Alkenylation of allylic alcohols using alkenylboron dihalides: A formal transition-metal free Suzuki reaction

Article abstract of DOI:10.1039/b502026c

Carbon-carbon bond formation via substitution of an allylic hydroxide with stereodefined alkenyl groups using alkenylboron dihalides in the absence of transition metals. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b502026c

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Alkenylation of allylic alcohols using alkenylboron dihalides: a formal
transition-metal free Suzuki reaction{
George W. Kabalka,* Min-Liang Yao, Scott Borella and Zhongzhi Wu
Received (in Bloomington, IN, USA) 8th February 2005, Accepted 17th March 2005
First published as an Advance Article on the web 31st March 2005
DOI: 10.1039/b502026c
that the reaction proceeded through a 2-halovinyl(allyoxy)boron
halide intermediate A. The migration of the 2-halovinyl group
from boron to carbon then generated the final product. This led us
to investigate whether the migration of alkenyl groups could,
indeed, occur under these reaction conditions.17
Carbon–carbon bond formation via substitution of an allylic
hydroxide with stereodefined alkenyl groups using alkenyl-
boron dihalides in the absence of transition metals.
Transition-metal catalyzed allylic alkylation (especially asymmetric
alkylation, AAA) of allylic halides, carbonates, and carboxylates is
a very active topic in organic synthesis.1 Numerous studies have
been reported describing ligands2 and transition metal complexes3
designed to enrich the regio- and/or enantioselectivities of these
reactions. In this context, reactions with soft nucleophiles have
been well-studied. However, reactions involving hard nucleophiles
have not been developed as well due to the stability of the carbon–
metal bond in the transient p-allyl intermediates.4 To achieve
allylic substitution using hard nucleophiles, the transmetallation of
Grignard or organozinc reagents to the more reactive copper
reagents is often required.5,6 For organoboron nucleophiles,
transformation of boronic acids to more reactive lithium borates7
or zinc borates8 is generally required. Until now, only the coupling
of arylboronic acids with allylic halides,9 and carbonates9a,10 has
been described. For example, the RuCl3 catalyzed coupling of
allylic alcohols with arylboronic acids was recently achieved.11
Subsequently a successful sealed tube, Pd(PPh3)4 catalyzed
reaction was reported.12 Recently, Genet reported a [Rh(cod)Cl]2
catalyzed reaction of Baylis–Hillman adducts with arylboronic
acids.13 The reaction afforded formal Suzuki coupling products
through an unusual 1,4-addition/b-hydroxy elimination sequence.
Interestingly, the coupling of a vinyl group to an alcohol in the
absence of a transition metal has never been reported. Herein, we
wish to report the first transition metal free, formal Suzuki-type14
allylic alkenylation using allylic alcohols and alkenylboron
dihalides. From the point of organic synthesis, this novel allylic
alkenylation is quite attractive because it allows the attachment of
stereodefined alkenyl groups to an existing carbon skeleton. The
direct use of allylic alcohols as electrophiles makes the reaction
atom-efficient and more environmentally friendly.
The reaction shown in Scheme 2 was designed to probe the
feasibility of such an alkenyl group migration. Reaction of allylic
alcohol 1 and alkenylboron dihalide 2 in the presence of base
(BuLi or NaH) would generate intermediate B which is similar in
structure to the earlier proposed intermediate A. Based on the
suggested migration, Scheme 1, intermediate B should rearrange to
the desired product 3. It is well-known that the reaction of terminal
alkynes with one equivalent of boron trihalide generates the
stereodefined (Z)-2-halo-1-alkenylboron dihalide, 2, in quantitative
yield.18 Due to its readily availability 1,3-diphenyl-prop-2-en-1-ol
(1, R 5 R1 5 Ph) was chosen as a model compound to evaluate
the feasibility of the proposed alkenylation reaction. Fortunately,
in the presence of base (BuLi or NaH), the reaction proceeded
smoothly using (Z)-2-chloro-2-phenyl-1-alkenylboron dichloride at
room temperature19 and the desired product (Z,E)-1-chloro-1,3,5-
triphenyl-1,4-pentadiene (3a) was isolated in 83% yield. The
reaction is highly stereoselective. The resonances observed at
1
4.94 ppm (dd) in the H NMR spectrum and at 48.5 ppm in the
13C NMR spectrum demonstrate that only a single isomer forms
in the reaction.20
The method provides stereodefined 1,4-pentadienes starting
from readily available allylic alcohols. To evaluate the scope of this
new allylic alkenylation reaction, a variety of allylic alcohols 1 and
alkenylboron dihalides 2 were prepared and subjected to the
reaction. The results are presented in Table 1. For both
alkenylboron dichlorides and alkenylboron dibromides derived
from aryl alkynes, the reactions produce the expected products in
moderate to high yields. The isolated yields are somewhat lower
when alkenylboron dibromides are utilized. For alkenylboron
dihalides derived from aliphatic alkynes, the allylic alkenylation
reaction requires the use of alkenylboron dibromides.
Unsymmetrical allylic alcohols also produce pure products; no
regioisomers were detected by NMR analysis. Transition-metal
catalyzed allylic substitution reactions often afford mixtures of
regioisomers from the p-allylic intermediates.9,10 Further investiga-
tion revealed that substituents R and R1 are not limited to aryl
groups. In this respect, the new allylic alkenylation reaction is more
general than the reaction shown in Scheme 1. Interestingly, we
found that monosubstituted allylic alcohols do not lead to the
desired products.
We have focused on the chemistry of boron halide derivatives
for many years and have developed a number of novel reactions.15
Examples include the Grignard-like alkylation of aryl aldehydes
using alkylboron dihalides, and the BX3/PhBX2 mediated reac-
tions of styrene and aryl aldehydes leading to either 1,3-dihalo-1,3-
diarylpropanes or 3-halo-1,3-diarylpropanols. Recently we
reported a BX3 mediated reaction between aryl acetylenes and
aryl aldehydes (Scheme 1).16 Stereodefined 1,3,5-triaryl-1,5-
dichloro-1,4-pentadienes were isolated. At that time we proposed
{ Electronic supplementary information (ESI) available: experimental
section. See http://www.rsc.org/suppdata/cc/b5/b502026c/
*kabalka@utk.edu
In summary, we have developed a novel method to prepare
stereodefined 1-halo-1,3,5-substituted-1,4-pentadienes using readily
2492 | Chem. Commun., 2005, 2492–2494
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Scheme 1 Preparation of 1,4-dienes via boronate rearrangement.
Scheme 2 Preparation of 1,4-dienes via reaction of vinylboron dihalides with allyl alcohols.
Table 1 Allylic alkenylation of allylic alcoholsa
R
R1
R2
X
Productb
Yieldc(%)
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Ph
Ph
p-ClPh
H
Ph
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
Cl
Br
Br
Cl
Cl
Cl
Cl
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
—
—
83
81
78
79
65
61
71
68
p-MePh
m-FPh
p-ClPh
p-BrPh
o-FPh
Ph
p-MePh
n-C4H9
n-C8H17
m-FPh
m-FPh
Ph
62
65
77
58d
53d
66
Ph
(E)-PhCHLCH–
1-Naphthyl
Ph
Ph
Ph
Ph
47e
Trace
Trace
H
Ph
a
b
Reaction carried out in dry DCM at room temperature with n-BuLi as base. All products were characterized by NMR spectra and
c
elemental analyses (or HRMS). Isolated yields based on alkynes.
phenylpropenyl)napthalene was isolated.
d
e
NaH used as base. Approximately 15% of 1-(3-chloro-3-
available allylic alcohols and alkynes (the precursor to the
(Z)-alkenylboron dihalides). The reaction conditions are mild
and the reaction is highly stereo- and regioselective. Because the
reaction involves alkenylboron dihalides and the products are
identical to those obtained in Suzuki coupling reactions, this new
reaction can be viewed as a formal transition metal free Suzuki
reaction.
Notes and references
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Acknowledgement is made to the Donors of the American
Chemical Society Petroleum Research Fund for partial support of
this research. We also wish to thank the U. S. Department of
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George W. Kabalka,* Min-Liang Yao, Scott Borella and Zhongzhi Wu
Departments of Chemistry and Radiology, The University of Tennessee,
Knoxville, TN 37996-1600, USA. E-mail: kabalka@utk.edu;
Fax: +1-865-974-2997; Tel: +1-865-974-3260
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(1.5 mmol), and dry dichloromethane (8 mL) were combined in a
25 mL flask under a nitrogen atmosphere and stirred for 1 hour. In a
separate flask, the allylic alcohol (1.6 mmol) in dry dichloromethane
(8 mL) was treated with n-butyllithium (1.0 mL of a 1.6 M solution in
hexanes) at 0 uC and stirred at room temperature for 1 hour. The second
solution was then transferred to the first flask and the mixture allowed
to stir at room temperature overnight. Water (20 mL) was added and
the reaction mixture was extracted with ethyl acetate and dried over
anhydrous MgSO4. The solvents were removed in vacuo and the product
purified by silica gel column chromatography using hexane as an eluent.
20 At this time, the experimental evidence cannot be used to identify
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inversion, retention, or racemization. Analogous studies involving chiral
benzylic alcohols (unpublished results) strongly support the formation of
cationic intermediates which would lead to epimerization at the
migration terminus. Further studies using chiral allylic alcohols are
underway.
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2494 | Chem. Commun., 2005, 2492–2494
This journal is ß The Royal Society of Chemistry 2005