Boron-selective biaryl coupling approach to versatile dibenzoxaborins and application to concise synthesis of defucogilvocarcin M

Article abstract of DOI:10.1021/ol5031734

An efficient synthetic method for versatile dibenzoxaborins based on boron-selective Suzuki-Miyaura cross-coupling between o-borylphenols and aryl halides or triflates bearing a 1,8-diaminonaphthalene-protected o-boryl group is reported. A short synthesis

Full text of DOI:10.1021/ol5031734

Letter
pubs.acs.org/OrgLett
Boron-Selective Biaryl Coupling Approach to Versatile
Dibenzoxaborins and Application to Concise Synthesis of
Defucogilvocarcin M
Yuto Sumida,†,§ Ryu Harada,† Tomoe Kato-Sumida,†,§ Kohei Johmoto,‡ Hidehiro Uekusa,‡
and Takamitsu Hosoya*,†
†Laboratory of Chemical Bioscience, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10
Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan
‡Department of Chemistry and Materials Science, Graduate School of Science and Engineering, Tokyo Institute of Technology,
2-12-1, Ookayama, Meguro-ku, Tokyo, 152-8551, Japan
S
* Supporting Information
ABSTRACT: An efficient synthetic method for versatile
dibenzoxaborins based on boron-selective Suzuki−Miyaura
cross-coupling between o-borylphenols and aryl halides or
triflates bearing a 1,8-diaminonaphthalene-protected o-boryl
group is reported. A short synthesis of defucogilvocarcin M was
achieved using the proposed method in combination with
several other boron-mediated transformations.
Scheme 1. Synthetic Plan of Dibenzoxaborins based on
rganoboron compounds play valuable roles in a variety of
Boron-Selective Suzuki−Miyaura Cross-coupling
O
disciplines, e.g., as efficient building blocks in organic
synthesis and materials science and as unique pharmacophores
and chemosensors in medicinal chemistry and chemical biology.1
Recently, considerable attention has been paid to cyclic boronic
half esters, such as 1,3-dihydro-1-hydroxy-2,1-benzoxaborole
(1), because of their superior properties in terms of binding
affinity to saccharides2 and bioactivity.3 6-Hydroxy-6H-dibenz-
[c,e][1,2]oxaborin (2a),4 which is referred to as dibenzoxaborin
in this paper, is a cyclic boronic half ester that serves as a useful
building block for constructing versatile π-conjugated systems.5
Typically, dibenzoxaborins have been prepared by treatment of
2-hydroxybiaryl with BCl3 followed by addition of AlCl34a,b,5a or
a monohalogen−lithium exchange reaction of 2,2′-dibromobiar-
yl followed by treatment with a trialkyl borate.5b However, only
limited dibenzoxaborins are available from the reported synthetic
methods,4−6 and the utility of dibenzoxaborins remains largely
unexplored. Herein, we show an efficient synthetic method for
dibenzoxaborins that is based on boron-selective Suzuki−
Miyaura cross-coupling.
assumed that this strategy would be suitable for preparing diverse
dibenzoxaborins because the oxygen source 3 could be
transformed into triflate-type boron source 4 (X = OTf) by a
simple two-step procedure: dan-protection of the boryl group
and triflylation of the phenolic hydroxy group.
After extensive screening of the reaction conditions for cross-
coupling of (2-hydroxyphenyl)boronic acid (3a) with dan-
protected ortho-borylphenyl triflate 4a, an excellent result was
obtained using CyJohnPhos8b,9 as a ligand for the catalytic
system and potassium phosphate as a base (Scheme 2).10,11
Contrary to our expectation, the originally intended cross-
coupling product 5a was not obtained; however, the desired
dibenzoxaborin 2a was produced directly without special
manipulations. This result was possibly because of the high
affinity of oxygen for boron, which assisted deprotection of the
dan group and formation of a stable dibenzoxaborin skeleton.
Furthermore, we observed that using an equimolar amount of
Dibenzoxaborins 2 contain a biphenyl substructure; therefore,
we conceived the idea of preparing 2 using Suzuki−Miyaura
cross-coupling7 of ortho-hydroxyaryl boronic acid 3 with aryl
halide 4 bearing a 1,8-diaminonaphthalene (dan)-protected
ortho-boryl group,8 followed by deprotection of the dan group
and intramolecular dehydrative cyclization (Scheme 1). We
Received: October 31, 2014
Published: November 24, 2014
© 2014 American Chemical Society
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Organic Letters
Letter
Scheme 2. Optimized Conditions
Table 1. Scope of Substrates
base with an arylboronic acid was important to obtain
dibenzoxaborin in high yield.10 The reaction conditions using
an excess amount of base significantly decreased the product
yield accompanying the production of 2-phenylphenol, which
should be formed through protodeborylation of dibenzoxaborin
2a triggered by the redundant base.
Under the optimized conditions, a variety of O-sources 3 and
B-sources 4 with either electron-donating or -withdrawing
groups served as good substrates to afford dibenzoxaborins,
including those difficult to prepare by conventional methods
(Table 1). As for the oxygen source, not only boronic acids but
also boronic acid pinacol esters or a trifluoroborate salt12 were
usable under the same conditions (entries 1, 4−7, 12). In
particular, a Pd(PPh3)4 catalytic system gave better results for
some pinacol ester substrates (entries 1, 5, 6). These results
significantly increased the scope of the method because a variety
of o-hydroxyarylboronic acid pinacol esters can be readily
prepared in several ways: treatment of o-lithiated phenolates with
trialkyl borate,13 Pd-catalyzed Miyaura borylation of o-
halophenols,14 or iridium-catalyzed direct o-borylation of
phenols.15 In addition to aryl triflates, chlorides and bromides
with a neighboring Bdan group served as an efficient boron
source substrate (entries 8−11, 13−15). The method enabled
facile synthesis of disubstituted dibenzoxaborins and a
heteroatom containing compound, such as pyridine-fused
benzoxaborin 2m (entries 11−13). Unique pentacyclic arylbor-
onic ester 2n was also available via double cyclization of dibromo
boron source 4g using an excess amount of 3a (entry 14). The
planar structure of 2n was clearly demonstrated by X-ray
structure analysis.10,16 Coupling of olefinic boron source 4h with
3a proceeded in the same fashion, providing benzoxaborin 2o in
high yield (entry 15).
Moreover, trading the boryl group of the oxygen source with
the halogen group of the boron source was effective for the
synthesis of bis(dibenzoxaborin) derivative 2p with a binaphthyl
skeleton, which was achieved under modified conditions
(Scheme 3).10,17 Coupling of 3,3′-dibromo-[1,1′-binaph-
thalene]-2,2′-diol (6) with monodan-protected ortho-benzene-
diboronic acid pinacol ester 78b using di(1-adamantyl)-n-
butylphosphine18 as a ligand afforded 2p in moderate yield.10,19
The boron-selective coupling approach was also applicable to
the synthesis of dihydrodibenzazaborine20 derivatives using
ortho-borylated anilines as a nitrogen source (Scheme 4A).
Cross-coupling of (2-aminophenyl)boronic acid (8a) with 4a
under the general conditions afforded dihydrodibenzazaborine
95a,20a,b,d in 70% yield. The reaction of (2-(acetylamino)phenyl)
boronic acid (8b) with 4a afforded the cross-coupling product
10, wherein the Bdan group remained untouched. This was
probably due to the low nucleophilicity of amide nitrogen. In this
a
b
Bpin = 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl. Isolated yields.
Reaction times and yields for the reaction performed using Pd(PPh3)4
c
(5 mol %) and 2 M aqueous Na2CO3 (1.5 equiv) in DME at 90 °C in
parentheses. Molar ratio: 3a/4g/base = 3.0/1.0/1.5.
d
drated dimer 11 as the sole product in high yield (Scheme
4B).10,16,20c
The utility of the synthetic method for dibenzoxaborins was
demonstrated in a short synthesis of defucogilvocarcin M (12),
taking advantage of other boron-mediated transformations
21
case, the catalytic system using Pd(amphos)2Cl2 provided a
better result. Removal of the dan group of 10 under acidic
conditions and purification by recrystallization afforded dehy-
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Letter
regioselective [2 + 4]-cycloaddition of 3-benzyloxybenzyne
with 2-methoxyfuran.23 Recently, we have reported an efficient
generation method for arynes via ate complexes of arylboronic
esters bearing an ortho-triflyloxy group.24 This method was also
effective for the regioselective synthesis of naphthol 16 using
aryne precursor 15, which was easily prepared by ortho-
borylation15 of 2-benzyloxyphenol (13) and subsequent
triflylation. The boron source 4i was similarly prepared by
ortho-borylation and triflylation of 4-methylguaiacol (17),
followed by a simple two-step conversion of the pinacolatoboryl
group to the dan-protected boryl group (Scheme 5B).
Scheme 3. Bis(dibenzoxaborin) with Binaphthyl Skeleton
a
Scheme 4. Synthesis of Dihydrodibenzazaborines
Synthesis of defucogilvocarcin M was accomplished in three
additional steps (Scheme 5C). Boron-selective Suzuki−Miyaura
cross-coupling of 3i with 4i afforded the desired benzonaphtho-
borin 2q in 86% yield. Palladium-mediated deborylative CO
insertion of 2q provided dibenzocoumarin derivative 20.22l
Finally, debenzylation of 20 under reported conditions22l
afforded defucogilvocarcin M (12). The synthesis was
accomplished in 7 steps with a 39% overall yield in the longest
linear sequence, which compares very favorably with the previous
successful syntheses: 17% in 11 steps,22h 31% in 8 steps,22i 33% in
8 steps,22j 33% in 16 steps,22l and 15% in 9 steps22m (some of
them do not include the yields for the preparation of starting
materials).
a
amphos = p-(Me2N)C6H4P(t-Bu)2.
In summary, we have developed a convenient synthetic
method for diverse dibenzoxaborin derivatives. The method was
successfully applied to the concise synthesis of defucogilvocarcin
M. Further studies on dibenzoxaborins, including their
application to novel transformations and molecular recognition,
are currently in progress.
(Scheme 5). Defucogilvocarcin M is a representative aglycon of
the gilvocarcin-class antibiotics, which have been considered as a
challenging synthetic target by many groups.22 A previous report
has shown that dibenzoxaborin is capable of converting into 3,4-
benzocoumarin by a palladium-mediated deborylative CO
insertion reaction.5a Thus, we assumed that defucogilvocarcin
M with a dibenzocoumarin structure can be prepared from
benzonaphthoborin with appropriate substituents, such as 2q.
Therefore, we first prepared the coupling components, 2-boryl-
1-naphthol derivative 3i and triflate 4i.
ASSOCIATED CONTENT
■
S
* Supporting Information
The oxygen source 3i was prepared from known naphthol 1623
by iridium-catalyzed ortho-borylation15 (Scheme 5A). Previ-
ously, Suzuki and co-workers reported an efficient approach to
differentially protected 1,4,5-naphthalenetriol 16 based on
Experimental procedures and characterization data including
copies of NMR spectra and the X-ray crystallographic data. This
material is available free of charge via the Internet at http://pubs.
acs.org.
a
Scheme 5. Synthesis of Defucogilvocarcin M Using Boron-Mediated Transformations
a
cod = cyclooctadiene, dtbpy = 4,4′-di-tert-butyl-2,2′-bipyridyl.
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Letter
(7) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457. (b) Suzuki,
A.; Brown, H. C. Organic Syntheses via Boranes: Suzuki Coupling, Vol. 3;
Aldrich: Milwaukee, 2003.
(8) (a) Noguchi, H.; Hojo, K.; Suginome, M. J. Am. Chem. Soc. 2007,
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AUTHOR INFORMATION
■
Corresponding Author
*E-mail: thosoya.cb@tmd.ac.jp.
Present Address
§Chemical Biology Team, Imaging Chemistry Group, Division of
Bio-Function Dynamics Imaging, RIKEN Center for Life Science
Technologies (CLST), 6-7-3 Minatojima-minamimachi, Chuo-
ku, Kobe 650-0047, Japan.
(10) See Supporting Information for details.
(11) Attempts for coupling reaction using B sources without dan
protection were unsuccessful. See Supporting Information for details.
(12) (a) Molander, G. A.; Ellis, N. Acc. Chem. Res. 2007, 40, 275.
(b) Darses, S.; Genet, J.-P. Chem. Rev. 2008, 108, 288.
Notes
The authors declare no competing financial interest.
(13) Friedman, A. A.; Panteleev, J.; Tsoung, J.; Huynh, V.; Lautens, M.
Angew. Chem., Int. Ed. 2013, 52, 9755.
(14) Ishiyama, T.; Murata, M.; Miyaura, N. J. Org. Chem. 1995, 60,
7508.
(15) Boebel, T. A.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130, 7534.
(16) The X-ray crystallographic data for compounds 2n (CCDC
1020935) and 11 (CCDC 1020936) can be obtained free of charge from
the Cambridge Crystallographic Data Centre (CCDC) via www.ccdc.
cam.ac.uk/data_request/cif.
(17) Attempts for cross-coupling of 2-bromophenol with 7 resulted in
a low yield of 2a (approximately 10% yield) even with the use of any of
the catalytic systems including Pd(PPh3)4, Pd(OAc)2/CyJohnPhos,
Pd(OAc)2/P(1-Ad)2(n-Bu), and Pd[P(t-Bu)3]2.
(18) (a) Zapf, A.; Ehrentraut, A.; Beller, M. Angew. Chem., Int. Ed.
2000, 39, 4153. (b) Rueping, M.; Sugiono, E.; Steck, A.; Theissmann, T.
Adv. Synth. Catal. 2010, 352, 281.
(19) The cross-coupling of 3,3′-bis(pinacolatoboryl)-[1,1′-binaph-
thalene]-2,2′-diol with 4a (2 equiv) gave only a trace amount of 2p even
with the use of any of the catalytic systems such as Pd(PPh3)4,
Pd(OAc)2/CyJohnPhos, and P(1-Ad)2(n-Bu).
(20) (a) Dewar, M. J. S.; Kubba, V. P.; Pettit, R. J. Chem. Soc. 1958,
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ACKNOWLEDGMENTS
■
The authors thank Ms. Ayako Hosoya at Tokyo Medical and
Dental University for HRMS analyses, and Central Glass Co.,
Ltd. for their generous gift of Tf2O. This work was supported by
Platform for Drug Discovery, Informatics, and Structural Life
Science from MEXT, Japan; JSPS KAKENHI Grant Number
24651257 (T.H.); and the Terumo Life Science Foundation
(Y.S.).
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