Iron-Catalyzed e?Selective dehydrogenative borylation of vinylarenes with pinacolborane

Article abstract of DOI:10.1021/acscatal.6b02654

We report the dehydrogenative borylation of vinylarenes with pinacolborane (HBpin) catalyzed by an iron(0) complex “(PMe₃)₄Fe”. A variety of monosubstituted and disubstituted vinylarenes underwent this iron-catalyzed transformation, affording E-vinyl boronate esters (VBEs) selectively in hi h ields. In addition we coupled this iron-catal zed dehydrogenative borylation with further transformations of the resulting vinyl boronate esters and developed various one-pot procedures for the functionalization of the vinylic C?H bonds in vinylarenes. Mechanistic studies reveal that this Fe-catalyzed reaction proceeds through syn-insertion of vinylarenes into a Fe-boryl species followed by β-hydrogen elimination from a syn coplanar conformation of the borylalkyl iron intermediate.

Full text of DOI:10.1021/acscatal.6b02654

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Letter
Iron-Catalyzed E-Selective Dehydrogenative
Borylation of Vinylarenes with Pinacolborane
Chao Wang, Cai-Zhi Wu, and Shaozhong Ge
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.6b02654 • Publication Date (Web): 07 Oct 2016
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ACS Catalysis
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Iron-Catalyzed E-Selective Dehydrogenative Borylation of Vi-
nylarenes with Pinacolborane
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Chao Wang, Caizhi Wu, and Shaozhong Ge*
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore
KEYWORDS: iron, borylation, dehydrogenative, vinylarenes, homogenous catalysis
ABSTRACT: We report the dehydrogenative borylation of vinylarenes with pinacolborane (HBpin) catalyzed by an iron(0) com-
plex “(PMe3)4Fe”. A variety of mono- and di-substituted vinylarenes underwent this iron-catalyzed transformation, affording E-
vinyl boronate esters (VBEs) selectively in high yields. In addition, we coupled this iron-catalyzed dehydrogenative borylation with
further transformations of the resulting vinyl boronate esters and developed various one-pot procedures for the functionalization of
the vinylic C-H bonds in vinylarenes. Mechanistic studies reveal that this Fe-catalyzed reaction proceeds through syn-insertion of
vinylarenes into a Fe-boryl species followed by
intermediate.
β-hydrogen elimination from a syn coplanar conformation of the borylalkyl iron
Vinyl boronate esters (VBEs) are useful building blocks in
organic synthesis. They have been employed as synthetic pre-
cursors to alkenyl halides and aldehydes and undergo a range
of metal-catalyzed cross-coupling reactions.1 More interesting-
complexes (dmpe)FeR2 (R = Me or H), adds to pinacolborane
(HBpin) to form a hydrido iron boryl species.15 We envision
that vinylarenes can undergo 2,1-migratory insertion into the
Fe-B or Fe-H bond (scheme 1) to give the iron species I or II,
respectively. The subsequent C-H or C-B reductive elimina-
tion from intermediates I or II can take place to afford alkyl
boronate esters (hydroboration selectivity). Indeed, iron com-
plexes have recently been emerging as highly active catalysts
for hydroboration of alkenes with HBpin.16 Alternatively, spe-
ly,
β-aryl VBEs are important intermediates to prepare stil-
benoid compounds, which are ubiquitous in biologically active
molecules2 and material sciences.3 In general, VBEs can be
prepared by hydroboration of alkynes,4 lithiation of alkenyl
halides followed by reactions with trialkoxyborates,5 metal-
catalyzed borylation of alkenyl halides or pseudohalides,6
cross-metathesis of alkenes with pinacolvinylboronates,7 or a
boryl-Heck reaction of alkenes with chloroborane.8 However,
these methods require the pre-activation of the vinyl group or
cies I can undergo β-hydrogen elimination to produce vinyl
boronate esters (dehydrogenative borylation selectivity). This
dehydrogenative process was identified as a minor pathway
and gave vinyl boronate esters as byproducts for the iron-
catalyzed alkene hydroboration.16d In view of broad synthetic
applications of vinyl boronate esters (VBEs), we are interested
in developing an effective and selective iron-catalyzed dehy-
drogenative borylation of alkenes to prepare VBEs.
are not suitable to prepare β,β-di-substituted VBEs.
Catalytic dehydrogenative borylation of alkenes is an attrac-
tive alternative to prepare vinyl boronate esters. However, this
dehydrogenative borylation reaction is not well studied as it
has been viewed as a “deleterious” side reaction for metal-
catalyzed hydroboration of alkenes.9 There are a few reports
on this catalytic dehydrogenative borylation process, but the
catalysts for this reaction are limited to noble metals, such as
Rh,10 Pd,11 Ir,12 and Pt13. In addition, the scope of alkenes that
undergo this catalytic reaction is mainly tested with mono-
substituted alkenes and cyclic alkenes.10-12 The dehydrogena-
tive borylation of 1,1-disubstituted alkenes (with three exam-
ples) has been achieved with a palladium catalyst by reactions
with a diboron(4) compound B2pin2.11b The dehydrogenative
borylation of 1,1-disubstituted alkenes suffers from either low
reactivity or low selectivity.10c, f Effective and selective dehy-
drogenative borylation of disubstituted terminal alkenes is
Scheme 1. Expected pathways for Iron-Catalyzed Reac-
tions of Alkenes with Pinacolborane
R
LFeH2
H
R
Bpin
H
L Fe
R
Ar
Bpin
LFe
Bpin
Ar
2,1-insertion
b-H elimination
Ar
dehydrogenative
borylation
(I)
C-H reductive
elimination
R
Bpin
R
Ar
Ar
R
C-B reductive
elimination
Bpin
H
Ar
R
CH3
Bpin
LFe
LFe
CH3
hydroboration
Bpin
Ar
2,1-insertion
(II)
particularly important because products from this process, β,β-
To develop an iron-catalyzed dehydrogenative borylation
reaction, we need to identify an iron catalyst that favors
di-substituted vinyl boronate esters, are not accessible from
β
-
catalytic hydroboration of alkynes.14
hydrogen elimination. As an increase in electron-donating
ability and a decrease in steric hindrance of ancillary ligands
Recently, phosphine/iron complexes have been reported to
catalyze the C-H borylation of arenes.15 The low-valent iron(0)
species, generated in situ by irradiation of well-defined iron
increase the rate of
complexes with a small and electron-rich trimethylphosphine
β
-hydrogen elimination,17 we targeted iron
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(PMe3) as catalysts for the dehydrogenative borylation reac- The scope of vinylarenes that undergo this transformation is
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tion. We chose an iron complex (PMe3)4Fe as a single-
component catalyst precursor, as this iron compound can be
readily accessible through the reduction of FeCl2 with magne-
sium in the presence of PMe3 in THF.18
summarized in Table 2. In general, a wide range of di- and
mono-substituted vinylarenes containing electronically varied
aryl groups reacted smoothly at 50 °C, yielding the corre-
sponding E-vinyl boronate esters (1a−1v and 2a−2m) in mod-
est to excellent isolated yields (51−94%). The GC-MS analy-
sis on the crude mixtures of these reactions indicated the for-
mation of trace amounts (< 2%) of Z-vinyl boronate esters.
The low isolated yields for compounds 1o, 1p, and 1s resulted
from low conversions of the corresponding vinylarenes.
We initiated this study by evaluating the conditions for the
(PMe3)4Fe-catalyzed reaction of α-methylstyrene with HBpin.
The selected examples of these experiments are summarized in
Table 1. These reactions were conducted with HBpin as the
limiting reagent and a variety of alkenes as the hydrogen ac-
ceptor in the presence of 5 mol % of (PMe3)4Fe at 50 °C. The
reaction conducted in the absence of hydrogen acceptors af-
forded only a trace amount of desired product (entry 1), and
this result indicated that α-methylstyrene is not an effective
hydrogen acceptor for this reaction. Similar results were ob-
tained for the reaction with norbornadiene as a hydrogen ac-
ceptor (entry 2). Improved results were obtained for the reac-
tions with other monoalkenes as hydrogen acceptors (entries
3−6) and the reaction conducted in the presence of norbornene
selectively provided the product derived from the dehydro-
genative borylation in high yield (entry 3). The stereochemis-
try for the VBE product was confirmed to be trans by the 2D
NMR (NOESY) analysis. We also tested the reaction with α-
methylstyrene as the limiting reagent in the presence of nor-
bornene (entry 7). This reaction gave the desired product in
78% GC yield together with a significant amount (20%) of
alkyl boronate ester derived from hydroboration of nor-
bornene.
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Table 2. The Scope of Vinylarenesa
(PMe3)4Fe (3-5 mol %)
norbornene (2 equiv.)
R
R
+
H
Bpin
Bpin
Ar
Ar
hexane, 50 °C, 18 h
Me
Me
Me
Me
Me
Bpin
Bpin
O
Bpin
R
Bpin
R
O
R = F,
R = OMe, 1h, 89%
Me
1g, 89%
Me
1i, 79%
R = H,
1a, 93%
1j, 83%
R = CF3,
R = Me,
R = tBu,
1b, 75%
1c, 94%
1d, 86%
Me
Bpin
Bpin
R = OCF3, 1e, 86%
R = SO2Me, 1f, 80%
TBSO
1k, 62%
Me
O
1l, 71%
Me
Me
O
Me
Bpin
Bpin
H
Bpin
O
O
N
Ar
Ar: 2,6-iPr2-C6H3
Me
1n, 82%
1m, 90%
Me
1o, 63%
Me
Bpin
Me
Me
Table 1. Evaluation of the Reaction Conditionsa
Bpin
Bpin
O
Bpin
(PMe3)4Fe (5 mol %)
Me
1p, 62%
Me
1q, 83%
Me Me
1r, 82%
1s, 65%
O
O
Me
Me
additive (2 equiv)
+
H
B
Ph
Bpin
+
solvent, 50 °C, 18 h
Ph
Ph
Me
Ph
Bpin
1a'
1a
(1.2 equiv) (1.0 equiv)
Bpin
Bpin
Bpin
Bpin
yield (E/Z)(1a)b
yield (1a')b
entry
1
additive
----
solvent
hexane
MeO
<5% (99:1)
0
1t, 88%
1u, 84%
1v, 74%
1w, 74% (E/Z = 1:2)
Bpin
Bpin
Bpin
2
3
4
hexane
hexane
<5% (99:1)
95% (98:2)
58% (99:1)
0
0
0
Bpin
R
R2
R1
Ph2P
2a, 90%
2b, 88%
2c, 80%
2d, 80%
R = H,
R = Me,
R = tBu,
R = F,
R = OMe, 2e, 91%
R = NMe2, 2f, 90%
R1 = F, R2 = H, 2i, 91%
R1 = R2 = Me, 2j, 82%
Cl
(nbe)
2l, 60%
2k, 51%b
hexane
Bpin
Bpin
O
O
tBu
nBu
nbe
nbe
nbe
nbe
5
6
hexane
hexane
40% (99:1)
73% (98:2)
0
0
(MeO)3Si
R = Ph,
2g, 75%
2m, 81%
2n, 92%
R = Bpin, 2h, 74%
7c
8
hexane
toluene
78% (98:2)
58% (99:1)
33% (99:1)
35% (99:1)
0
0
0
0
aConditions: α-substituted vinylarene (0.600 mmol), HBpin
(0.500 mmol), (PMe3)4Fe (25.0 ꢀmol for 1a−1v; 15ꢀmol for
2a−2m), norbornene (1.00 mmol), hexane (1 mL), 50 °C, 18 h,
9
THF
10
1,4-dioxane
b
and isolated yields after column chromatography. 10 mol %
aConditions: α-methylstyrene (0.600 mmol), HBpin (0.500
mmol), iron precursor (25.0 ꢀmol), solvent (1 mL), 50 °C, 18 h.
bDetermined by GC analysis with dodecane as the internal stand-
ard. cα-methylstyrene (0.500 mmol), HBpin (0.600 mmol).
(PMe3)4Fe.
The dehydrogenative borylation of vinylarenes tolerates a
range of functionalities, including ether (1h, 1j, and 2e), al-
kene (1k), trifluoromethylether (1e), sulfone (1f), siloxy (1l
and 2m), imine (1o), tertiary amine (2f), tertiary phosphine
(2l), pinacolboryl (2h), and chloro (2k) moieties. Carbonyl,
cyano, and free hydroxyl and amino groups are not compatible
with the reaction conditions. However, vinylarenes containing
a ketone (1m and 2n) or aldehyde (1n) protected as acetal and
an alcohol (1l) protected as silyl ether reacted to afford the
corresponding VBE product in high yields. In addition, α-
methyl vinylfuran (1p) reacted to give the desired product in
modest yield (62%), but vinylpyridines did not undergo this
We tested various solvents for this dehydrogenative boryla-
tion and found that the solvent effect on this reaction was pro-
nounced (entries 3 and 8−10). This observed solvent effect
might result from the coordinating ability of these solvents
(1,4-dioxane ~ THF > toluene > hexane). In addition, we also
tested the combination of (PMe3)4Fe and chelating ligands for
this reaction and found that these reactions either did not pro-
ceed or afforded the desired products in lower yields (see the
SI for details).
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ACS Catalysis
transformation under the identified conditions. Furthermore, responding products with deuterium atoms located on both the
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dienes and trisubstituted alkenes do not undergo this Fe-
catalyzed dehydrogenative borylation under the identified
conditions.
α-methyl and the terminal vinylic carbons. The incorporation
of deuterium into norbornane was detected by the GC-MS
analysis (see the SI for the isotope analysis of norbornane).
These results support the formation of a Fe-H intermediate as
the H/D exchange occurs through the reversible olefin inser-
tion into the Fe-H/D bond. The reaction of 7-d2 with HBpin in
the absence of norbornene (C in Scheme 3) resulted in low
conversion (<10%) of vinylarene 7-d2. Analysis of the uncon-
We also tested vinylarenes containing an aliphatic or aro-
matic substituent at the α-position for this Fe-catalyzed pro-
cess. Increasing the steric bulkiness of these substituents from
Et (1q), n-Pr (1r), n-Hex (1s), i-Bu (1t), to CH2C(Me2)Ph (1u)
has little influence on this reaction and the corresponding E-
VBE products are isolated in similarly high yields. 1,1-
Diarylethenes (1v and 1w) also underwent this reaction to
afford the desired VBEs in good yields. However, the reaction
of 1,1-diarylethene (1w) containing two different aryl groups
gave a mixture of E- and Z-product, with the preference for Z-
isomer.
2
verted vinylarene by H NMR indicated the deuterium scram-
bling between the vinylic C-D and the α-methyl C-H.
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To reveal the origin of the E-selectivity for this Fe-catalyzed
transformation, we tested the reaction of E-7-d1 with HBpin to
check whether the vinylic C-H or C-D is substituted by the
Bpin group (D in Scheme 3). This reaction afforded the prod-
uct with deuterium on the α-methyl group (major) and the
terminal vinylic carbon (minor). Based on the results from
reactions C and D, we can not conclude whether the vinyl C-H
or C-D is substituted by the Bpin group.
Subsequently, we developed one-pot procedures for the
functionalization of vinylic C-H bonds in vinylarenes and the-
se results are listed in Scheme 2. This Fe-catalyzed dehydro-
genative borylation followed by halogenation with CuX2 (X =
Cl and Br, A in Scheme 2) or iodide (B in Scheme 2) provides
a one-pot method to synthesize E-vinyl halides (3a−3c) from
vinylarenes. Homologation of VBE generated in situ from the
vinylic C-H borylation of α-methylstyrene with LiCH2Cl af-
forded allylic boronate ester (4) in 66% yield (C in Scheme 2).
Oxidative hydrolysis of VBEs with NaBO3 (D in Scheme 2)
provided a sequential one-pot procedure to prepare α-aryl
aldehydes (5a−5b), which are not accessible by the Pd-
catalyzed direct α-arylation of aliphatic aldehydes.19 In addi-
tion, the VBEs generated in situ underwent the Pd-catalyzed
Suzuki coupling with aryl bromides to afford stilbenes (6a−6c)
in high yields (E in Scheme 2).
Scheme 3. Deuterium-Labeling Experiments
0.41 D
A)
(PMe3)4Fe (3 mol %)
nbe (2 equiv.)
Me
C(H/D)3
Bpin
H
D
+ DBpin
hexane, 50 °C, 6 h
H
(H/D)
52% yield
0.12 D
0.77 D
C(H/D)3
Bpin
B)
(PMe3)4Fe (3 mol %)
nbe (2 equiv.)
Me
+ HBpin
hexane, 50 °C, 6 h
D
(H/D)
49% yield
tBu
tBu
tBu
tBu
(7-d2)
0.42 D
0.38 D
Scheme 2. One-pot Procedures for the Functionalization of
Vinylic C-H bond
C)
Me
C(H/D)3
(PMe3)4Fe (3 mol %)
D
(H/D)
+ HBpin
Me
Me
hexane, 50 °C, 6 h
A: CuX2 (2 equiv)
THF/H2O, 70 °C
CH2BrCl (1.2 equiv)
BuLi (1.3 equiv)
0.80 D
D
(H/D)
X
tBu
Bpin
(7-d2)
0.79 D
0.65 D
THF, -78 °C
B: I2 (2 equiv.),
NaOH (aq., 3M)
THF, rt
C
4, 66%
Method A:
D)
X = Cl, 3a, 52%
X = Br, 3b, 80%
Method B:
Conditions in
R
(PMe3)4Fe (3 mol %)
nbe (2 equiv.)
Me
C(H/D)3
R
Table 1 or 2
Bpin
D
Bpin
+ HBpin
Ar
NaBO3•4H2O
(1.2 equiv)
NaOH (aq. 3M)
Ar
X = I, 3c, 78%
hexane, 50 °C, 6 h
H
(H/D)
Pd(OAc)2 (5 mol %)
P(tBu)3•HBF4 (10 mol %)
ArBr (0.8 equiv)
54% yield
tBu
R
R
(E-7-d1)
Me
0.18 D
H
<0.02D
E)
1,4-dioxane/H2O 1,4-dioxane, 100 °C
Me Me
Me Me
O
E
0 °C
0.79 D
(H/D)
0.71 D
(H/D)2
(H/D)
R = CF3, 6a, 80%
R = H, 6b, 84%
R = OMe, 6c, 96%
Ph
Ph
(PMe3)4Fe (5 mol %)
D
X = Me, 5a, 71%
X = Et, 5b, 76%
+ HBpin
hexane, 50 °C, 18 h
H
(H/D)
(8)
To study the activation of HBpin with a low-valent Fe(0)
complex, we conducted a stoichiometric reaction of (PMe3)4Fe
and HBpin. Well-resolved NMR spectra were not obtained for
this reaction. However, HR-MS (ESI) analysis of the reaction
mixture indicated the formation of (PMe3)4Fe(H)(Bpin), as
both cationic fragments [(PMe3)4Fe(H)]+ (m/z calc’d:
361.1195; found: 361.1192) and [(PMe3)4Fe(Bpin)]+ (m/z
calc’d: 487.2047; found: 487.2050) were observed. Such oxi-
dative addition between H-B and Fe(0) species was previously
reported for the reaction of HBpin with “(dmpe)2Fe(0)”.10
0.07 D
F)
Me Me
Ph
Me Me
Ph
0.79 D
+ HBpin
(PMe3)4Fe (5 mol %)
nbe (2 equiv.)
(H/D)
Bpin
hexane, 50 °C, 18 h
81% yield
H
(H/D)
(8)
(9)
0.71 D
We anticipated that a bulky alkyl group on the
α-position
could minimize the above-mentioned deuterium scrambling
observed for reaction C. To test this, trans-2,4-diphenyl-4-
methyl-1-[1D]-pentene (8) was subjected to this deuterium
scrambling reaction (E in Scheme 3) for this reaction. As ex-
pected, only trace amounts of deuterium are detected on the
allylic methylene group and the terminal Z-vinylic C-H posi-
tion. Subsequently, we tested this vinylarene for the Fe-
To understand the mechanism of this Fe-catalyzed dehydro-
genative borylation reaction, we conducted a series of deuteri-
um labelling experiments (Scheme 3). The reaction of α-
methylstyrene with DBpin (A in Scheme 3) and the reaction of
vinylarene 7-d2 with HBpin (B in Scheme 3) afforded the cor-
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The Supporting Information is available free of charge on the
ACS Publications website.
Experiment procedures and characterization data for reaction
products (PDF)
catalyzed dehydrogenative borylation reaction (F in Scheme
3). This reaction gave the trans-VBE (9) containing deuterium
at the vinylic position as the major product. These results indi-
cated that the vinylic C-H in vinylarene 8 was substituted by
the Bpin group.
1
2
3
4
AUTHOR INFORMATION
5
Lastly, the Z-isomer of 1a was subjected to the standard re-
6
7
8
9
action conditions for the dehydrogenative borylation of p,α-
Corresponding Author
dimethylstyrene, and <10% of Z-1a was isomerized to E-1a in
18 h (see the SI for details). This Z/E-isomerization further
supports the formation of the Fe-H intermediate. The low con-
version of Z-1a to E-1a was due to the slow migratory inser-
tion of tri-substituted alkene 1a into the Fe-H bond. Based on
this result, it is unlikely that the E-selectivity for this Fe-
catalyzed dehydrogenative borylation is originated from the
isomerization of Z-isomer.
* chmgsh@nus.edu.sg
Note
The authors declare no competing financial interest.
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ACKNOWLEDGMENT
This work was supported by the National University of Singapore
(R-143-000-614-133) and the fund from NUS Young Investigator
Award (R-143-000-630-133). The authors thank Dr. Rowan D.
Young and Dr. Simon Sung for conducting the HR-MS (ESI)
analysis.
Based on the results of the stoichiometric reaction and the
series of deuterium labelling experiments, we propose a cata-
lytic cycle depicted in Scheme 4 for this Fe-catalyzed boryla-
tion reaction. The key step for this reaction is the syn-insertion
REFERENCES
of vinylarene into the Fe-B bond followed by
elimination from a syn coplanar conformation of the iron
borylalkyl intermediate. The preference for -hydrogen elimi-
β-hydrogen
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β
nation from the borylmethylene group can be explained by the
formation of a more stable boryl-stabilized internal alkene,
due to the interaction of the empty p-orbital on boron with the
adjacent π-electrons of alkene. Minimizing the steric repulsion
between the aryl and Bpin groups by rotation of the Bpin
group away from the bulkier aryl group to place Hb syn to Fe
accounts for the observed E-selectivity.20
Scheme 4. The Proposed Catalytic Cycle for This Iron-
Catalyzed Dehydeogenative Borylation
HBpin
nba
Me
L4Fe(0)
(16e)
nbe
H
Me Me
Ar
Bpin
Ar
H
L = PMe3
(insertion)
L
4Fe
LFe
L4Fe
(18e)
Hb
Bpin
(18e)
β
R
-H elimination
R
Bpin
Ha
Ar
Ha
Hb
Ar
PMe3
PMe3
H
H
Hb
Bpin
Ha
L3Fe Bpin
L3Fe
R
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H. J. Am. Chem. Soc. 2014, 136, 2149-2161.
R
Ha
Ar
Ar
Hb
(16e)
(18e)
H
Bpin
L3Fe
R
Ha
(8) Reid, W. B.; Spillane, J. J.; Krause, S. B.; Watson, D. A. J. Am.
Chem. Soc. 2016, 138, 5539-5542.
Ar
(16e)
Hb
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In summary, we have developed a convenient and efficient
protocol for the synthesis of -aryl VBEs through dehydro-
β
genative borylation of vinylarenes with HBpin catalyzed by
(PMe3)4Fe. A broad range of mono- and disubstituted vi-
nylarenes underwent this reaction to afford E-VBEs in high
isolated yields. This Fe-catalyzed dehydrogenative process
provides a versatile foundation to develop various one-pot
procedures for functionalization of vinylic C-H bonds of vi-
nylarenes. Studies on dehydrogenative borylation of aliphatic
alkenes and other dehydrogenative functionalization reactions
of alkenes catalyzed by base metals are ongoing.
ASSOCIATED CONTENT
Supporting Information
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1
2
3
4
5
6
synthesize
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(20) The iron-catalyzed dehydrogenative borylation reaction of α-
isopropylstyrene with HBpin proceeded very sluggishly to low
converion (~10%), but produced a E/Z-mixture of vinyl boronate
esters.
(PMe3)4Fe (3-5 mol %)
norbornene (2 equiv)
O
B
O
O
R
R
+
HB
O
hexane, 50 °C, 18 h
Ar
Ar
R = H, Alkyl, or Aryl
37 examples
average yield: 80%
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