Direct introduction of a naphthalene-1,8-diamino boryl [B(dan)] group by a Pd-catalysed selective boryl transfer reaction

Article abstract of DOI:10.1039/c5cc00231a

A non-symmetrical diboron reagent, B(pin)-B(dan), has been utilised in the Pd-catalysed borylation of aryl bromides and chlorides. Remarkably selective formation of aryl-B(dan) bonds is established. This represents a direct and efficient way to introduce masked boronic acids. The synthetic usefulness of this reaction is demonstrated in the preparation of boron-differentiated di- and polyboron compounds.

Full text of DOI:10.1039/c5cc00231a

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Direct introduction of a naphthalene-1,8-diamino
boryl [B(dan)] group by a Pd-catalysed selective
boryl transfer reaction†
Cite this: Chem. Commun., 2015,
51, 5656
Received 10th January 2015,
Accepted 17th February 2015
Liang Xu and Pengfei Li*
DOI: 10.1039/c5cc00231a
www.rsc.org/chemcomm
A non-symmetrical diboron reagent, B(pin)-B(dan), has been utilised in moiety being transferred selectively.6 In contrast, the direct
the Pd-catalysed borylation of aryl bromides and chlorides. Remarkably synthesis of aryl B(dan) from commercially available com-
selective formation of aryl-B(dan) bonds is established. This represents a pounds has been rarely studied. The only example of this type
direct and efficient way to introduce masked boronic acids. The was realized via C–H borylation using (dan)BH.7 However, the
synthetic usefulness of this reaction is demonstrated in the preparation reaction efficiency remained low. Moreover, the regioselectivity
of boron-differentiated di- and polyboron compounds.
of the C–H borylation was governed by steric effects; some
regioisomers were not accessible by the method. Consequently,
Organoboronic acids have gained broad research interest in we wanted to explore for a direct and general approach to the
synthetic chemistry, drug discovery and materials science. As masked aryl boronic acid derivatives.
synthetic building blocks, they can react with various functional
Recently, differentially protected diboron reagents have been
groups to construct new carbon–carbon or carbon–heteroatom applied in chemoselective transfer of the two boryl groups to various
bonds.1 On the other hand, their high reactivity complicates the unsaturated bonds. For example, Santos and co-workers have
chemical selectivity in complex molecule synthesis. Consequently, demonstrated that sp2-hybridized boron of the sp2–sp3 hybridized
practical and readily removable masking groups which render boryl diboron reagents is selectively transferred in the copper-
groups temporarily inert have undergone great development in the catalyzed b-boration of a,b-unsaturated carbonyl compounds.8
last decade,2 especially in the fields of iterative cross-coupling3 and The sp2–sp2 hybridized non-symmetrical diboron reagent B(pin)-
functionalised polyboron compounds.4
B(dan) has recently been applied in the addition reactions of
The masked boronic acids are commonly synthesized from alkenes and alkynes, with the B(dan) moiety transferred selectively
the corresponding free boronic acids by condensation with (1a and 1b, Scheme 1) as mentioned above.6 Mechanistically, in both
masking molecules such as 1,8-diaminonaphthalene (dan) and cases, the cause of such selectivity was proposed to be the preferred
N-methyliminodiacetic acid (MIDA). Although proven successful
in many cases, this approach can be troublesome when the starting
organoboronic acids are not readily available or unstable. Therefore
a direct way to introduce the masked boryl group into simple
molecules is more desirable. Suginome and co-workers reported
the direct synthesis of alkenyl-B(dan) via C–H borylation5 or
hydroboration of alkynes3e with 1,8-naphthalenediaminatoborane
((dan)BH). The diboration of alkynes using a non-symmetrical
diboron reagent, B(pin)-B(dan), was disclosed by the same group
in 2010.4d More recently, alkyl and alkenyl 1,8-diaminonaphthalene
boronates have been synthesized by hydroboration of alkenes or
alkynes using B(pin)-B(dan) with the less Lewis acidic B(dan)
Center for Organic Chemistry, Frontier Institute of Science and Technology (FIST)
and Frontier Institute of Chemistry, Xi’an Jiaotong University, 99 Yanxiang Road,
Xi’an, Shaanxi, 710054, China. E-mail: lipengfei@mail.xjtu.edu.cn
† Electronic supplementary information (ESI) available: Experimental and spectro-
Scheme 1 Selective boryl transfer of a non-symmetrical diboron reagent.
scopic data for all compounds. See DOI: 10.1039/c5cc00231a
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interaction between the more Lewis acidic B(pin) moiety with basic
With the optimized reaction conditions in hand, we next
promoting reagents or catalysts. During our study on preparation of explored the substrate scope of this selective boryl transfer
functionalised polyboron reagents, we wondered whether a similar reaction. As shown in Scheme 2, various aryl bromides bearing
chemoselective borylation might be used for direct introduction of electron-withdrawing and -donating groups at the para- or
B(dan) into arenes by Miyaura-type borylation reaction.9 In classical meta-positions were borylated in good to excellent yields (for
Miyaura borylation of aryl halides, [LPd(Ar)OAc] is considered as the 2a–2l). It should be mentioned that free phenolic hydroxyl
key intermediate which then undergoes a transmetalation process groups (for 2g) and amino groups (for 2h) were well tolerated
with diboron reagents. We envisioned that under Miyaura-type in the reaction system, while the corresponding free aryl boronic
conditions, B(pin)-B(dan) may undergo a selective transmetalation acids bearing these two groups were usually prepared only in
process with [LPd(Ar)OAc] because of the stronger interaction moderate yields. Therefore the current method, involving the direct
between the Lewis basic-OAc and the more Lewis acidic B(pin) formation of C–B(dan) bonds from C–X bonds, is more practical and
moiety, generating the [LPd(Ar)B(dan)] intermediate preferentially efficient than the previous condensation route. This borylation
(1c, Scheme 1). The following reductive elimination would then reaction was found to be sensitive to the steric hindrance; elevated
selectively form the final borylation product ArB(dan). This might reaction temperature (100 1C) was necessary to give satisfactory yields
provide a straightforward method to synthesise aryl-B(dan) from for ortho-substituted aryl bromides (for 2m–2o). Aryl triflate (for 2q)
readily available aryl (pseudo)halides.
could also be converted into aryl-B(dan) directly. In addition,
With this in mind, we initiated our studies by examining
the reaction between B(pin)-B(dan) and 4-bromotoluene under
Pd-catalysed conditions. In a preliminary experiment, using a
catalytic combination of Pd2(dba)3 (2 mol%) and PPh3 (6 mol%)
(entry 1, Table 1), to our delight, the desired aryl-B(dan) product 2a
1
could be obtained in 19% yield based on H NMR analysis of the
crude product. Further screening of phosphine ligands afforded
more efficient conditions. Thus, when the reaction was conducted
at 100 1C for 12 hours using XPhos, a bulky monophosphine
ligand,9c,10 as the supporting ligand, the desired product could be
obtained quantitatively (entry 5). Similar to the classical Miyaura
borylation reaction, KOAc was found to be the best base for this
system. The reaction temperature could be decreased to 60 1C
without loss of yield (entry 9). However, further decreasing the
temperature led to dramatically lower yields (entries 7 and 8).
Omitting the Pd catalyst and the ligand, no desired product could
be observed (entry 11), and therefore a metal-free borylation path-
way was not working for this system.
Table 1 Optimization of reaction parametersa
Entry
Ligand
Base
T (1C)
Yieldsb (%)
1
2
3
4
5
6
7
8
PPh3
KOAc
KOAc
KOAc
KOAc
KOAc
KOtBu
KOAc
KOAc
KOAc
KOAc
KOAc
80
100
100
100
100
100
r.t.
50
19
20
95
29
99
Trace
18
tBu-XPhos
SPhos
XantPhos
XPhos
XPhos
XPhos
XPhos
XPhos
XPhos
—
76
9
60
60
60
99(98)e
64
10c
11d
N.R.
Scheme 2 Substrate scope of Pd-catalysed selective boryl transfer.
a
Reaction conditions: aryl halide (0.30 mmol), B(pin)-B(dan) (0.25 mmol),
a
Reaction conditions: 4-bromotoluene (0.12 mmol), B(pin)-B(dan) (0.10 mmol),
1,4-dioxane (0.5 ml) under a N2 atomosphere. b Yields based on 1H NMR
analysis of the crude products with 1,3,5-trimethoxybenzene added as an
internal standard. c 4 mol% Pd(OAc)2 was used as a catalyst. d The catalyst
and the ligand were not added. e Isolated yield shown in parenthesis.
1,4-dioxane (1.0 ml) under a N2 atomosphere. b Isolated yields based on the
c
amount of B(pin)-B(dan) used. The aryl chlorides and ortho-substituted
aryl bromides were borylated at 100 1C. Other cases mentioned were all
borylated at 60 1C.
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aryl chlorides were also utilized in this reaction, although they
generally needed a higher reaction temperature (100 1C) than
their bromide analogues (for 2a, 2d, 2i and 2s).
Following our previous work on the synthesis and applications of
differentiated polyboron reagents, we applied the present reaction in
facile preparation of polyboron compounds containing the B(dan)
group.4i,j Two routes were utilized toward the synthesis of these
compounds. The first one was starting from monoboron aryl halides
using selective naphthalene-1,8-diamino borylation to introduce the
B(dan) group. Thus, diboron compounds 3a–3c were conveniently
prepared in good yields (Scheme 3A). To the best of our knowledge,
there has been no literature precedence on compounds containing
both B(dan) and B(MIDA) groups. The second route was using
functionalised aryl B(dan) compounds as the starting materials
and various known borylation methods to introduce a different type
of boronyl group (Scheme 3B). For example, Rh-catalyzed borylation
of 2d via C–C bond cleavage under the literature conditions pro-
duced 3d containing a neopentanediolato boronyl group B(neop).11
A Cu-catalysed hydroboration of an alkene moiety also quantitatively
furnished diboron reagent 3e incorporating an alkyl B(pin) group.
Making use of the relative inertness of the B(dan) group,
we then assessed the possible utility of the above-prepared
functionalised aryl B(dan) compounds.12 The para-naphthalene-
1,8-diamino boryl aniline 2f was subjected to a chemoselective
Pd-catalysed Buchwald–Hartwig coupling13 with bromobenzene
and amination product 4 could be obtained in 75% yield without
interference from Suzuki–Miyaura type reaction. Much as antici-
pated, the reactivities of B(MIDA) and B(dan), the two effective
protecting groups for boronic acids on 3c, could also be
Scheme 4 Chemoselective transformations of functionalised aryl B(dan)
compounds.
Scheme 5 The synthesis of trisboronylbenzene.
differentiated in Suzuki–Miyaura coupling under aqueous basic
conditions, affording 5 in good yield (Scheme 4).
At last, taking advantage of the Ir-catalysed C–H borylation
process developed by our group and the methodology reported
herein, a 1,3,5-trisboronyl benzene was synthesized in three steps
from commercially available 3-chlorophenylboronic acid, with
these boronyl groups different from each other (Scheme 5). As far
as we know, this represents the first example of assembling three
different boronyl groups onto the same molecule. This new type of
organoboron reagents should be useful building blocks in modular
synthesis of multi-functionalised arene compounds.
In conclusion, by employing the non-symmetrical diboron
compound, B(pin)-B(dan), as the borylating reagent in Pd-catalysed
Miyaura-type reaction, we have realized the chemoselective B(dan)
moiety transfer to various aryl rings, yielding masked boronic
acids directly from abundant and cheap aryl halides. We have also
demonstrated the usefulness of this naphthalene-1,8-diamino
borylation in the facile preparation of boron-differentiated
di- and polyboron compounds and other functionalised aryl
boron compounds.
We are grateful for financial support from the National
Science Foundation of China (No. 21202129 and 21472146) and
the Ministry of Science and Technology of PRC (973 program for
young scientists, No. 2014CB548200).
Notes and references
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preparing boron-differentiated diboron compounds.
5658 | Chem. Commun., 2015, 51, 5656--5659
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