium(V)silyltri-
hydride or iridium(III)dihydrido σ-silane, though recent calcu-
lations appear to support the hypothesis that the iridium(III)
dihydride is competent for ether cleavage.29 Our observation of
ð1Þ
A survey of the scope of compatible functionality with our
silyl ether cleavage conditions also revealed some limitations.
As many iridium complexes including 1 are excellent hydro-
silylation catalysts for olefins and carbonyl derivatives,24,25
substrates containing such functionality were not suitable for
ether cleavage by 2. Similarly, substrates containing Lewis
basic functionality including nitriles, amines, thioethers, and
azides are totally unreactive under our optimized conditions.
Thus substrates which are either more Lewis-basic than ethers
or are known to undergo rapid hydrosilylation appear to pose
a challenge for this system.26 We suspect further catalyst devel-
opment may provide solutions for certain substrate classes,
but given the kinetic stability of ethers relative to other func-
tionality, these limitations are unsurprising.
complex
4 during catalysis is wholly consistent with
Oestreich’s mechanistic proposal and allows us to tentatively
suggest that complex 4 may be responsible for hydride transfer
to the silyloxonium ion. Importantly, complex 4 itself does not
serve as a catalyst for ether silylation when generated in situ
from 3 (eqn (3)). This observation suggests that a cationic pre-
cursor is required for silyloxonium ion formation. On the
other hand, complex 4 is extremely active when applied in the
presence of equimolar [CPh3]BArF (eqn (4)). For this experi-
4
ment, [CPh3]BArF4 was added to a benzene solution of triethyl-
silane to generate a known triethylsilylium ion equivalent30
which was then treated with substrate ether to give the silyloxo-
nium ion. Subsequent addition of a solution of 4 leads to
rapid catalysis (eqn (4)). Alternatively, [CPh3]BArF4 or a triethyl-
silylium ion generated in situ may serve to abstract a hydride
from 4 to give a cationic iridium species related to 2. Indeed
treatment of a THF solution of 4 with [CPh3]BArF appears to
4
Fig. 2 Isolated yields obtained in the conversion of benzyl ethers to
silyl ethers by 2.
give 2 by 31P NMR. In either case, complex 4 alone is clearly
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Table 2 Comparison of catalysis by 2 versus the borane BArF
3
Entry
Catalyst
Solvent
Time
NMR yield
1
2
3
4
5
BArF
C6D6
2 h
<1%
>98%
9%
39%
85%
3
Complex 2
CD2Cl2
CD2Cl2
CD2Cl2
CD2Cl2
15 m
15 m
1 h
BArF
BArF3
BArF3
4 h
3
Scheme 2 Proposed mechanism for ether cleavage by 2.
ð6Þ
insufficiently electrophilic to transfer an equivalent of triethyl-
silylium to substrate ether.
Conclusions
ð3Þ
ð4Þ
We have demonstrated that a simple cationic non-pincer
bis(phosphine)iridium complex is an active catalyst for the
conversion of alkyl ethers into silyl ethers. [(PPh3)2IrH2(THF)2]
BArF4 is significantly more selective than the previous reported
iridium system for the same transformation, and is able to
cleave benzylic ethers in the presence of sensitive alkyl and
aryl halide functionality. Unlike the previous pincer-supported
system, the product silyl ethers are not subject to complete
deoxygenation. Preliminary mechanistic experiments strongly
The efficacy of borane catalysts with structurally similar
motifs to the weakly coordinating anions used in this study
warrants discussion. B–C cleavage might be expected to gene-
suggest that [(PPh3)2IrH2(THF)2]BArF operates according to
4
the accepted mechanism for iridium- and borane-catalyzed
ether silylation reactions. Our findings suggest that cationic
bis(phosphine)iridium complexes may be a promising catalyst
platform for the development of more-selective C–O bond
cleavage reactions of functionalized molecules.
rate the triaryl borane BArF [tris(3,5-bis(trifluoromethyl)
3
phenyl)borane]. The similarity of BArF to tris(pentafluorophe-
3
nyl)borane (BCF), a known catalyst for ether hydrosilylation
led us to investigate the possibility that anion degradation to
an active catalyst could be responsible for our observed reactiv-
ity. Under our catalytic conditions the BArF anion remains
4
unchanged by 19F-NMR spectroscopy which precludes the for-
Conflicts of interest
mation of BArF at concentrations detectable with this tech-
3
There are no conflicts to declare.
nique. Furthermore, NaBArF is inactive for ether cleavage
4
both on its own and in the presence of the neutral tetrahydri-
dosilyliridium complex 4. Finally, we independently prepared
Acknowledgements
the BArF borane and compared its reactivity to reactions cata-
3
lyzed by 2. BArF is a poor catalyst for ether reduction under
3
Acknowledgment is made to the Donors of the American
Chemical Society Petroleum Research Fund for partial support
of this research. Funding from Vanderbilt University is grate-
fully acknowledged.
our optimized conditions (Table 2, entry 1), and while it
improves in CD2Cl2 solvent, catalysis by BArF is significantly
3
slower than catalysis by 2. For instance, after 15 minutes we
see complete conversion using 2 (>30 turnovers) and only 3
turnovers when BArF is used as the catalyst over the same
3
time period. Therefore these results allow us to rule out the
possibility that the observed catalytic behavior of 2 results from
trace borane generated by anion degradation. In a related experi-
ment we found that catalysis by 2 is not inhibited by the pres-
ence of excess Hg metal, providing evidence against degradation
of 2 to active iridium(0) nanoparticles in situ (eqn (6)).31,32
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