Palladium-catalyzed carboboration: Borylative coupling of alkynes with alkenes through activation of boron-chlorine bonds

Article abstract of DOI:10.1246/cl.130131

Alkynes tethered to a chloro(diisopropylamino)boryl group undergo palladium-catalyzed borylative coupling with styrenes and acrylates, giving substituted cyclic 1,3-dienylboronic acid derivatives in a stereoselective fashion.

Full text of DOI:10.1246/cl.130131

doi:10.1246/cl.130131
538
Published on the web May 5, 2013
Palladium-catalyzed Carboboration: Borylative Coupling of Alkynes with Alkenes
through Activation of Boron-Chlorine Bonds
Kanayo Nakada, Masaki Daini, and Michinori Suginome*
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering,
Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510
(Received February 18, 2013; CL-130131; E-mail: suginome@sbchem.kyoto-u.ac.jp)
Alkynes tethered to a chloro(diisopropylamino)boryl group
B
Pd catalyst
base
undergo palladium-catalyzed borylative coupling with styrenes
and acrylates, giving substituted cyclic 1,3-dienylboronic acid
derivatives in a stereoselective fashion.
O
B
Cl
+
O
Scheme 1. Borylative coupling of alkyne and alkene.
Much effort has been devoted to the development of
catalytic borylations, because of the increasing demands for
organoboron derivatives in organic synthesis and drug discov-
ery.1 In addition to the simple substitutive borylation reactions
such as C-H borylation2 and C-X borylation,3 borylative C-
element bond formations,4 in which boron and additional
functional groups are concomitantly introduced across carbon-
carbon multiple bonds, attract increasing attention. Catalytic
hydroboration,5 diboration,6 and silaboration7 have been exten-
sively studied to establish efficient methods for the synthesis of
highly functionalized organoboronic acids.
Among such catalytic boron-element addition reactions,
carboboration is highly attractive in that C-C bonds are
concomitantly formed along with B-C bonds.8-10 Our initial
effort on carboboration has focused on the B-C addition
reactions, in which the B-C bond in cyanoborane or alkynyl-
borane is activated and adds to a carbon-carbon multiple
bond.11,12 More recently, we have been involved in the develop-
ment of transmetalative carboboration, in which activation of the
B-Cl bond by palladium or nickel catalyst is crucially involved
as the key elementary step.13,14 In this particular carboboration,
the organic groups are transferred from organozirconium as well
as organotin reagents. Although the transmetalative carbobora-
tion was synthetically useful, the requirement of stoichiometric
amounts of organometallic reagents detracts from its synthetic
merit. It may be more attractive if the organic groups are derived
from more easily accessible feedstock. Herein, we report new
palladium-catalyzed carboboration with use of alkene as the
source of organic group (Scheme 1). The reaction involves a
mechanism well related to the Mizoroki-Heck reaction,15 which
involves insertion of alkenes into a C-Pd bond of organo-
palladium intermediates.
Table 1. Palladium-catalyzed cyclizative carboboration of 1a
with styrene (2a)a
iPr2N
5 mol% Pd catalyst
Ph
B
NiPr2
B
10 mol% ligand
Cl
O
+
Ph
Ph
Ph
O
10 equiv
base
1a
2a
3aa
Entry Pd complex Ligand Base
Solvent T/°C %yieldb
1
2
3
4
5
6
7
8
9
[Pd(allyl)Cp] PPh3 Et3N
[Pd(allyl)Cp] PPh3 Et3N
[Pd(allyl)Cp] PPh3 Et3N
[Pd(allyl)Cp] PPh3 Et3N
[Pd(allyl)Cp] PPh3 Et3N
[Pd(allyl)Cp] PPh3 Et3N
Toluene 110
Dioxane 110
39
67
67
0
69
72
71
0
NMP
110
DMSO 110
CH3CN 110
CH3CN
80
80
80
80
80
80
80
80
80
80
80
80
[Pd(allyl)Cp] PPh3 K3PO4 CH3CN
[Pd(allyl)Cp] PPh3 Cs2CO3 CH3CN
[Pd(allyl)Cp]
®
Et3N
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
5
0
10 [Pd(allyl)Cp] PMe3 Et3N
11 [Pd(allyl)Cp] PCy3 Et3N
12 [Pd(allyl)Cp] PPh2Cy Et3N
13 [Pd(allyl)Cp] DPPE Et3N
14 Pd(OAc)2
15 [Pd(dba)2]
15
74
0
59
47
67
72
PPh3 Et3N
PPh3 Et3N
16 [PdCl2(PPh3)2] ®
17 [PdCl(allyl)] PPh3 Et3N
Et3N
aA mixture of chloroborane 1a (0.20 mmol), styrene (0.30
mmol), [Pd(allyl)Cp] (0.010 mmol), ligand (0.020 mmol), and
base (2.0 mmol) was heated under a nitrogen atmosphere.16
bNMR yield.
An alkyne-tethered chloroborane 1a, which was used in our
previous cyclizative carboboration with organozirconium and
-tin reagents,13a,13b was reacted with styrene under varied
reaction conditions (Table 1). Use of [Pd(allyl)Cp] as a reliable
precursor for the generation of Pd(0) species with triphenyl-
phosphine as a ligand allowed us to obtain the desired
carboboration product albeit in low yield at 110 °C in toluene
in the presence of triethylamine (Entry 1). We observed marked
solvent effect: dioxane, N-methylpyrrolidone (NMP), and ace-
tonitrile afforded acceptable reaction yields (Entries 2, 3, and 5),
whereas dimethyl sulfoxide (DMSO) failed to give product
(Entry 4). The reaction proceeded even at 80 °C in acetonitrile in
higher yield (Entry 6). We also examined effect of base on the
reaction yields to find triethylamine and potassium phosphate
were the bases of choice rather than cesium carbonate (Entries 7
and 8). The reaction hardly proceeded in the absence of
phosphine ligand (Entry 9). Upon screening the phosphine
ligands, we found that PPh3 and PPh2Cy gave good reaction
yields (Entries 6 and 12), while trialkylphosphines and bidentate
phosphines gave much inferior yields (Entries 10, 11, and 13).
We finally looked into the effect of precursor palladium
complexes. It turned out that, in addition to [Pd(allyl)Cp], we
could use other palladium sources, although the reaction yields
varied significantly (Entries 14-17). Note that the alkenylbora-
Chem. Lett. 2013, 42, 538-540
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www.csj.jp/journals/chem-lett/

539
iPr2N
Table 2. Palladium-catalyzed cyclizative carboboration of 1a
iPr2N
[Pd(π-allyl)Cp] (5%)
Ph
B
with alkenes 2a-2h followed by treatment with Ac2O and
Cl
PPh3 (10%)
O
B
+
pinacola
Ph
R
R
O
Et3N (10 equiv)
Me
Me
iPr2N
CH3CN, 80 °C
Me
iPr2N
[Pd(
π
-allyl)Cp] (5%)
2a (R = Ph)
Ph
1b
Me
B
Cl
PPh3 (10%)
2i (R = CO2Me)
O
B
+
3ba (R = Ph) 88%
R
R
Ph
O
3bi (R = CO2Me) 87%
Et3N (10 equiv)
CH3CN, 80 °C
OH
B
Ph
H2O
r.t.
1a
2
3
R
O
Ph
pinacol, Ac2O
DMAP, pyridine
Me
B(nip)
Me
5ba (R = Ph) 79%
5bi (R = CO2Me) 39%
R
THF, r.t.
AcO
4
Entry Alkene (R)
Time %yield of 3b %yield of 4c
Scheme 2. Palladium-catalyzed cyclizative carboboration of
1b with styrene (2a) and methyl acrylate (2i) followed by
hydrolysis.16
1
2
3
4
5
6
7
8
2a (Ph)
2b (p-MeOC6H4) 24 h
2c (p-EtO2CC6H4) 24 h
2d (p-ClC6H4)
2e (p-NCC6H4)
2f (1-naphthyl)
2g (2-pyridyl)
2h (n-C6H13)d
32 h
72 (3aa)
68 (3ab)
68 (3ac)
67 (3ad)
63 (3ae)
44 (3af)
48 (3ag)
26 (3ah)
70 (4aa)
62 (4ab)
63 (4ac)
61 (4ad)
53 (4ae)
37 (4af)
44 (4ag)
20 (4ah)
Ph
24 h
24 h
3 d
[Pd(PPh3)4] (5%)
NaOH (3.3 equiv)
Ph
Ph
Ph
5ba
+
Br
Me
Me
dioxane/H2O
50 °C, 3 h
5 d
2 d
OH
6 (99%)
aA mixture of chloroborane 1a (0.20 mmol), alkene (0.30
mmol), [Pd(allyl)Cp] (0.010 mmol), PPh3 (0.020 mmol), and
Et3N (2.0 mmol) was heated under a nitrogen atmosphere,
unless otherwise noted.16 bNMR yield. cIsolated yield.
d10 equiv.
Scheme 3. Cross-coupling of 5ba with trans-2-bromostyr-
ene.16
3aa
1a
Pd(0)
base
-H elimination
oxidative addition
of B–Cl
tion took place in a trans-addition fashion as observed in the
palladium- and nickel-catalyzed cyclizative carboboration using
organozirconium and organotin derivatives as transmetalation
agents.13a,13b We confirmed the stereochemistry by a NOE
measurement for the derivatized product 4aa.
iPr2N
iPr2N
Ph
Pd
Ph
Cl
B
B
Cl
O
Pd
O
Ph
D
A
Under the optimized reaction conditions, reactions of 1a
with various styrenes and an aliphatic alkene were carried out
(Table 2). Since the products were hydrolytically unstable, we
converted the primary products 3 into 4 by treatment with acetic
anhydride and pinacol in the presence of a catalytic amount of
DMAP with pyridine.11a,13a,13b Thus obtained 4 was isolated by
silica gel column chromatography. Styrenes bearing electron-
donating and -withdrawing functional groups at the para
positions successfully gave the corresponding products 4aa-
4ae (Entries 1-5). 1-Vinylnaphthalene (2f) and 2-vinylpyridine
(2g) afforded the corresponding carboboration products slug-
gishly in moderate yields (Entries 6 and 7). 1-Octene gave 4ah
albeit in low yield (Entry 8). Note that terminal and alkyl-
substituted alkynes did not give the corresponding products.
Use of the tert-alcohol-derived, alkyne-tethered chlorobo-
rane 1b afforded the corresponding cyclization product in higher
yields (Scheme 2). Reaction with styrene gave 3ba in 88%
yield. Moreover, use of 1b allowed reaction with methyl acrylate
(2i) in high yield, while 2i afforded the corresponding product
only in low yield (ca. 20%) in the reaction with 1a. These
products 3ba and 3bi obtained from tert-alcohol-derived 1b
were transformed into chromatographically stable 5 by hydrol-
ysis. Attempted treatment with pinacol/Ac2O failed to give the
corresponding acetylated products like 4. The half-ester-type
dienylboronic acid derivative 5ba was utilized in the Suzuki-
Miyaura coupling with 2-bromostyrene, giving a conjugated
triene product 6 in high yield (Scheme 3).17
insertion of alkyne
into B-Pd
insertion of C=C
into C-Pd
2a
iPr2N
iPr
iPr
Cl
Ph
Pd
N
B
Pd
B
Cl
O
cis-to-trans
isomerization
Ph
O
C
B
Scheme 4. Possible mechanism of palladium-catalyzed cycli-
zative carboboration of 1a with styrene (2a).
The mechanism of the cyclizative carboboration is assumed
to be as shown in Scheme 4. In the initial step, oxidative
addition of the B-Cl bond to palladium(0) phosphine species
takes place, giving a borylpalladium intermediate A.18 This B-
Cl bond activation leads to the intramolecular insertion of
carbon-carbon triple bond, giving alkenylpalladium intermedi-
ate B, in which the boron and palladium atoms are located in a
cis fashion.13b,18 A related alkenylpalladium intermediate was
isolated in our previous work on the transmetalative, cyclizative
carboboration.13b The intermediate B undergoes cis-to-trans
isomerization to C, because of the large steric repulsion between
the palladium moiety and the N-isopropyl group, which is
inevitably located in the same plane as the five-membered ring
due to the double bond nature of the B-N bond.13a The
Chem. Lett. 2013, 42, 538-540
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T. Kitano, N. Miyaura, Tetrahedron Lett. 1998, 39, 2357. d) T.
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intermediate C may be more reactive than B toward styrene,
which inserts into the carbon-palladium bond in a regioselective
manner to give D. The catalytic cycle ends up with ¢-hydride
elimination to form carboboration product 3aa with regeneration
of the palladium(0) species in the presence of base. These final
steps are mechanistically similar to the Mizoroki-Heck reaction,
where organopalladium intermediates undergo insertion into
their carbon-palladium bonds and subsequent ¢-hydride elim-
ination.15
In summary, we have demonstrated new catalytic carbobo-
ration in which the activation of B-Cl bond play a key role.
Although the scope of the reaction is still limited, the study
shows new possibilities of utilizing B-Cl bond activation in
catalysis for the synthesis of organoboronic acid derivatives.
7
This work is supported by Grant-in-Aid from MEXT.
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© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/