Catalyzed hydroboration of nitrostyrenes and 4-vinylaniline: A mild and selective route to aniline derivatives containing boronate esters

Article abstract of DOI:10.1016/j.tetlet.2006.01.144

Transition metal catalyzed reactions of catecholborane (HBcat; cat = 1,2-O₂C₆H₄) with β-nitrostyrene and 3-nitrostyrene lead to products derived from competing hydrogenation and hydroboration of the alkene unit along with reduction of the nitro group. Hydroboration of 4-vinylaniline gave regioselective formation of either the branched or the linear organoboronate ester depending upon the catalyst precursors (i.e., RhCl(PPh₃)₃ or Rh(acac)(dppe) vs [Cp*IrCl₂]₂) used to facilitate this reaction. Hydroboration products were converted to air-stable primary amines by addition of pinacol.

Full text of DOI:10.1016/j.tetlet.2006.01.144

Tetrahedron Letters 47 (2006) 2419–2422
Catalyzed hydroboration of nitrostyrenes and
4-vinylaniline: a mild and selective route to aniline derivatives
containing boronate esters
Christopher M. Vogels,a Andreas Deckenb and Stephen A. Westcotta,*
aDepartment of Chemistry, Mount Allison University, Sackville, NB, Canada E4L 1G8
bDepartment of Chemistry, University of New Brunswick, Fredericton, NB, Canada E3B 5A3
Received 18 November 2005; revised 27 January 2006; accepted 30 January 2006
Available online 20 February 2006
Abstract—Transition metal catalyzed reactions of catecholborane (HBcat; cat = 1,2-O2C6H4) with b-nitrostyrene and 3-nitrostyrene
lead to products derived from competing hydrogenation and hydroboration of the alkene unit along with reduction of the nitro
group. Hydroboration of 4-vinylaniline gave regioselective formation of either the branched or the linear organoboronate ester
depending upon the catalyst precursors (i.e., RhCl(PPh3)3 or Rh(acac)(dppe) vs [Cp*IrCl2]2) used to facilitate this reaction. Hydro-
boration products were converted to air-stable primary amines by addition of pinacol.
Ó 2006 Elsevier Ltd. All rights reserved.
The hydroboration of alkenes and alkynes, which con-
stitutes the addition of a B–H bond across a carbon–car-
bon multiple bond, is a remarkably important reaction
in organic synthesis.1 Although simple boron hydride
reagents such as borane (H3BÆX, where X is a Lewis-
base) and 9-borabicyclo[3.3.1]nonane react readily with
alkenes at room temperature, hydroborations with
catecholborane (HBcat, cat = 1,2-O2C6H4) generally
require elevated temperatures. The discovery that transi-
tion metals can be used to catalyze the addition of
HBcat to organic substrates has become an important
and well-established technique.2 These reactions can
have regio-, chemo-, or stereoselectivities, complemen-
tary, or more remarkably, opposite to those from prod-
ucts obtained via the uncatalyzed variant. For example,
hydroborations of vinylarenes (ArCH@CH2) with
HBcat proceed to give selectively either the expected
linear product (ArCH2CH2Bcat) or the branched prod-
uct (ArCH(Bcat)CH3), depending upon the choice of
catalyst used to affect this transformation.3
gous reactions with heteroatom-containing substrates.3,4
In an effort to expand the scope of metal catalyzed
hydroborations, and generate novel aminoboron
compounds, we have examined reactions of related
nitrostyrene and vinylaniline derivatives with HBcat
and report our results herein. We have found that addi-
tion of excess HBcat (up to 8 equiv) to b-nitrostyrene
(trans-C6H5CH@CHNO2) using a rhodium catalyst
(typically RhCl(PPh3)3 or Rh(acac)(dppe); where
acac = acetylacetonato and dppe = 1,2-bis(diphenyl-
phosphino)ethane) gave only PhCH2CH2NO2 and
B2cat3.5 The formation of these products arises presu-
mably as a result of nucleophilic degradation of the
starting dialkoxyborane into B2cat3 and dihydrogen.
The liberated dihydrogen would add to the rhodium to
form an active hydrogenation catalyst, which could
react subsequently with the starting alkene to give
PhCH2CH2NO2.6
We then examined the rhodium catalyzed hydrobora-
tion of 3-nitrostyrene (3-O2NC6H4CH@CH2) to see if
altering the position of the nitro group had any effect
on the reaction pathway. Unfortunately, the catalyzed
addition of 1 equiv of HBcat gave only hydrogenation
product, 3-O2NC6H4CH2CH3 and unreacted starting
material, arising from degradation of the borane (Table
1, entry 1). However, in the case of 3-nitrostyrene,
addition of excess HBcat (8 equiv) using the rhodium
catalysts described above gave selective formation of
Although a considerable amount of research has focused
on the catalyzed hydroboration of simple unsaturated
hydrocarbon systems, much less is known about analo-
Keywords: Aminoboron; Catalysis; Hydroboration; Regioselectivity.
*
Corresponding author. Tel.: +1 506 364 2372; fax: +1 506 364
2313; e-mail: swestcott@mta.ca
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.01.144

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C. M. Vogels et al. / Tetrahedron Letters 47 (2006) 2419–2422
Table 1. Hydroboration of 3-nitrostyrene
+
N(Bcat)2
N(Bcat)2
[5 mol% cat.]
Bcat
+
HBcat
1b
1a
C6D6
NO2
catB
+
NO2
NO2
1c
1d
Entry
Catalyst
HBcat
1aa
1ba
1ca
1da
1
2
3
4
RhCl(PPh3)3
RhCl(PPh3)3
Rh(acac)(dppe)
[Cp*IrCl2]2
1.1
8
8
0
2
2
0
2
98
98
0
0
0
0
98
0
0
1.1
98 (72)
2
Values in parentheses are of isolated yields.
a Determined by multinuclear NMR spectroscopy and confirmed by GC/MS.
the branched hydroboration product 3-(catB)2NC6H4-
CH(Bcat)CH3 (1b) (>98% by H NMR spectroscopy,
rhodium catalyzed reactions. For instance, the linear
hydroboration product 3-O2NC6H4CH2CH2Bcat (1c)
could be generated as the major product in reactions
using only 1 equiv of HBcat (Table 1, entry 4). Remark-
ably, degradation of HBcat, and hence competing
reduction of the nitro group is not observed to any sig-
nificant extent in reactions using this catalyst system.
This observation suggests that catalysis with this precur-
sor may not necessarily proceed via conventional path-
ways that invoke initial oxidative addition of HBcat to
the metal center.14 The iridium catalyzed hydroboration
of alkenes using pinacolborane (HBpin; pin = 1,2-
O2C2Me4) is also known to give the corresponding pri-
mary boronate ester products.14c,d Attempts to catalyze
this reaction with HBpin, using either the rhodium or
iridium complexes, led to extensive degradation of the
borane along with the formation of significant amounts
of hydrogenation products (1a and 1d).
1
entries 2 and 3) along with minor amounts of unwanted
hydrogenation product 3-(catB)2NC6H4CH2CH3 (1a).
Reactions could be carried out in a variety of solvents
(benzene, toluene, THF, etc.) without significant loss
of selectivity. Remarkably, concurrent reduction of the
nitro group is observed in these reactions along with
considerable degradation of HBcat into B2cat35 and cat-
BOBcat.7 It is plausible that the dihydrogen that is also
formed by this degradation reaction is responsible, in
conjunction with the metal catalyst, for reducing the
nitro group to the corresponding amine derivative.
Excess HBcat would then react rapidly with the acidic
NH bonds to give products containing N(Bcat) bonds,
and once again liberating H2. To confirm that the nitro
group was being reduced in these reactions, we indepen-
dently converted 4-nitroanisole into 4-anisidine, and
subsequently 4-(catB)2NC6H4OMe, under identical con-
ditions (Scheme 1). In a similar study, organomagne-
sium reagents were used to reduce nitrosoarenes to
polyfunctional diarylamines.8
The molecular structure of 1c15 is shown in Figure 1
and the B–O bond distances of 1.390 (1) and 1.392
˚
(1) A are typical for those observed in other Bcat
structures where the boron is three coordinate.16 No
appreciable intermolecular interaction between the
Lewis acidic boron atom and the nitro group is observed
in the solid state. Addition of pinacol to compound 1c
gave 3-O2NC6H4CH2CH2Bpin (1f), whereby subsequent
hydrogenation using Pd/C gave the corresponding air-
stable aniline derivative 3-H2NC6H4CH2CH2Bpin (1g)
in moderate yield (46%).
In this study, the air-stable aniline derivative 3-H2N-
C6H4CH(Bpin)CH3 (1e, pin = 1,2-O2C2Me4)9 was
prepared and isolated in low yield (26%) by addition of
pinacol.10 The synthesis of amines containing boronate
esters is of considerable interest owing to their use in
Suzuki–Miyaura cross-coupling reactions1b and their
potent biological activities.11 The difficulty in preparing
primary amines containing boronate esters, however,
has previously limited their potential applications.12
The results from reactions with nitrostyrene prompted
us to investigate the catalyzed hydroboration of com-
mercially available 4-vinylaniline. While reactions of
allylamine gave complex product distributions arising
from competing degradation and isomerization reac-
Interestingly, using the iridium catalyst precursor
[Cp*IrCl2]213, the regioselectivities for the hydrobora-
tion reaction could be inverted in comparison to the
6 HBcat
MeO
NO
MeO
N(Bcat)
2
+ 2catBOBcat + 3H
2
2
5 mol% Rh
24 h
Scheme 1. Rhodium catalyzed reduction of 4-nitroanisole with HBcat.

C. M. Vogels et al. / Tetrahedron Letters 47 (2006) 2419–2422
2421
air-stable aniline derivatives containing boronate
esters that are difficult to prepare by conventional tech-
niques. Future work in this area will be to examine
asymmetric variants as well as expand the scope of these
reactions.
Acknowledgments
Thanks are extended to the Natural Science and
Engineering Research Council of Canada, the Canada
Research Chairs/Canadian Foundation for Innova-
tion/Atlantic Innovation Foundation programs and
Mount Allison University for financial support. We also
thank Dan Durant and Roger Smith for expert technical
assistance, Dr. Peter Walther (BASF Corporation) and
an anonymous reviewer for helpful comments.
Figure 1. Molecular structure of 1c with ellipsoids drawn at the 30%
probability level. Hydrogen atoms have been omitted for clarity.
˚
Selected bond lengths (A) and angles (deg): C(1)–B(12) 1.547(1); N(9)–
O(10) 1.226(1); N(9)–O(11) 1.232(1); B(12)–O(13) 1.390(1); B(12)–
O(14) 1.392(1); O(13)–B(12)–O(14) 111.15(8); O(13)–B(12)–C(1)
122.83(8); O(14)–B(12)–C(1) 126.02(8).
tions,4b hydroboration of 4-vinylaniline using either
RhCl(PPh3)3 (Table 2, entry 2) or Rh(acac)(dppe) (entry
3) with excess HBcat gave formation of the branched
product 4-(catB)2NC6H4CH(Bcat)CH3 (2b) along with
minor amounts of hydrogenation product 4-(catB)2-
NC6H4CH2CH3 (2a), as evidenced by multinuclear
NMR spectroscopy. Reactions with only 1 equiv of
HBcat gave a mixture of hydrogenation products, 2a.
Addition of pinacol to 2b, however, once again gave
the novel air-stable compound 4-H2NC6H4CH(Bpin)-
CH3 (2d).
Supplementary data
Experimental details describing the synthesis, character-
ization, and analysis of the products are provided along
with complete X-ray data for compound 1c. Full details
of the crystal structure investigation can also be
obtained from the Director of the Cambridge Crystallo-
graphic Data Centre, 12 Union Road, Cambridge CB2
1EZ, UK. Supplementary data associated with this arti-
cle can be found, in the online version, at doi:10.1016/
j.tetlet.2006.01.144.
The linear isomer 4-(catB)2NC6H4CH2CH2Bcat (2c)
could be generated using the [Cp*IrCl2]2 catalyst system,
however, this reaction suffered from competing hydro-
genation to give significant amounts of 2a (entry 4).
The corresponding pinacol derivative 4-H2NC6H4-
CH2CH2Bpin (2e)17 was isolated in moderate yield.
Attempts to prepare 2e directly from the catalyzed addi-
tion of pinacolborane (HBpin) using RhCl(PPh3)3 gave
only 4-(pinB)NHC6H4CH2CH3, where the correspond-
ing hydroboration reaction again appears to be too slow
to compete with the hydrogenation pathway.
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