Palladium-catalyzed addition of organoboronic acids to allenes

Article abstract of DOI:10.1039/b309258e

The palladium-catalyzed addition reaction of alkenyl- or aryl-boronic acids into various allenes is described, which allows C-C bond formation in a highly regioselective manner under very mild conditions.

Full text of DOI:10.1039/b309258e

Palladium-catalyzed addition of organoboronic acids to allenes
Chang Ho Oh,* Tae Won Ahn and Raghava Reddy, V.
Department of Chemistry, Hanyang University, Sungdong-Gu, Seoul 133-791, Korea.
E-mail: changho@hanyang.ac.kr; Fax: +82-2-2299-0762; Tel: +82-2-2290-0932
Received (in Corvallis, OR, USA) 4th August 2003, Accepted 27th August 2003
First published as an Advance Article on the web 17th September 2003
The palladium-catalyzed addition reaction of alkenyl- or
aryl-boronic acids into various allenes is described, which
allows C–C bond formation in a highly regioselective
manner under very mild conditions.
the presence of catalytic amounts of acetic acid afforded 3aa
with an excellent selectivity, albeit in low yields (entries 2 and
5). However, it was interesting to observe that the reaction in
1,4-dioxane worked nicely for most cases. The effect of Pd
complex and ligand on the catalytic activity was also investi-
gated. Both Pd(II) complexes such as Pd(OAc)2/2PPh3 and
Pd(OAc)2/dppb and the Pd(0) complex, Pd(PPh3)4, catalyze the
reaction smoothly. Gratifyingly, the use of Pd(PPh3)4 in 1,4
dioxane showed more promise resulting in the formation of
product 3aa in excellent overall yield (entry 3).
Subsequently we tested the generality of the reaction with
some commercially available boronic acids 2 to various allenes
1 (eqn. 2) and the results are summarized in Table 2. First of all,
we tested the addition reaction of various organoboronic acids
to the allene 1a. All reactions afforded the corresponding
addition products in good yields (entries 1–5). This addition
reaction occurs in a highly regioselective manner, with the
organic group on boronic acid adding to the middle carbon of
the allene moiety. However, fine tuning of the reaction
conditions is required for each boronic acid employed in order
to achieve high yield. It was of interest to investigate the
reactions of other substituted allenes (1b–j) with boronic acids
(2a–b) under these catalytic conditions of 3 mol% Pd(PPh3)4
and 10 mol% of AcOH in 1,4-dioxane.
Miyaura discovered the addition of organoboronic acids to a,b-
unsaturated ketones by a rhodium-phosphine complex in 1997.1
Since then, transition metal-catalyzed addition to unsaturated
bonds with organoboronic acids has been a subject of intensive
work in the area of organic and organometallic chemistry. Very
recently, we reported Pd-catalyzed hydroarylation which is
widely applicable to terminal as well as to internal alkynes.2
Allenes are a class of compounds with unique reactivities due
to the existence of two orthogonal p-bonds and they are very
useful intermediates in organic synthesis.3 Transition-metal
catalyzed reactions of allenes have attracted increasing interest
during the last two decades.4 However, to the best of our
knowledge reports on transition metal-catalyzed additions of
boronic acids to allenes is not known. On the other hand
conjugated addition to enones,5 addition to aldehydes,6 allylic
substitution,7 carbonylation8 and cross coupling reactions with
alkenes or acid chlorides9 are well known. In continuing
palladium-catalyzed allene chemistry,10 we wish to report here
an efficient regioselective palladium-catalyzed addition of
boronic acids to allenes under very mild conditions.
For our initial survey, we conducted the Pd-catalyzed
hydroalkenylation of allene 1a† with hexenylboronic acid (2a)
under a variety of conditions, where we expected to obtain a
mixture of stereoisomers of products 3aa and 4aa (eqn. 1).
(2)
Table 2 Pd-Catalyzed hydroalkenylation of allenes 1 with organoboronic
acids 2 in the presence of 10 mol% AcOH
(1)
Entry
Allenes
R2B(OH)2 T/°C
t/h
Products Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
1a
1a
1a
1a
1a
1b
1b
1c
1c
1d
1d
1e
1e
1f
2b
2c
2d
2e
2f
60
60
60
60
60
50
50
60
60
60
60
50
50
60
60
60
60
60
60
80
80
70
70
3
12
11
3
5
3
3
7
9
3
3
3
3
5
5
8
10
3
3
3ab
3ab
3ab
3ab
3ab
3ba
3bb
3ca
65
55
64
66
55
78
65
83
74
75
63
65
59
78
69
68
59
62
58
78a
63a
61a
From a series of studies, we found that the yield of product 3aa
depends greatly on the palladium catalyst as well as the reaction
solvent as summarized in Table 1. After we screened this
reaction in several solvents, the reaction in DMF or in THF in
2a
2b
2a
2b
2a
2b
2a
2b
2a
2b
2a
2b
2a
2b
2a
2b
2a
2b
Table 1 Pd-Catalyzed hydroalkenylation of allene 1a with organoboronic
acid 2a in the presence of 10 mol% AcOH
3cb
3da
3db
3ea
3eb
3fa
Catalyst
(3 mol%)
Entry
Solvent
T/°C
t/h
Yield (%)a
1
2
3
4
5
6
7
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(OAc)2/PPh3
Chloroform
DMF
1,4-Dioxane
Toulene
35
80
50
45
50
50
60
20
3
3
20
3
3
20
53
89
25
82
78
81
1f
3fb
3ga
1g
1g
1h
1h
1i
1i
1j
1j
3gb
3ha
3hb
3ia,4ia
3ib,4ib
3ja,4ja
THF
b
1,4-Dioxane
10
12
12
12
Pd(OAc)2/dppbc 1,4-Dioxane
3
a Isolated yields of the isomerically pure 3aa. b The catalyst was prepared
by mixing 3 mol% Pd(OAc)2 and 6 mol% of PPh3. c The catalyst was
prepared by mixing 3 mol% Pd(OAc)2 and 3 mol% of dppe.
3jb,4jb 57a
a The ratio of 3 and 4 was almost 1 : 1 in each case.
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Initially, we invesigated the reaction of monosubstituted
allenes (1b–f). The reaction of 1b with hexenyl boronic acid 2a
and phenyl boronic acid 2b afforded the addition products 3ba
and 3bb in 78 and 65% yields, respectively (entries 6 and 7).
Under similar reaction conditions, allenic nitrile (1c), allenic
ethylester (1d), allenol (1e), and allenal (1f) smoothly reacted
with boronic acids 2a and 2b gave the corresponding addition
products in good to excellent yields (entries 8–15). In all these
cases only one stereoisomer with (E)-configuration was ob-
served.
Fig. 2
In conclusion, we have demonstrated a new palladium-
catalyzed addition of alkenyl- and aryl-organoboronic acids to
various allenes. This reaction proceeds under mild conditions,
to provide E-tri-substituted dienes and styrenes in good to
excellent yields and with good regio- and stereo-control (in the
case of monosubstituted allenes).
We
thank
the
Korean
Research
Foundation
(2001-015-DP0334), Korea, and the Center of Molecular
Design and Synthesis (CMDS) for support of this research.
Raghava Reddy, V. is especially grateful for a graduate
fellowship supported by the BK21 project in 2003.
Notes and references
† General procedure: A 10 mL round-bottomed flask was charged with
tetrakis(triphenylphosphine)palladium(0) (7.6 mg, 0.0066 mmol), allenic
benzylether (1a, 38.3 mg, 0.22 mmol), hexenyl boronic acid (2a, 34 mg,
0.26 mmol) and 1,4-dioxane (1.0 mL) and then purged the system with a dry
argon atmosphere. The resulting mixture was treated with acetic acid (1.3
mL, 0.022 mmol) via a 10 mL GC syringe. This was then stirred at 50 °C for
3 h. On completion of the reaction, the mixture was allowed to cool to 0 °C,
quenched with water, and then extracted with ether. The organic portion was
washed with water and brine successively, dried over magnesium sulfate,
and concentrated in vacuo. The crude product was then purified by flash
chromatography (ethyl acetate/hexane = 1/10) to give the addition product
3aa (50.0 mg, 89%) as a colorless oil. All products 3aa–4jb have been
satisfactorily characterised by means of 1H NMR, 13C NMR, IR and
HRMS.
Under these conditions, two 1,1-disubstituted allenes (1g and
1h) afforded 1,3-butadiene derivatives 3ga and 3ha with
hexenylboronic acid 2a and styrene derivatives 3gb and 3hb
with phenyl boronic acid 2b in good yields (entries 16–19).
We were interested in extending this process to 1,3-dis-
ubstituted allenes (1i and 1j) and found that, unlike the other
allenes, these required higher temperature and longer reaction
time to proceed to completion. Notably, we have observed that
the corresponding reactions with boronic acids 2a and 2b
afforded a stereoisomeric mixture of products 3ia and 4ia, 3ja
and 4ja, 3ib and 4ib, and 3jb and 4jb, respectively (entries
20–23). The formation rate of these 1,3-disubstituted allenes
was greatly slowed probably due to the steric hindrance of the
allenes.
Here the catalytic reaction was highly regioselective with the
organic group on boronic acid adding to the middle carbon of
the allene moiety. We observed the formation of E-isomer
solely from the mono and 1,1-disubstituted allenes which was in
contrast to the fact that most carbopalladation reactions of
mono- and di-substituted allenes are reported to give E and Z
isomeric products with low selectivity.11 A plausible explana-
tion for the formation of the exclusive E-isomer is based on
face-selective addition of organoboronic acids to the allenes
(Fig. 1).
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dependent (260 to 30 °C) NOESY experiments with 150, 200,
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found between Ha and Hc and between Hb and Hd, while no such
NOE was found between Hc and Hd (Fig. 2) which clearly
shows a trans relationship.
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Fig. 1
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