Palladium-catalysed cross-coupling reaction of ultra-stabilised 2-aryl-1,3-dihydro-1H-benzo[d]1,3,2-diazaborole compounds with aryl bromides: A direct protocol for the preparation of unsymmetrical biaryls

Article abstract of DOI:10.3762/bjoc.10.109

There has been a significant interest in organoboron compounds such as arylboronic acids, arylboronate esters and potassium aryltrifluoroborate salts because they are versatile coupling partners in metal-catalysed cross-coupling reactions. On the other hand, their nitrogen analogues, namely, 1,3,2-benzodiazaborole-type compounds have been studied extensively for their intriguing absorption and fluorescence characteristics. Here we describe the first palladium-catalysed Suzuki-Miyaura cross-coupling reaction of easily accessible and ultra-stabilised 2-aryl-1,3-dihydro-1H-benzo[d]1,3,2-diazaborole derivatives with various aryl bromides. Aryl bromides bearing electron-withdrawing, electron-neutral and electron-donating substituents are reacted under the catalytic system furnishing unsymmetrical biaryl products in isolated yields of up to 96% in only 10 minutes.

Full text of DOI:10.3762/bjoc.10.109

Palladium-catalysed cross-coupling reaction of
ultra-stabilised 2-aryl-1,3-dihydro-1H-benzo[d]1,3,2-
diazaborole compounds with aryl bromides: A direct
protocol for the preparation of unsymmetrical biaryls
Siphamandla Sithebe and Ross S. Robinson*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2014, 10, 1107–1113.
Warren Laboratory, School of Chemistry and Physics, University of
KwaZulu-Natal, Private Bag X01, Scottsville, Pietermaritzburg 3209,
South Africa
doi:10.3762/bjoc.10.109
Received: 27 February 2014
Accepted: 14 April 2014
Published: 13 May 2014
Email:
Ross S. Robinson* - RobinsonR@ukzn.ac.za
Associate Editor: K. Itami
* Corresponding author
© 2014 Sithebe and Robinson; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
aryl bromide; 2-aryl-1,3-dihydro-1H-benzo[d]1,3,2-diazaborole;
asymmetrical biaryls; microwave; Suzuki–Miyaura cross-coupling
Abstract
There has been a significant interest in organoboron compounds such as arylboronic acids, arylboronate esters and potassium aryl-
trifluoroborate salts because they are versatile coupling partners in metal-catalysed cross-coupling reactions. On the other hand,
their nitrogen analogues, namely, 1,3,2-benzodiazaborole-type compounds have been studied extensively for their intriguing
absorption and fluorescence characteristics. Here we describe the first palladium-catalysed Suzuki–Miyaura cross-coupling reac-
tion of easily accessible and ultra-stabilised 2-aryl-1,3-dihydro-1H-benzo[d]1,3,2-diazaborole derivatives with various aryl bro-
mides. Aryl bromides bearing electron-withdrawing, electron-neutral and electron-donating substituents are reacted under the
catalytic system furnishing unsymmetrical biaryl products in isolated yields of up to 96% in only 10 minutes.
Introduction
Arylboronic acids 1, arylboronate esters 2 and potassium and versatile cross-coupling reaction in the literature [6]. The
aryltrifluoroborate salts 3 (Figure 1) have received considerable use of organoboron compounds 1, 2 and 3 (Figure 1) as nucleo-
attention and have found a special place as mild and versatile philic coupling partners in the Suzuki–Miyaura cross-coupling
nucleophilic coupling partners for carbon–carbon bond-forming reaction is particularly attractive due to the non-toxicity of the
cross-coupling reactions [1-5]. Amongst them, the byproducts, the ease with which they are transmetalated and
Suzuki–Miyaura cross-coupling reaction of aryl halides/triflates their high stability towards air and moisture, which are the key
and organoboron compounds is one of the most documented features for coupling reactions [7].
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Beilstein J. Org. Chem. 2014, 10, 1107–1113.
Figure 1: Structures of organoboron compounds 1–3.
On one hand, structural diverse π-conjugated organic mole- similar to our compounds, however, these compounds
cules containing a three-coordinate boron moiety such as tri- {ArB(dan)} are used as protecting groups not as coupling part-
mesitylborane (4), arylalkynyldimesitylborane 5 and 2-aryl-1,3- ners [15,16]. During the course of our studies on the syntheses,
diethyl-1H-benzo[d]1,3,2-diazaborole 6 (Figure 2) are well crystal structures, fluorescence and theoretical characteristics of
known and have received considerable attention due to their 1,3,2-diazaborolane functionalised organic molecules, which is
interesting luminescence characteristics, fluoride ion sensing reported in details elsewhere [17], we were encouraged by the
abilities, emissive as well as electron-transporting properties high yields of 2-aryl-1,3-dihydro-1H-benzo[d]1,3,2-diaza-
[8-11]. Three-coordinate boron compounds are electron-poor borole compounds (Scheme 1), their solubility in various
and strong π-electron acceptors owing to the empty boron organic solvents and their high stability towards air and mois-
pz-orbital, which is capable of significant delocalisation when ture to investigate their reactivity in transition metal-catalysed
attached to an organic π-system [11]. These compounds exhibit cross-coupling reaction. These compounds could be left on a
an unusual stability because of the bulky aryl groups, such as bench top in a basic media for weeks without any noticeable
mesityl (2,4,6-trimethylphenyl) groups, which provide steric degradation [17]. Herein, we report the first palladium-
conjunction around the empty boron pz-orbital thereby catalyzed cross-coupling reaction of 2-aryl-1,3-dihydro-1H-
blocking the incoming nucleophile (Figure 2, compounds 4 and benzo[d]1,3,2-diazaborole compounds with aryl bromides in
5) [12]. Alternatively, three-coordinate boron compounds func- only 10 minutes.
tionalized with 1,3,2-benzodiazaborole units are greatly
stabilised by electron back-donation from the two nitrogen Results and Discussion
atoms to the empty boron pz-orbital (Figure 2, compound 6) As shown in Scheme 1, 2-aryl-1,3-dihydro-1H-benzo[d]1,3,2-
[13,14].
diazaborole compounds were easily prepared from aryl halides
7 via the reaction of an organomagnesium intermediate with
Despite their popularity in the organic community, their trialkylborate solution followed by complexation with
profound stability towards air and moisture, their ease with o-phenylenediamine (8) in a single pot (Scheme 1). Following
which they are accessible and their non-toxicity, these com- this procedure, the desired products were obtained in excellent
pounds have, to the best of our knowledge, never been used in yields (81–93%) (Scheme 1).
any transition metal-catalysed C–C bond formation reaction as
coupling partners except for their 2-alkyl/alkenyl-substituted Suzuki–Miyaura cross-coupling reaction
analogues [14]. We are aware of reports describing the To find optimal reaction conditions, we initially studied the
Suzuki–Miyaura cross-coupling reaction aryl diaminoborole reaction of bromobenzene (13a) with compound 9 in a toluene/
containing compounds {ArB(dan)} which are structurally water mixture under different conditions as a model reaction
Figure 2: Structure of π-conjugated three-coordinate organoboron compounds 4 and 5.
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Beilstein J. Org. Chem. 2014, 10, 1107–1113.
Scheme 1: Synthesis of 2-aryl-1,3-dihydro-1H-benzo[d]-1,3,2-diazaborole compounds 9–12.
(Table 1). Attempted cross-coupling reaction of compound 9 more bulky Pd(PPh3)4 as a catalyst was used (Table 1, entries, 3
with bromobenzene (13a), in the absence of both the ligand and and 5). The use of Pd(PPh3)2Cl2 as a catalyst in conjunction
a base, gave, as expected, zero conversion of the starting ma- with PPh3 as a ligand and K2CO3 or K3PO4·H2O as bases also
terials (Table 1, entry 1).
failed to optimise the reaction conditions (Table 1, entries 4, 6
and 12). This was attributed to the decomposition of
The addition of PPh3 as a ligand and K3PO4 as a base failed to Pd(PPh3)2Cl2 catalyst to Pd-black. Moderate to good yields
afford the desired coupled product in any substantive yield were obtained when of Pd(OAc)2/PCy3 or Pd(OAc)2/PPh3
(Table 1, entry 2). Poor conversion of the starting material and combinations were used (Table 1, entries 8–11). Pd(OAc)2/
low assay yield of the desired product were observed when PCy3 and K3PO4·H2O (Table 1, entry 9) was recognised to be
Table 1: Initial optimisation of reaction conditions.a
Entry
Pd cat.
Ligand
Base
Yields (%)b 13
1
2
PdCl2
PdCl2
none
PPh3
none
K3PO4
0
<5
21
18
10
33
<5
51
88
67
76
20
3
Pd(PPh3)4
Pd(PPh3)2Cl2
Pd(PPh3)4
Pd(PPh3)2Cl2
PdCl2
none
K2CO3
4
none
K2CO3
5
none
K3PO4·H2O
K3PO4·H2O
K3PO4·H2O
K2CO3
6
PCy3
7
PCy3
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd (PPh3)2Cl2
PPh3
9
PCy3
K3PO4·H2O
K3PO4
10
11
12
PCy3/PPh3c
PCy3
K2CO3
PPh3
K2CO3
aReaction conditions: compound 9 (0. 85 mmol), bromobenzene (13a, 0.77 mmol), Pd cat. (4 mol %), ligand (8 mol %), base (3 equiv), toluene
(0.50 mL) and water (0.1 mL). Closed vessel, 80 W of microwave energy, 100 °C, 100 psi of pressure, 10 minutes. bIsolated yields after column chro-
matography. c4 mol % each of the ligands.
1109

Beilstein J. Org. Chem. 2014, 10, 1107–1113.
the most effective combination and was thus chosen as optimal hindered ortho-substituted boronate 11 generally afforded lower
reaction conditions for the purpose of this study. With the opti- yields when compared to other boronate derivatives (Table 2,
mized reaction conditions in hand, the scope and the limitations entries 5 and 6). This was attributed to incomplete conversion
of the cross-coupling reaction was investigated using of the starting materials possibly due to a steric effect around
bromobenzene (13a) and 4-bromoanisole (13b) as elelctrophilic the boron atom which is consistent with the literature [6,18,19].
coupling partners and boronates 9–12 (Scheme 1) as the corres- The cross-coupling of an electron-rich aromatic system
ponding nucleophilic coupling partners (Table 2). The cross- (4-bromoanisole) was generally less efficient compared to
coupling reaction of bromobenzene (13a) with boronates 9–12 bromobenzene (Table 2, entries 2 and 6). This effect was attrib-
went smooth affording the coupled products in yields ranging uted to the deactivation of the carbon–bromine bond as a result
from 68% to 88% (Table 2, entries 1, 3, 5 and 7). The sterically of electron-donating substituent (OMe) [20].
Table 2: Palladium-catalysed cross-coupling of boronate 9–12 with bromobenzene and 4-bromoanisole.a
Entry
1
Boronate
ArBr
Product
Yieldsb
88
14
13a
9
9
2
3
62
85
15
13b
13a
16
10
10
11
11
4
5
6
68
68
65
13b
13a
17
18
19
13b
1110

Beilstein J. Org. Chem. 2014, 10, 1107–1113.
Table 2: Palladium-catalysed cross-coupling of boronate 9–12 with bromobenzene and 4-bromoanisole.a (continued)
7
8
72
76
13a
20
21
12
12
13b
aReaction conditions: Boronate 9–12 (1.1 eqiuv), 13a and 13b (1.0 equiv), Pd(OAc)2 (4.0 mol %), PCy3, (8.0 mol %), K2PO4·H2O (3.0 equiv), toluene
(0.50 mL) and H2O (0.10 mL), 80 W of microwave energy, 100 °C, 100 psi, 10 minutes. bYields of isolated products after a flash column chromatog-
raphy.
Encouraged by our results (Table 2), we then turned our atten- of electron-deficient electrophiles (4-bromoacetophenone (13d)
tion to investigate the reactivity of activated as well as conju- and 4-bromonitrobenzene (13c)) furnished the desired coupled
gated electrophiles in our catalytic system (Table 3). Unlike products in excellent yields ranging from 85 to 96% (Table 3)
bromobenzene and 4-bromoanisole, the cross-coupling reaction [6,21]. These observations are consistent with the literature and
Table 3: Palladium-catalysed cross-coupling of boronate 9–12 with 4-bromonitrobenzene, 4-bromoacetophenone and 9-bromoantracene.a
Entry
Boronate
ArBr
Product
Yields (%)b
1
91
22
13c
9
9
2
3
90
96
23
24
13d
13c
10
4
5
94
85
13d
13c
25
26
10
11
1111

Beilstein J. Org. Chem. 2014, 10, 1107–1113.
Table 3: Palladium-catalysed cross-coupling of boronate 9–12 with 4-bromonitrobenzene, 4-bromoacetophenone and 9-bromoantracene.a
(continued)
6
86
91
27
28
13d
13c
11
12
12
9
7
8
86
75
29
13d
13e
9
30
31
10
72
13e
11
11
69
13e
12
32
aReaction conditions: boronate 9–12 (1.1 eqiuv), 13c–e (1.0 equiv), Pd(OAc)2 (4.0 mol %), PCy3, (8.0 mol %), K2PO4·H2O (3.0 equiv), toluene
(0.50 mL) and H2O (0.10 mL), 80 W of microwave energy, 100 °C, 100 psi, 10 minutes. bYields of isolated products after a flash column chromatog-
raphy.
are attributed to the activation of the carbon–bromine bonds due Sterically hindered boronate 10 was smoothly coupled with
to the electron-withdrawing functional groups. The presence of 4-bromonitrobenzene (13c) and 4-bromoacetophenone (13d)
an electron-withdrawing group induces oxidative addition of the providing coupled products 24 and 25 in 96 and 94% yields,
carbon–bromine bond to the metal centre (catalyst) compared to respectively (Table 3, entries 3 and 4). Although it is known
the corresponding electron-neutral and electron-rich functionali- that ortho-substituted boron counterparts usually suffer from
ties [22]. The cross-coupling reaction of boronate 9 with both facile protodeborination providing coupled products in low
substrates 13c and 13d afforded the desired products, as yields [5], ortho-substituted boronate 11 afforded the desired
expected, in high yields (Table 3, entries 1 and 2). We noticed products 26 and 27 in 85 and 86% yields, respectively (Table 3,
that steric hinderance on the boronate 10 did not have any nega- entries 5 and 6). The cross-coupling reaction of boronate 12,
tive impact on the cross-coupling reaction investigated herein. with each of the substrates (13c and 13d), furnished the desired
1112

Beilstein J. Org. Chem. 2014, 10, 1107–1113.
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Although arylboronic acids, arylboronate esters and potassium
aryltrifluoroborate salts are powerful coupling partners in the
Suzuki–Miyaura cross-coupling realm, extending the scope of
organoboron compounds that can participate effectively as
coupling partners in the cross-coupling reaction is still neces-
sary. We have synthesised a range of 2-aryl-1,3-dihydro-1H-
benzo[d]1,3,2-diazaborole compounds and developed their first
Pd-catalysed Suzuki–Miyaura cross-coupling reaction with a
range of aryl bromides bearing electron-rich, electron-neutral
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Supporting Information File 1
Detailed experimental procedures and copies of 1H and
13C NMR spectra of all synthesised compounds.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-10-109-S1.pdf]
Acknowledgements
We gratefully acknowledge NRF and the University of
KwaZulu Natal for financial assistance, and Mr Craig Gimmer
for NMR assistance.
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