Air- And Water-Tolerant (PNP)Ir Precatalyst for the Dehydrogenative Borylation of Terminal Alkynes

Article abstract of DOI:10.1021/acs.organomet.0c00250

This work discloses the facile synthesis and efficacy of (PNP)IrH(OAc), a precatalyst for the dehydrogenative borylation of terminal alkynes (DHBTA). Unlike the previously reported precatalysts in the (PNP)Ir system (PNP = diarylamido/bis(phosphine) pincer), it is air-stable in the solid state. Upon exposure to air in solution, it possesses a useful half-life on the order of 1-100 h, depending on the intensity of mixing. Air-degraded solutions of (PNP)IrH(OAc) retain DHBTA catalytic activity and selectivity upon exposure to the mixture of a terminal alkyne and HBpin. It is also demonstrated that (PNP)Ir-catalyzed DHBTA is compatible with the presence of modest amounts of moisture or air and that the catalyst is sufficiently long-lived to deliver turnover numbers (TONs) of > 100 ?000.

Full text of DOI:10.1021/acs.organomet.0c00250

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Air- and Water-Tolerant (PNP)Ir Precatalyst for the Dehydrogenative
Borylation of Terminal Alkynes
Bryan J. Foley and Oleg V. Ozerov*
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ABSTRACT: This work discloses the facile synthesis and efficacy
of (PNP)IrH(OAc), a precatalyst for the dehydrogenative
borylation of terminal alkynes (DHBTA). Unlike the previously
reported precatalysts in the (PNP)Ir system (PNP = diarylamido/
bis(phosphine) pincer), it is air-stable in the solid state. Upon
exposure to air in solution, it possesses a useful half-life on the
order of 1−100 h, depending on the intensity of mixing. Air-
degraded solutions of (PNP)IrH(OAc) retain DHBTA catalytic
activity and selectivity upon exposure to the mixture of a terminal
alkyne and HBpin. It is also demonstrated that (PNP)Ir-catalyzed
DHBTA is compatible with the presence of modest amounts of moisture or air and that the catalyst is sufficiently long-lived to
deliver turnover numbers (TONs) of > 100 000.
Scheme 1. Definition of Dehydrogenative Borylation of
Terminal Alkynes (DHBTA) and the Various DHBTA
Catalysts from the Literature
−H borylation is a powerful method for the function-
alization of various C−H bonds.1−4 The products of C−
C
H borylation are typically organoboronates or other derivatives
of organoboronic acids. Organoboronates are valuable
synthetic intermediates that permit the construction of new
carbon−carbon and carbon−heteroatom bonds.5 Some of the
most impressive successes in C−H borylation are associated
with Ir-catalyzed C−H borylation of aromatic C(sp2)−H
bonds.6−8
Our group has been interested in dehydrogenative
borylation of terminal alkynes (DHBTA) (Scheme 1). The
products of DHBTA are alkynylboronates, which can be used
in a variety of synthetic transformations.9 We originally
reported that an Ir catalyst supported by a SiNN-type pincer
ligand was highly chemoselective and gave rise only to
DHBTA products with turnover numbers (TONs) of about
100 with a variety of alkynes, but largely excluding those with
propargyl−heteroatom connections.10 We later explored a
variety of other pincers as supporting ligands for Ir in DHBTA
and discovered that the diarylamido-based PNP ligands
perform very well in that role.11 Several different PNP ligands
have been studied.11 It was shown that these are highly long-
lived catalysts, capable of thousands of turnovers with a variety
of alkynes, now including propargyl-substituted ones. The
mechanism of DHBTA catalysis by the SiNN- and PNP-
supported Ir complexes has been thoroughly investigated
computationally and experimentally.12,13 Other groups re-
ported DHBTA catalysts based on Zn,14,15 Cu,16 and Fe,17 and
we reported a Pd-based DHBTA catalyst (Scheme 1).18 Chirik
et al. also reported a Co catalyst that produces alkynylboro-
nates from terminal alkynes en route to 1,1-diborated alkene
products.19 These are interesting examples, especially in the
Received: April 9, 2020
https://dx.doi.org/10.1021/acs.organomet.0c00250
© XXXX American Chemical Society
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A

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Communication
sense of the remarkable diversity of the nature of possible
DHBTA catalysts. However, they do not rival the (PNP)Ir
system11 in terms of activity and longevity, nor do they offer an
expanded alkyne substrate scope.
kept in a cabinet in the laboratory under air (Figure S3).
Periodically, a sample was removed and brought back into an
argon-filled glovebox, where the solids were dissolved in
anhydrous, deoxygenated C6D6 for NMR spectroscopic
analysis. Even after 110 days, no degradation of the iridium
complex could be detected (Figure S4). Exposing a standing
benzene solution of (PNP)IrH(OAc) in an NMR tube to air
for 5 days resulted in the decomposition of only ∼45% of the
complex (NMR evidence, Figure S1). However, stirring a
solution of (PNP)IrH(OAc) open to air resulted in complete
decomposition in 3 h (Figure S2). Thus, (PNP)IrH(OAc) is
fully resistant to air as a solid on the scale of at least months
but is degraded in solution at a rate concomitant with the
degree of agitation.
The downside of (PNP)Ir-catalyzed DHBTA is that all of
the precatalysts used to date have been air-sensitive
compounds, requiring the DHBTA reactions to be carried
out under an inert atmosphere in dry, deoxygenated solvents.11
However, we surmised that it should be possible to design a
(PNP)Ir precatalyst that would possess some air stability while
being capable of effective initiation of DHBTA. We also
surmised that even if the Ir precursor is converted to some new
Ir−O containing “decomposition” products upon interaction
with air and/or moisture, they might be converted back to the
active species in the DHBTA mixture by the action of the
excess of HBpin present. In this we were influenced by the
existing work on the reactions of Ir pincer complexes with
O2.20−22 Lastly, we wondered whether the presence of water
might not be inhibitory to DHBTA but rather simply serve as
an undesirable but catalytically benign sink for some of the
HBpin reagent. The present work reports our findings that
these conjectures had merit and that an effective air- and
moisture-tolerant DHBTA catalyst is indeed possible.
We hypothesized that a saturated 18-electron (PNP)Ir
complex might possess useful stability toward air and moisture.
We zeroed in on (PNP)IrH(OAc) as a promising candidate
that should be easily converted into DHBTA-relevant species
upon reaction with excess HBpin in a catalytic DHBTA
mixture. Combining (PNP)H, [(COD)IrCl]2, and NaOAc·
3H2O in a vial with fluorobenzene and stirring for 4 h resulted
in a red-orange solution. Recrystallization from pentane
afforded (PNP)IrH(OAc) cleanly as a dusty orange powder
in 84% yield (Scheme 2). The same product was also obtained
The effectiveness of (PNP)IrH(OAc) as a DHBTA
precatalyst was tested in the catalysis of the reaction of 4-
MeC6H4CCH with HBpin (Table 1). The rate at which
a
Table 1. Performance of (PNP)IrH(OAc) with Selected
Substrates
b
entry
alkyne
time
conv. (%)
yield (%)
c
1
2
3
4
5
6
7
8
9
10
11
12
13
4-MeC6H4CCH
10 min
30 min
20 h
10 min
50 min
20 h
10 min
55 min
19 h
10 min
60 min
19 h
46
61
100
24
57
100
43
72
100
14
30
80
41/3
56/5
92/8
24
57
100
38/5
64/8
c
c
Me2NCH2CCH
Me3SiOCH2CCH
n-C8H17CCH
d
d
d
86/14
14
30
80
100
72 h
100
Scheme 2. Synthesis of (PNP)IrH(OAc) and Aging
Experiments
a
b
0.29 μmol (0.84 mol %) catalyst loading. Percent conversion
1
measured by H NMR spectroscopy using 1,4-dioxane as an internal
c
standard. DHBTA product/hydrogenated alkyne (4-ethyltoluene).
d
DHBTA product/hydrogenated alkyne (trimethylsiloxypropane).
(PNP)IrH(OAc) performs was found to be indistinguishable
from the rate of DHBTA with (PNP)IrH2 as the precatalyst
(Scheme 3). Moreover, observation of the hydride region of
1
the H NMR spectrum during a DHBTA reaction initiated by
(PNP)IrH(OAc) revealed the presence of only two hydride
resonances (at −5.35 and −12.40 ppm, 1:2 ratio) correspond-
ing to (PNP)IrH3Bpin (Scheme 3 and Figures S9 and S12).
This indicates that under DHBTA conditions the same resting
state is reached starting from (PNP)IrH2 or (PNP)IrH(OAc).
(PNP)IrH(OAc) was further used as a precatalyst for the
DHBTA of 3-dimethylamino-1-propyne, 3-trimethylsiloxy-1-
propyne, and 1-decyne (Table 1). Clean borylation of 3-
dimethylamino-1-propyne and 1-decyne were achieved. The
apparent rates of these were very similar to those catalyzed by
(PNP)IrH2. In the borylations of 3-trimethylsiloxy-1-propyne
and p-MeC6H4CCH, the ratios of the DHBTA product to
hydrogenated side product were very similar to the ratios
observed with (PNP)IrH2 as a precatalyt.11
by treatment of a toluene solution of (PNP)H with a slight
deficiency of [(COD)Ir(OAc)]n. (PNP)IrH(OAc) displayed
NMR spectroscopic features consistent with a Cs-symmetric
1
PNP complex. The H NMR hydride chemical shift near −34
ppm is indicative of a hydride trans to a weakly trans-
influencing oxygen donor of a κ2-acetate. The κ2-carboxylate
binding motif is common in pincer complexes of Ir(III).23,24
The resistance of (PNP)IrH(OAc) to aerobic decom-
position was tested in the solid state and in solution. A series of
open vials containing solid samples of (PNP)IrH(OAc) were
Interestingly, a solution of fully aerobically degraded
(PNP)IrH(OAc) was also capable of performing DHBTA
(Figures S8 and S9). This implies that the mixture of the
presumed25 oxygenated iridium species can be revived by
HBpin and reenter the catalytic cycle.
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Communication
the alkyne to 4-MeC6H4CCBpin and 4-ethyltoluene
(Figures S10 and S11). These results strongly suggest that a
reaction with water consumes some of the HBpin reagent to
make (Bpin)2O but is not otherwise detrimental to the
DHBTA catalysis.26 We further determined that 4-
MeC6H4CCBpin is reasonably stable toward aerobic
degradation, as after 22 h of exposure to air both as a solid
and in a standing solution, less than 10% of the product had
Scheme 3. Use of (PNP)IrH(OAc) in DHBTA and the
Resting State Observed in the Reactions with p-MeC6H4C
CH and Me2NCH2CCH
1
degraded as observed by H NMR spectroscopy (Figures S5
and S6).
Next, we performed a preparative-scale DHBTA experiment
in toluene solvent (HPLC grade) that had not been dried after
purchase. The toluene solution of HBpin and 4-ethynyltoluene
was sparged with nitrogen prior to the addition of (PNP)-
IrH(OAc), and nitrogen continued to be bubbled through the
mixture during the reaction (see page S20 in the Supporting
Information). After 90 min, the volatiles were removed, and
the flask was taken into an Ar-filled glovebox. 1H NMR
spectroscopic analysis revealed the presence of (Bpin)2O in
addition to the desired 4-Me-C6H4CCBpin. Recrystalliza-
tion from pentane yielded 4-MeC6H4CCBpin with >97%
purity in 84% yield. This experiment confirmed that the
presence of some water is not fatal to DHBTA and that
dinitrogen is not detrimental to the reaction.27,28
To evaluate whether an inert atmosphere is at all necessary
for DHBTA, we carried out an experiment that was fully
constituted in air. A vial was loaded with HBpin, 4-
MeC6H4CCH, and 0.75 mol % (PNP)IrH(OAc) in C6D6
(which was used as received) and then sealed. It was
periodically agitated by hand and vented to relieve excess
pressure over the course of 90 min. After 90 min, the reaction
mixture was analyzed by NMR spectroscopy, and complete
conversion of 4-MeC6H4CCH to 4-MeC6H4CCBpin and
4-ethyltoluene in a 93:7 ratio was noted (Figure S12).
In summary, it has been demonstrated that PNP-supported
Ir catalysis of DHBTA is generally tolerant of the presence of
water and air in the reaction mixture, provided that a sufficient
excess of HBpin is utilized to consume H2O and O2
stoichiometrically. The catalysis is also compatible with
dinitrogen. (PNP)IrH(OAc) is an effective and convenient
DHBTA precatalyst that is stable toward air in the solid state
for months and in solution for up to hours or days, depending
on the degree of mixing. Moreover, its degradation under air
appears to be reversible by the action of excess HBpin in the
catalytic mixture.
In an experiment meant to push the limits of catalytic
turnover, 200 pmol of (PNP)IrH(OAc) was added to a 200
μmol sample of 3-dimethylamino-1-propyne and HBpin
(under argon, in dry C6D6). After ca. 3 months at 80 °C,
>100 000 turnovers were recorded in an ongoing reaction
(Figure S7)! While this exact setup is probably not a practical
protocol, it illustrates the very high longevity of the catalyst.
To test the sensitivity of DHBTA to water, two DHBTA
reactions were conducted under dry argon (Scheme 4). Each
was carried out with 1 equiv of water per alkyne, but the first
contained 2 equiv of HBpin and the second contained 4 equiv
(also per alkyne). The first reaction resulted in the
consumption of only half of the alkyne, yet all of the HBpin
was consumed. The second afforded complete conversion of
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.organomet.0c00250.
Scheme 4. DHBTA in the Presence of 1 equiv of H2O and
Various Amounts of HBpin
Details of experimental procedures and spectroscopic
characterization (PDF)
Time-lapse video of a 30 mM solution of (PNP)IrH-
(OAc) in C6D6 stirring open to air for 30 minutes (AVI)
AUTHOR INFORMATION
■
Corresponding Author
Oleg V. Ozerov − Department of Chemistry, Texas A&M
University, College Station, Texas 77842, United States;
orcid.org/0000-0002-5627-1120; Email: ozerov@
chem.tamu.edu
C
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(17) Wei, D.; Carboni, B.; Sortais, J.-B.; Darcel, C. Iron-catalyzed
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Author
Bryan J. Foley − Department of Chemistry, Texas A&M
University, College Station, Texas 77842, United States;
orcid.org/0000-0003-0570-769X
(18) Pell, C. J.; Ozerov, O. V. Catalytic dehydrogenative borylation
of terminal alkynes by POCOP-supported palladium complexes. Inorg.
Chem. Front. 2015, 2, 720−724.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.organomet.0c00250
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We are grateful to the National Science Foundation (Grant
CHE-1565923 to O.V.O.) for the support of this research.
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