Rhodium-catalyzed dehydrogenative borylation of cyclic alkenes

Article abstract of DOI:10.1039/b921387b

A rhodium-catalyzed dehydrogenative borylation of cyclic alkenes is described. This reaction provides direct access to cyclic 1-alkenylboronic acid pinacol esters, useful intermediates in organic synthesis. Suzuki-Miyaura cross-coupling applications are also presented. The Royal Society of Chemistry 2010.

Full text of DOI:10.1039/b921387b

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Rhodium-catalyzed dehydrogenative borylation of cyclic alkeneswz
Azusa Kondoh and Timothy F. Jamison*
Received (in Cambridge, UK) 14th October 2009, Accepted 10th December 2009
First published as an Advance Article on the web 5th January 2010
DOI: 10.1039/b921387b
A rhodium-catalyzed dehydrogenative borylation of cyclic
alkenes is described. This reaction provides direct access to
cyclic 1-alkenylboronic acid pinacol esters, useful intermediates
in organic synthesis. Suzuki–Miyaura cross-coupling applications
are also presented.
some advantages to these previously reported methods. In
contrast to the Szabo method, which uses a large excess of
´
alkene (as solvent), we have found that only a slight excess of
alkene is required in this Rh-catalyzed procedure. Moreover,
both of the boron atoms of bis(pinacolato)diboron (pinB)2 can
be employed in this C–H borylation reaction, whereas iridium
catalysis incorporates only one of the Bpin groupings.
As they are versatile precursors in many C–C bond formation
reactions including the Suzuki–Miyaura cross-coupling,
1-alkenylboron derivatives are an important class of compounds
in organic synthesis.1 Hydroboration of alkynes2 is one of the
most general methods for the preparation of 1-alkenylboron
compounds. However, this method has inherent limitations. For
example, cyclic 1-alkenylboron reagents generally are not
synthesized by this method due to the need for the corresponding
cyclic alkynes. Instead these compounds are often prepared by
transmetalation of 1-alkenyllithium (or Grignard) reagents with
trialkylborates,3 or via palladium-catalyzed cross-coupling
between 1-alkenylhalides or triflates with an appropriate
organoboron reagent.4 However, these reactions generally
require multistep preparation of the 1-alkenylmetal nucleophile
and/or the 1-alkenylhalide electrophile.
Dehydrogenative borylation of alkenes catalyzed by rhodium
complexes has been investigated extensively by Marder et al.6b
However, the reactions applied to cyclic alkenes are rare, and
thus our investigations began with the evaluation of a variety
of potential catalysts, i.e., combinations of phosphines and
rhodium complexes. Treatment of pinacolborane (2a) with
an excess of cyclohexene (1a) in the presence of a catalytic
amount of RhCl(PPh3)3 in THF at 115 1C afforded 1-alkenyl-
boronate ester 3a in 13% yield. Evaluation of other phosphines
in conjunction with [RhCl(cod)]2 (Table 1, entries 1–7)
revealed that Xantphos and DPEphos (entries 6–7) were
effective ligands and provided significant increases in yield.
The use of bis(pinacolato)diboron (2b) as a boryl reagent
instead of pinacolborane provided even better results
(entry 8).10 Toluene and ethereal solvents, except for 1,4-
dioxane, were suitable for this transformation (entries 9–14),
but acetonitrile and 1,2-dichloroethane were not (entries 15–16).
Heating at reflux or increasing in the amount of diboron
reagent 2b decreased the yield slightly (entries 17–18).
Impressive advances in transition metal-catalyzed functionali-
zation of arenes (replacement of aryl C–H with C–X, C–R, etc.)
have been made in recent years, particularly in the preceding
decade.5 In a similar vein, catalytic dehydrogenative borylation of
alkenes would provide an attractive alternative for the synthesis of
1-alkenylboron compounds.6–9 Although several catalytic systems
have been developed for this purpose, the substrates are mainly
limited to: ethylene, styrene derivatives, and 1,1-disubstituted
alkenes, i.e., a limited array of acyclic alkenes.6
We also examined RhCl(CO)(PPh3)2 as a catalyst precursor,
and this complex gave noticeably different results when
6b
(pinB)2 was used (eqn (1)). Surprisingly, allylboronate ester
3a0 was obtained as the major product (29%), along with the
desired 1-alkenylboronate ester (3a) as the minor product
(o5%). In addition, the 1-alkenyl product was not obtained
in the toluene–acetonitrile mixtures, which were previously
used for borylation of 1,1-disubstituted alkenes. The formation
of the undesired allylboronate 3a0 could be suppressed (o2%)
by using a catalyst derived from [RhCl(cod)]2–Xantphos.
Thus, this interesting effect of Xantphos in Rh catalysis is
one of the distinct differences between this catalyst system and
those developed previously for similar reactions.
Recently, Ishiyama and Miyaura et al. reported vinylic C–H
borylation of cyclic vinyl ethers with bis(pinacolato)diboron
catalyzed by iridium–dtbpy complex.8 In this reaction, the
substrates are limited to five-membered or six-membered cyclic
vinyl ethers. Olsson and Szabo have also recently reported a
´
tandem procedure consisting of an iridium-catalyzed, dehydro-
genative borylation of an unactivated cyclic alkene and a
subsequent palladium-catalyzed cross-coupling reaction.9
Herein, we describe a rhodium–Xantphos-catalyzed method
for the dehydrogenative borylation of alkenes that may offer
Massachusetts Institute of Technology, Department of Chemistry,
Cambridge, Massachusetts 02139, USA. E-mail: tfj@mit.edu;
Fax: +1 617 324 0253; Tel: +1 617 253 2135
w This article is part of a ChemComm ‘Catalysis in Organic Synthesis’
web-theme issue showcasing high quality research in organic
chemistry. Please see our website (http://www.rsc.org/chemcomm/
organicwebtheme2009) to access the other papers in this issue.
z Electronic supplementary information (ESI) available: Experimental
procedures. Data and spectra for new compounds (3e, 5d). See DOI:
10.1039/b921387b
ð1Þ
The substrate scope of this reaction is shown in Table 2.
Several cyclic alkenes (1a–e) undergo dehydrogenative
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Table 1 Exploratory rhodium-catalyzed dehydrogenative borylation
of cyclic alkenesa
Table 2 Investigation of substrate scope
Entry
Cycloalkene
3 (%)a
4 (%)a
1b
2
Cyclohexene (1a)
Cyclopentene (1b)
Cyclooctene (1c)
Cycloheptene (1d)
Norbornylene (1e)
64
54
75
63
61
7
9
12
8
21
Entry
2
Ligand (mol%)
Solvent
3a (%)b
3c
4
1
2
3
4
5
6
7
8
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
2b
2b
2b
2b
2b
2b
2b
2b
PPh3 (10)
PCy3 (10)
DPPB (5)
DPPF (5)
THF
THF
THF
THF
THF
THF
THF
THF
n-Bu2O
c-C5H9OMe
t-BuOMe
DME
1,4-Dioxane
Toluene
1,2-DCE
Acetonitrile
THF
7
2
6
21
9
41
41
54
56
51
61
55
20
49
0
5
a
Yields were determined by 1H NMR after column purification. See
b
the ESI for details.z Allylboronate ester 3a0 was obtained in 2%
rac-BINAP (5)
Xantphos (5)
DPEphos (5)
Xantphos (5)
Xantphos (5)
Xantphos (5)
Xantphos (5)
Xantphos (5)
Xantphos (5)
Xantphos (5)
Xantphos (5)
Xantphos (5)
Xantphos (5)
Xantphos (5)
c
yield. A trace amount of allylboronate ester 3c0 was observed.
9
10
11
12
13
14
15
16
17c
18d
cycle would be completed by s-bond metathesis between 10
and 2a or 2b, regenerating Rh complex 6.
0
41
48
This proposed mechanism also accounts for the observed
byproducts. The allylboronate esters (3a0 and 3c0, see Table 2)
would be furnished by the dissociation of complex 7, and the
reaction of rhodium hydride complex 10 with alkene 1 would lead
to the hydroboration product 4. In order to examine these
hypotheses, allylboronate ester 3a0 was treated with a large excess
of pinacolborane (2a) in the presence of the rhodium catalyst. In
accordance with the above prediction, isomerization of the double
bond occurred to yield vinylboronate 3a; 3a0 was completely
consumed. Direct formation of 3 from intermediate 8 via selective
deprotonation of the C–H bond a to the boronate ester is also
conceivable, and formation of norbornyl derivative (3e) would be
more easily explained by this pathway. Further investigation is
required to evaluate these and other hypotheses.
THF
a
Conditions: 1a (1.3 mmol), 2a (0.50 mmol) or 2b (0.25 mmol),
[RhCl(cod)]2 (0.013 mmol), THF (2.0 mL). Reactions were performed
in a Schlenk tube unless otherwise noted. Based on 1H NMR.
b
c
Dibenzyl ether was used as an internal standard. Performed in a
d
round bottom flask at reflux. Performed with 1.2 mmol of 1a and
0.50 mmol of 2b.
In summary, the dehydrogenative borylation reaction of
cyclic alkenes catalyzed by a rhodium–phosphine complex
provides an easy access to cyclic 1-alkenyl boron compounds,
a useful class of compounds.
borylation to form the corresponding 1-alkenylboronate
esters (3a–e) in good yields.11 In all cases, products of hydro-
boration 4a–e are also obtained in varying amounts, and for
this reason, we also examined a two-stage application of this
reaction (Scheme 1). After treatment of 1a, 1c and 1d with 2b
under dehydrogenative borylation conditions, the resulting
product mixtures were filtered through a thin layer of silica
and then subjected to Suzuki-Miyaura cross-coupling
conditions.4c The desired products (5a–d) were obtained in
moderate-to-good yield.
At this stage of our investigations, the mechanism of this
reaction is unclear, but we propose the sequence of events
shown in Scheme 2. Initial oxidative addition of a Rh complex
into the B–B bond would afford diboryl rhodium species 6.
Alkene insertion and b-hydride elimination would provide
rhodium-allylboronate complex 8. Isomerization to the major
product likely would require dissociation, re-complexation,
and hydrometalation to give 9. Subsequent b-hydride elimination
would then give the alkenylboronate ester product (3), along
with a rhodium hydride complex such as 10. The catalytic
Scheme 1 Suzuki–Miyaura cross-coupling reaction.
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3 N. Miyaura and K. Maruoka, in Synthesis of Organometallic
Compounds, ed. S. Komiya, Wiley, Chichester, UK, 1997,
p. 345.
4 (a) K. L. Billingsley and S. L. Buchwald, J. Org. Chem., 2008, 73,
5589–5591; (b) K. L. Billingsley, T. E. Barder and S. L. Buchwald,
Angew. Chem., Int. Ed., 2007, 46, 5359–5363; (c) J. Takagi,
K. Takahashi, T. Ishiyama and N. Miyaura, J. Am. Chem. Soc.,
2002, 124, 8001–8006; (d) K. Takahashi, J. Takagi, T. Ishiyama
and N. Miyaura, Chem. Lett., 2000, 126–127; (e) P. R. Eastwood,
Tetrahedron Lett., 2000, 41, 3705–3708.
5 For selected papers on the borylation of aromatic C–H bonds with
bis(pinacolato)diboron, see: (a) T. M. Boller, J. M. Murphy,
M. Hapke, T. Ishiyama, N. Miyaura and J. F. Hartwig, J. Am.
Chem. Soc., 2005, 127, 14263–14278; (b) T. Ishiyama, J. Takagi,
J. F. Hartwig and N. Miyaura, Angew. Chem., Int. Ed., 2002, 41,
3056–3058; (c) T. Ishiyama, J. Takagi, K. Ishida, N. Miyaura,
N. R. Anastasi and J. F. Hartwig, J. Am. Chem. Soc., 2002, 124,
390–391; (d) J.-Y. Cho, M. K. Tse, D. Holmes, R. E. Maleczka Jr.
and M. R. Smith III, Science, 2002, 295, 305–308; (e) C. N. Iverson
and M. R. Smith III, J. Am. Chem. Soc., 1999, 121, 7696–7697.
6 (a) N. Miyaura, in Catalytic Heterofunctionalization, ed. A. Togni
and H. Grutzmacher, Wiley-VCH, Weinheim, Germany, 2001,
¨
p. 10; (b) I. A. I. Mkhalid, R. B. Coapes, S. N. Edes,
D. N. Coventry, F. E. S. Souza, R. LI. Thomas, J. J. Hall,
S.-W. Bi, Z. Lin and T. B. Marder, Dalton Trans., 2008,
1055–1064, and references therein; (c) T. Ohmura, Y. Takasaki,
H. Furukawa and M. Suginome, Angew. Chem., Int. Ed., 2009, 48,
2372–2375.
7 A. Caballero and S. Sabo-Etienne, Organometallics, 2007, 26,
1191–1195.
8 (a) T. Kikuchi, J. Takagi, H. Isou, T. Ishiyama and N. Miyaura,
Chem.–Asian J., 2008, 3, 2082–2090; (b) T. Kikuchi, J. Takagi,
T. Ishiyama and N. Miyaura, Chem. Lett., 2008, 37, 664–665.
Scheme 2 Proposed reaction mechanism.
This work was supported in part by the National Institute of
General Medical Sciences (GM-63755). We thank Li Li (MIT)
for mass spectrometry data and the Japan Society for the
Promotion of Science for fellowship support for A. K.
Notes and references
´
9 V. J. Olsson and K. J. Szabo, Angew. Chem., Int. Ed., 2007, 46,
6891–6893.
1 (a) A. Suzuki, J. Organomet. Chem., 1999, 576, 147–168;
(b) N. Miyaura and A. Suzuki, Chem. Rev., 1995, 95, 2457–2483.
2 (a) K. Smith and A. Pelter, in Comprehensive Organic Synthesis,
ed. B. M. Trost, Pergamon Press, Oxford, UK, 1991, vol. 8, p. 703;
(b) T. Ohmura, Y. Yamamoto and N. Miyaura, J. Am. Chem. Soc.,
2000, 122, 4990–4991; (c) I. Beletskaya and A. Pelter, Tetrahedron,
1997, 53, 4957–5026; (d) X. He and J. F. Hartwig, J. Am. Chem.
Soc., 1996, 118, 1696–1702; (e) S. Pereira and M. Srebnik,
Organometallics, 1995, 14, 3127–3128.
10 DPEphos with (pinB)2 provided similar results to Xantphos.
11 Under the same reaction conditions, the acyclic internal alkenes
cis-4-octene and trans-4-octene afforded a complex mixture of
products. The reactions of substituted cyclic alkenes such as
1-methylcyclohexene and 3-methylcyclohexene also gave
a
complex mixture of the products, and a-methylstyrene and
methylenecyclohexene provided the corresponding products in
moderate yields (60% and 40%, respectively).
ꢀc
This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 907–909 | 909