Alkene isomerization-hydroboration promoted by phosphine-ligated cobalt catalysts

Article abstract of DOI:10.1021/acs.orglett.5b01135

Generated in situ from air-stable cobalt precursors or readily synthesized using NaHBEt₃, (PPh₃)₃CoH(N₂) was found to be an effective catalyst for the hydroboration of alkenes. Unlike previous base-metal catalysts for alkene isomerization-hydroboration which favor the incorporation of boron at terminal positions, (PPh₃)₃CoH(N₂) promotes boron incorporation adjacent to π-systems even in substrates where the alkene is at a remote position, enabling a unique route to 1,1-diboron compounds from α -dienes.

Full text of DOI:10.1021/acs.orglett.5b01135

Letter
pubs.acs.org/OrgLett
Alkene Isomerization−Hydroboration Promoted by Phosphine-
Ligated Cobalt Catalysts
Margaret L. Scheuermann, Elizabeth J. Johnson, and Paul J. Chirik*
Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States
S
* Supporting Information
ABSTRACT: Generated in situ from air-stable cobalt precursors or readily
synthesized using NaHBEt3, (PPh3)3CoH(N2) was found to be an effective catalyst
for the hydroboration of alkenes. Unlike previous base-metal catalysts for alkene
isomerization−hydroboration which favor the incorporation of boron at terminal
positions, (PPh3)3CoH(N2) promotes boron incorporation adjacent to π-systems even
in substrates where the alkene is at a remote position, enabling a unique route to 1,1-
diboron compounds from α,ω-dienes.
Scheme 1. Iron- and Cobalt-Catalyzed Alkene Isomerization−
Hydroboration
oron-containing molecules are valuable synthons for a range
1
Bof organic transformations. Organoboron compounds are
the nucleophilic component of Suzuki−Miyaura cross couplings,
one of the most widely employed methods for carbon−carbon
bond formation in the pharmaceutical industry.2 While aryl
boronates are the most commonly used substrates,3 recent
advances in cross-coupling catalysis have extended the method to
alkyl and benzylic organoboronates often operating with high
enantiospecificity.4
The advent and maturation of these methods motivates
efficient, selective, and sustainable synthetic routes to alkyl
boronate esters. The metal-catalyzed hydroboration of alkenes is
an attractive approach for the synthesis of secondary alkyl
boronate esters given its vast precedent and atom economy.1
Organometallic and coordination complexes of rhodium,
iridium, and group 4 metallocenes have dominated the catalyst
landscape but suffer from potential economic and environmental
drawbacks and, in many cases, have limited substrate scope or
offer poor selectivity.1 Renewed interest in base-metal catalysis
has resulted in the discovery of copper,5 iron, and cobalt catalysts
for alkene hydroboration.6−10 The iron and cobalt catalysts offer
the distinguishing feature of promoting alkene isomerization−
hydroboration with high terminal selectivity. In many cases, no
matter the starting position of the CC bond, carbon−boron
bond formation is highly selective for the terminal position of the
alkyl chain (Scheme 1).
The majority of these catalysts are supported by redox-active
or strongly π-acidic ligands,10 raising the question if whether
more classical innocent-type ligands are also effective. Under-
standing such influences will open the scope of metal−ligand
combinations available for base-metal-catalyzed hydroboration
and ultimately may enable the discovery of new catalysts. Here,
we describe the catalytic performance of cobalt−phosphine
complexes in alkene hydroboration and highlight features
distinct from those with redox-active supporting ligands.
Our studies commenced with the evaluation of combinations
of commercially available and ideally air-stable cobalt precursors
and phosphine ligands to promote catalytic carbon−boron bond
formation. Inspired by our recent observation of cobalt-catalyzed
reduction of formate using silanes,11 cobalt(II) bis(carboxylates)
were selected as the base-metal precursors. Reagents of this type
are air-stable and among the most inexpensive sources of cobalt.
Phosphines were chosen as supporting ligands because of their
commercial availability, their electronic and steric modularity,
and the recent observation that cobalt complexes supported by
strong field ligands promote catalytic C−H borylation.12,13
Benzofuran was selected as the initial substrate for evaluation as
both alkene hydroboration and C−H borylation reactions are
possible.
A THF solution of benzofuran and 1.6 equiv of HBPin (Pin =
pinacolate) was stirred under an N2 atmosphere with 5 mol % of
cobalt(II) acetate and 15 mol % of PPh3 for 72 h at 23 °C.
Received: April 17, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b01135
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Letter
Analysis of the isolated product by multinuclear NMR
spectroscopy established formation of 2,3-dihydrobenzofuran-
3-ylpinacolborane, arising from selective hydroboration of the
alkene with carbon−boron bond formation at the benzylic
position (Scheme 2, top). To our knowledge, the selective
Scheme 3. Synthesis of (PPh3)3CoH(N2)
Scheme 2. Selective Catalytic Hydroboration or Borylation of
Benzofuran with HBPin Promoted by Co(OAc)2/Phosphine
Mixtures
the in situ method was observed as complete conversion, and an
84% isolated yield was obtained after 2 h at 23 °C.
Table 1. Catalytic Alkene Hydroboration Promoted by
(Ph3P)3CoH(N2)
hydroboration of this substrate has not been reported.
Performing the analogous reaction with (MesPDI)CoCH3, an
active alkene hydroboration catalyst12 yielded trace amounts of
C−H borylation products rather than alkene hydrometalation.
The identity of the added phosphine had a dramatic effect on
the reaction outcome. Replacing PPh3 with PEt3 resulted in
quantitative and selective C−H borylation, demonstrating that
more electron-rich phosphines promote carbon−hydrogen
functionalization rather than hydrofunctionalization of the
alkene. The results highlight the versatility of the procedure as
the chemoselectivity of the reaction can be completely altered by
choice of added ligand.
The observation of a unique cobalt-catalyzed hydroboration of
benzofuran prompted investigation into the nature of the active
base-metal catalyst responsible for carbon−boron bond
formation. Monitoring the hydroboration of benzofuran with
Co(OAc)2 and PPh3 by 31P NMR spectroscopy indicated that
the bulk of the phosphine present (>90%) was free PPh3. An
unidentified paramagnetic cobalt compound, likely containing
1
only [OBPin] and carboxylate ligands, exhibited H NMR
a
Reaction conditions: 0.028 mmol of [Co], 1 mL of THF, 0.55 mmol
resonances at 15.16 and −25.64 ppm. A relatively minor peak at
of substrate, 0.55 mmol of cyclooctane internal standard, and 0.69
1
−21.20 ppm in the H NMR spectrum and corresponding 31P
b
mmol of HBPin. Reactions were monitored by GC, and the time
c
NMR resonance at 48.0 ppm were assigned to (PPh3)3CoH(N2),
a compound originally reported by Sacco and Rossi.14−17 It is
likely that (PPh3)3CoH(N2) arises from activation and reduction
of the cobalt acetate groups by HBPin driven by formation of
strong B−O bonds. A similar strategy has been employed for the
activation of palladium acetate precatalysts for cross-coupling
reactions18 and more recently with Ni(OAc)2 for generating C−
H borylation catalysts.19
Previous studies with (PPh3)3CoH(N2) have demonstrated
catalytic hydrosilylation of 1-hexene with SiH(OEt)3,20 and
related alkene hydroboration reactions therefore seemed
plausible. To test this hypothesis, a new, reliable synthetic
route to (PPh3)3CoH(N2) was devised whereby (PPh3)2CoCl2
was treated with 2 equiv of NaHBEt3 in the presence of PPh3
(Scheme 3). This new method is highly reproducible and
eliminates the need for difficult to handle and ill-defined
aluminum reductants used in the original route.14,21 During the
course of these investigations, higher resolution X-ray crystallo-
graphic data were collected on the compound and are reported in
the Supporting Information.
noted is the time to >98% conversion. Ratios represent the relative
1
amounts of isomeric hydroboration products as determined by H
NMR integration.
The scope of (PPh3)3CoH(N2) promoted alkene hydro-
boration was evaluated. Each catalytic reaction was conducted
with a 0.55 M THF solution of the alkene and 1.25 equiv of
HBPin at 23 °C. The results of these studies are reported in Table
1. As with benzofuran, the hydroboration of indene is selective
for the benzylic position (entry 2). Styrene (entry 3) and cis-β-
methylstyrene also underwent selective hydroboration with high
activity, as complete conversion was observed in 1.0 h and 0.5 h,
respectively. Stilbene and 4-methoxystilbene (entry 4) were also
effective substrates with the latter exhibiting a slight preference,
1.6:1 for carbon−boron bond formation at the benzylic position
adjacent to the more electron-deficient arene. With 1-
octenylpinacolborane (entry 5), selective formation of the 1,1-
diboron product was observed. Dihydropyran (entry 6)
underwent hydroboration with regiochemistry opposite of
what is observed using BH3.22 In all cases, good to high isolated
yields were obtained, and separation of the product from the
catalyst residue was readily accomplished by passage through
silica.
The catalytic alkene hydroboration activity of (PPh3)3CoH-
(N2) was then evaluated using HBPin and benzofuran as
substrates (Table 1, entry 1). Dramatically improved activity over
B
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To explore the generality of this method further, the cobalt-
catalyzed hydroboration of allylbenzene with HBPin was
explored. With 5 mol % of (Ph3P)3CoH(N2), complete
conversion to a 83:17 mixture of products was observed with
the major product identified as 1-phenylpropylpinacolborane (A,
Scheme 4). The minor product, 3-phenylpropylpinacolborane
(C), arises from C−B bond formation at the alkyl terminus.
Because (PPh3)3CoH(N2) is a known alkene isomerization
catalyst,18,21 a protocol was devised to synthesize benzylic
organoboronate esters selectively via tandem isomerization−
hydroboration. The general procedure involved premixing the
alkene and cobalt precursor for 1 h in THF prior to the addition
of HBPin. As reported in Table 2, this method is effective for a
Table 2. Catalytic Alkene Isomerization−Hydroboration with
HBpin and 5 mol % of (Ph3P)3CoH(N2)
Scheme 4. Hydroboration of Allylbenzene with HBPin Using
Various Cobalt Precursors
a
Reaction conditions: 0.028 mmol of [Co], 1 mL of THF, 0.55 mmol
a
of allylbenzene, 0.55 mmol of cyclooctane, and 0.69 mmol of HBPin.
[Co] was added last. After the reactions attained >98% conversion,
relative ratio of A:B:C determined from GC integration and
Reaction conditions: 0.028 mmol of (PPh3)3CoH(N2), 1 mL of
b
THF, 0.55 mmol of benzofuran, 0.55 mmol of cyclooctane. HBPin
(0.69 mmol) was added after 1 h. Reactions were monitored by GC,
and the time noted is the time to >98% conversion. Ratios represent
b
c
normalized to 100. Response factors were not determined; however,
c
d
their ratio is constant. With 5 mol % of PPh3 added. With 1.5 equiv
of HBPin.
the relative amounts of isomerization−hydroboration product shown
and the isomer with boron incorporated at the terminal position of the
alkyl chain. The ratios were determined by 1H NMR integration.
d
e
Stirred for 5 h prior to HBPin addition. Hexylpinacolborane was also
f
identified in the isolated product. No other isomers were isolated.
While cobalt-catalyzed alkene isomerization−hydroboration is
now well precedented, most catalysts favor products arising from
terminal carbon−boron bond formation. With precious metals,
only the rhodium-catalyzed reaction of allylbenzene with BH3·
THF favors branched products.23 The unusual preference for
benzylic carbon−boron bond formation in allylbenzene hydro-
boration with HBPin and by (Ph3P)3CoH(N2) prompted
comparison with other cobalt precatalysts to gauge how the
supporting ligand impacts the selectivity of the reaction,
information that will ultimately prove useful in future catalyst
design.
As presented in Scheme 4, the branched selectivity for the
hydroboration of allylbenzene in the presence of 5 mol % of
(PPh3)2CoN(SiMe3)2, a compound reported by Fout and co-
workers in the context of catalytic C−N cross coupling,24 was
indistinguishable from (PPh3)3CoH(N2), demonstrating the
ratio of phosphine to cobalt does not influence selectivity. In
contrast, cobalt compounds bearing sterically demanding, aryl-
substituted, and redox-active α-diimine and bis(imino)pyridine
chelates yielded 3-phenylpropylpinacolborane (C) as the major
product with high selectivity, highlighting the preference of these
catalysts for forming carbon−boron bonds at terminal positions.
With (terpy)CoCH2SiMe3 (terpy = terpyridine), a mixture of
products was obtained with a slight preference for benzylic C−B
bond formation over the terminal position.
family of alkenyl arenes with generally high selectivity for the
benzylic product. Complete conversion and good to high
isolated yields were obtained. Isomerization over a 12-carbon
chain (entry 3) highlights the scope of the method, although a
longer premixing time of 5 h was required for optimal selectivity.
Boronate esters (entry 4) also favored isomerization and
provided a route to valuable 1,1-diboron compounds from
readily available α,ω-dienes.25 The unique role of aryl and
boronate ester functional groups in promoting the isomerization
is highlighted by entry 5, where cobalt-catalyzed hydroboration
of the allylsilane produced exclusive terminal selectivity.
To explore the selectivity of cobalt-catalyzed hydroboration
following alkene isomerization, a deuterium labeling study was
conducted. Addition of DBPin to 4-phenyl-1-butene following 1
h of premixing with (PPh3)3CoH(N2) revealed incorporation of
the isotopic label exclusively at the position β to the arene ring
(Scheme 5). The selective incorporation of the deuterium at this
position indicates that C−B bond formation at the benzylic
position is faster than isomerization of 1-phenylbutene, formed
from 4-phenyl-1-butene during the premixing period, as
isomerization would result in deuterium scrambling.
The erosion of selectivity observed in experiments without
premixing of the alkene and catalyst demonstrate that for the
initially formed terminal cobalt−alkyl, the rates of C−B bond
C
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Organic Letters
Letter
W. Neil Palmer (Princeton University) for assistance with X-ray
crystallography and mass spectrometry, respectively.
Scheme 5. Catalytic Isomerization−Hydroboration of 4-
Phenyl-1-butene Using DBPin
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formation and β-hydride elimination are competitive. The slower
isomerization of 1-phenylbutene relative to 4-phenylbutene
likely derives from the preferential formation of η3-benzyl
intermediates following alkene insertion into the Co−H, or in
the case of boronate ester directed reactions, coordinatin of an
oxygen atom. Cobalt complexes with η3-benzyl ligands have been
observed previously,26 and similar intermediates have been
invoked to account for the selectivity for branched products in
the rhodium-catalyzed hydroboration of styrene.27 Formation of
an η3-benzyl cobalt benzyl intermediate is also consistent with
the observed catalyst effects reported in Scheme 4. More
sterically hindered ligands such as aryl-substituted α-diimine and
bis(imino)pyridines favor carbon−boron bond formation from
terminal alkyl intermediates even when the starting alkene is in
an internal position.
Additional experiments were conducted to gain insight into
the nature of the catalytic active cobalt compound and identity of
the resting state. Monitoring the catalytic hydroboration of
benzofuran with HBPin in THF-d8 with 10 mol % of
(PPh3)3CoH(N2) by 1H and 31P NMR spectroscopies revealed
no detectable change to the catalyst precursor over the
hydroboration reaction. To establish the potential role of
phosphine dissociation, the hydroboration of benzofuran was
conducted with a solution containing 0.028 M (PPh3)3CoH(N2)
in the presence of variable amounts of added PPh3. Upon
doubling the concentration of added phosphine from 0.11 to
0.22 M, the initial relative rate constants decreased by a factor of
2. The inhibition by added phosphine, in conjunction with
observation of (PPh3)3CoH(N2) as the resting state, support
PPh3 dissociation as an entry point into the catalytic cycle.
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effective for alkene hydroboration with nonterminal selectivity
offering a route to benzylic boronate esters from a variety of
alkenes or 1,1-diboron compounds from α,ω-dienes.
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S
* Supporting Information
Complete experimental procedures, characterization data for all
new compounds, and crystallographic data in CIF format. The
Supporting Information is available free of charge on the ACS
Publications website at DOI: 10.1021/acs.orglett.5b01135.
AUTHOR INFORMATION
Corresponding Author
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*E-mail: pchirik@princeton.edu.
Notes
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The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Addy Fund from the Andlinger Center for Energy
and the Environment at Princeton University and Princeton
University for financial support. We also thank Iraklis Pappas and
D
DOI: 10.1021/acs.orglett.5b01135
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