Site-selective C-H borylation of quinolines at the C8 position catalyzed by a silica-supported phosphane-iridium system

Article abstract of DOI:10.1002/asia.201301423

Site-selective C-H borylation of quinoline derivatives at the C8 position has been achieved by using a heterogeneous Ir catalyst system based on a silica-supported cage-type monophosphane ligand SMAP. The efficient synthesis of a corticotropin-releasing f

Full text of DOI:10.1002/asia.201301423

COMMUNICATION
DOI: 10.1002/asia.201301423
À
Site-Selective C H Borylation of Quinolines at the C8 Position Catalyzed by
a Silica-Supported Phosphane–Iridium System
Shota Konishi,[a] Soichiro Kawamorita,[a] Tomohiro Iwai,[a] Patrick G. Steel,*[b]
Todd B. Marder,*[c] and Masaya Sawamura*[a]
À
À
Abstract: Site-selective C H borylation of quinoline deriva-
Herein, we report the Ir-catalyzed site-selective C H bor-
tives at the C8 position has been achieved by using a hetero-
geneous Ir catalyst system based on a silica-supported cage-
type monophosphane ligand SMAP. The efficient synthesis
of a corticotropin-releasing factor1 (CRF1) receptor antago-
ylation of quinoline derivatives with bis(pinacolato)diboron
(pinB–Bpin, 2). C8-selective borylation was effected by
choosing silica-supported trialkylphosphane (Silica-SMAP)
as a monodentate P ligand for Ir.[12–14] The borylation reac-
tion proceeded under mild reaction conditions with excel-
lent site selectivity toward various substrates with different
substitution patterns. Our synthesis of a corticotropin-releas-
ing factor1 (CRF1) receptor antagonist demonstrates the ro-
bustness and utility of this heterogeneous catalysis.[15]
À
nist based on a late-stage C H borylation strategy demon-
strates the utility of the C8 borylation reaction.
The quinoline heterocyclic scaffold is an important struc-
tural motif that is found in many natural products, bioactive
compounds, dyes, and other functional molecules, for exam-
ple, Alq3 for OLEDs.[1–3] Accordingly, the development of
efficient methods for accessing substituted quinolines is
a subject of considerable importance. In particular, stream-
lining the synthetic process through the introduction of site-
selective direct functionalization of a quinoline C H bond is
highly desirable. Several methods that allow direct C C
bond formation at the C2 position of quinolines or quinoline
N-oxides, using Rh,[4] Pd,[5] Ni,[6] Cu,[7] and Ag[8] catalyst sys-
tems, have been reported in recent years. The C2 selectivity
of these catalysts is based on the inherent reactivity of the
Miyaura, Ishiyama, and co-workers reported that boryla-
tion of quinoline occurred preferentially at the C3 position
when an Ir–bipyridine-type (Ir–dtbpy; Hartwig–Ishiyama–
Miyaura catalyst; dtbpy=4,4ꢀ-di-tert-butylbipyridine) cata-
lyst was used, with a large excess of the quinoline substrate
(10 equiv).[16] More recently, as part of our studies on the
[17]
À
À
C H borylation of arenes,
some of the authors of the
À
present work provided guidelines for achieving selective
borylation at the C3, C4, C6, or C7 positions of disubstituted
quinolines.[17j] In contrast, access to the much desired quino-
line-8-boronic acid has required multiple steps, which in-
volve generation of the corresponding halide as an immedi-
ate precursor.[18] The C8-selective borylation discussed here
circumvents these issues and complements the existing quin-
À
C=N bond or the N-adjacent C H bond. In contrast, site-se-
lective catalytic C H transformation at the C8 position,
À
À
which is also proximal to the N atom, has been reported, to
the best of our knowledge, only by Chang and co-workers.
In these studies, Rh–NHC (NHC=N-heterocyclic carbene)
catalytic systems were used for C8 arylation with aryl bro-
mides.[9–11]
oline C H activation methods.
The reaction of quinoline 1a (0.30 mmol) and diboron 2
(1.1 equiv) in methyl tert-butyl ether (MTBE) in the pres-
ence of an immobilized catalyst precursor (Ir, 2 mol%), pre-
pared in situ from Silica-SMAP, and [IrACHTNUGRTNENUG(OMe)ACHUTNGTREN(NUGN cod)]2 (P/Ir,
1:1; cod=cycloocta-l,5-diene) proceeded at 608C over 12 h
with 94% consumption of 1a. (Scheme 1). The 1H NMR
spectrum of the crude product indicated that the major
product was the C8-borylated quinoline 3a, which was con-
taminated with small amounts of the reduced products, such
as 1,2,3,4-tetrahydroquinoline (4a, 13% yield, analysis
[a] S. Konishi, Dr. S. Kawamorita, Dr. T. Iwai, Prof. Dr. M. Sawamura
Department of Chemistry, Faculty of Science
Hokkaido University, Sapporo 060-0810 (Japan)
E-mail: sawamura@sci.hokudai.ac.jp
[b] Prof. P. G. Steel
1
based on H NMR spectroscopy).[19] As the quinoline-8-bor-
Department of Chemistry
Durham University
South Road, Durham DH1 3LE (UK)
E-mail: p.g.steel@durham.ac.uk
onic acid pinacol ester (3a) was unstable,[20] the crude prod-
uct was subjected to oxidation with NaBO3, followed by
treatment with (Boc)2O (Boc=tert-butoxycarbonyl). This
method afforded O-tert-butoxycarbonyl-8-hydroxyquinoline
(6a) in 68% yield after purification by silica-gel chromatog-
raphy. No other isomers were detected in the crude reaction
mixture. Thus, the site selectivity of the borylation reaction
was excellent. Based on the fact that the reaction of 2-sub-
stituted quinolines (see below) proceeded with exclusive se-
[c] Prof. Dr. T. B. Marder
Institut fꢁr Anorganische Chemie
Julius–Maximilians–Universitꢂt Wꢁrzburg
Am Hubland, 97074 Wꢁrzburg (Germany)
E-mail: todd.marder@uni-wuerzburg.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201301423.
Chem. Asian J. 2014, 9, 434 – 438
434
ꢃ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemasianj.org
Masaya Sawamura et al.
tance of sp3-hybridization of the P substituent. Homogene-
ous monodentate phosphane ligands such as Ph-SMAP,[24]
PMe3, PBu3, PCy3, PtBu3, PPh3, and XPhos (XPhos=2-dicy-
clohexylphosphino-2’,4’,6’-triisopropylbiphenyl) induced no
reaction or only trace reactions. No reaction occurred when
a phosphane-free Ir system was used. These ligand effects
indicate the crucial importance of both the SMAP structure
and its immobilization on a solid surface.
The method using the Silica–SMAP–Ir system was broad-
ly applicable to substituted quinolines. The results of boryla-
tion of monosubstituted quinolines are summarized in
Table 1. C2 substitution generally resulted in very clean
C(8)–H borylation reactions without reduced side products.
Scheme 1. C8 borylation of quinoline (1a) with pinB–Bpin (2) in the
presence of a Silica–SMAP–Ir catalyst.
Table 1. Silica–SMAP–Ir-catalyzed borylation of monosubstituted quino-
lines.[a]
Entry
Substrate
Product
T [8C]
Yield [%]
lectivity, we assumed that Ir-catalyzed addition of the pinB-
H (5) byproduct across the C=N bond (hydroboration) of
1a triggered reductive side reactions.[21] In fact, the reaction
of 1a with 5 (1.1 equiv) instead of 2, under otherwise identi-
cal conditions, produced the C8-borylated product 3a in
only 17% yield, while giving the reduced product 4a in an
increased yield of 30% with 67% conversion of 1a (analysis
1
50
80
86[b] (99)[c]
91[b] (99)[c]
2[d]
3
4
5
6
50
50
50
60
80[b] (99)[c]
74[b] (88)[c]
81[b] (99)[c]
61[e]
1
based on H NMR spectroscopy).
The selective borylation at the C8 position is thought to
be due to coordination of the ring nitrogen atom to the Ir
catalyst center.[22] This contrasts with previous directed (het-
À
ero)arene C H borylation using Silica-SMAP, which re-
quired pendant functional groups as coordination-based di-
recting moieties.[12c–e,g] The Ir center is most likely mono-P-
ligated and in a monomeric form because of the geometrical
constraint of the directional phosphane molecule (SMAP)
that is immobilized on the solid surface in a site-isolated
À
fashion. Thus, C H bond cleavage should occur through
a four-membered iridacyclic reaction pathway. Interestingly,
7
8
60
60
71[e]
the corresponding Rh catalyst (Silica-SMAP/[Rh
ACHTUNGTRENNUNG(cod)]2) did not yield the C8-borylated product (3a) with
60% consumption of 1a under otherwise identical condi-
tions, and instead gave a complex mixture containing the
tetrahydroquinoline 4a in 6% yield.
ACHTUNGTRNE(NUNG OMe)-
60[e]
[a] Conditions: 1 (0.30 mmol), 2 (0.33 mmol), [IrACHTNUTRGENNUG(OMe)HCATUNGTNER(NUGN cod)]2 (1 mol%),
The Ir-catalyzed borylation of 1a did not proceed effi-
ciently with the phosphane ligands shown in Figure 1. The
use of silica-supported triarylphosphane ligand (Silica-
TRIP),[12,23] a threefold-benzannulated analogue of Silica-
SMAP, gave only a trace of 3a, thereby showing the impor-
and Silica-SMAP (2 mol%) in MTBE (1.5 mL) for 12 h. [b] Yield of iso-
lated C8-borylated product 3. [c] Yield of 3, as determined by 1H NMR
spectroscopy of the crude product. [d] 1b (6 mmol), 2 (6.6 mmol), [Ir-
ACHUTNERGN(NUG OMe)CAHTUNGTERN(NUGN cod)]2 (0.025 mol%), and Silica-SMAP (0.05 mol%) in MTBE
(1.5 mL), at 808C for 12 h. [e] Yield of the isolated O-tert-butoxycarbon-
yl-8-hydroxyquinoline 6.
For example, 2-methylquinoline (1b, quinaldine) was con-
verted into 8-borylquinaldine (3b) in 99% yield (86% yield
after purification) without formation of a reduced heterocy-
clic compound (4) (Table 1, entry 1). In contrast, the reac-
tion of 1b with the Ir–dtbpy catalyst system gave the C4,
C6, and C7 borylation products in 16%, 27%, and 20%
yields, respectively, along with diborylation products.[16,17] It
was possible to reduce the catalyst loading of the Silica–
SMAP–Ir system to 0.05 mol% (Ir) upon scaling up this
Figure 1. Ligands that induced no reaction or trace reactions for the Ir-
catalyzed borylation of 1a.
Chem. Asian J. 2014, 9, 434 – 438
435
ꢃ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemasianj.org
Masaya Sawamura et al.
transformation (Table 1, entry 2). C8 borylation also pro-
ceeded cleanly, even with the sterically more demanding nPr
group (1c) at the C2 position (Table 1, entry 3). Further-
more, substitution with methoxy (1d) or N,N-diethylamino
(1e) groups at the terminus of the C2 pendant chain was tol-
erated (Table 1, entries 4 and 5). In contrast, monosubstitu-
tion with Me or MeO groups at the C3 (1 f), C4 (1g), and
C6 (1h) positions, leaving the C2 position unsubstituted, did
not cause a significant effect on the reaction profile of the
parent quinoline 1a (Table 1, entries 6–8).[25] These results
strongly support the above-mentioned assumption that the
C2 substituents blocked the undesired C=N reduction with
5.
with chlorine (Table 2, entries 1, 3, 6) or Boc-protected
oxygen atoms (Table 2, entry 4) was not detrimental to the
reaction. Importantly, the steric effects of substituents (Me,
MeO, Cl) at the adjacent C7 position did not hamper C8
borylation (Table 2, entries 6–8). To our knowledge, this is
À
the first demonstration of catalytic C H functionalization at
the C8 position of C7-substituted quinolines. The molecular
structure of 3n, in which there are no intra- or intermolecu-
À
lar B N interactions, was unambiguously determined by
single crystal X-ray diffraction analysis (see the Supporting
Information).
The reaction of 2,3-dimethylquinoxaline (1q) with
2.2 equivalents of 2, catalyzed by the Silica–SMAP–Ir
system, afforded the 5,8-diborylation-product 3q in 62%
yield, as shown in Equation (1). The quinoxaline heterocy-
clic scaffold is a versatile structural motif found in various
functional molecules with potential applications in the de-
velopment of electronic and luminescent devices.[26]
The results of C8 borylation of mono- or disubstituted
quinaldines (di- or trisubstituted quinolines) are summarized
in Table 2. Reflecting the substituent effect at the 2-position,
these substrates were converted cleanly into the correspond-
ing C8 borylation products in high yields. Ring substitution
Table 2. Silica–SMAP–Ir-catalyzed borylation of di- or trisubstituted qui-
nolines.[a]
Entry Substrate
Product
T [8C] Yield [%][b]
81
60
1
(94)
86
50
2
3
4
(99)
The C8-borylated quinaldine 3b can be used for various
transformations including oxidation,[27] one-carbon-homolo-
gation/oxidation sequence,[28] Rh-catalyzed Heck-type reac-
tion,[29] and Suzuki–Miyaura coupling[30] (Scheme 2). The ex-
cellent yields of these transformations show the utility of
C8-borylated quinoline derivatives as a point of structural
diversification.
79
60
(91)
50
76[c]
71
(86)
5
60
60
50
84
(96)
6[d]
86
(92)
7
84
(99)
8
50
Scheme 2. Transformations of the C8 borylation product 3b. Conditions:
[a] NaBO3·4H2O (3 equiv) in THF/H2O (1:1), rt, 3 h. [b] (Boc)2O
(2 equiv), 4-dimethylaminopyridine (DMAP, 0.1 equiv) in THF, rt, 1 h.
[c] Bromochloromethane (2 equiv), nBuLi in hexane (1.7m, 1.7 equiv) in
[a] The reaction was carried out with 1 (0.30 mmol), 2 (0.33 mmol), [Ir-
(OMe)(cod)]2 (1 mol%), and Silica–SMAP (2 mol%) in MTBE (1.5 mL)
G
ACHTUNGTRENNUNG
for 12 h. [b] Yields of the purified boronates (3). Yields of 3 based on
1H NMR analysis of crude products are shown in parentheses. [c] Yield
of isolated arylation product 9l. As the boronate 3l was unstable, it was
transformed into 9l through Suzuki–Miyaura coupling with methyl 4-bro-
mobenzoate under the conditions described in Scheme 2. [d] One equiva-
lent of 2 was employed.
THF, À788C to rt, 1 h. [d] nButyl acrylate (5 equiv), [Rh(OH)
ACHTUNGTRENNUNG(cod)]2
(2.5 mol%) in 1,4-dioxane/H2O (50:1), 908C, 16 h. [e] Methyl 4-bromo-
benzoate (1.5 equiv), [PdACTHNUTRGNEU(GN PPh3)4] (5 mol%), K3PO4 (3 equiv) in THF/
H2O (5:1), 608C, 12 h.
Chem. Asian J. 2014, 9, 434 – 438
436
ꢃ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemasianj.org
Masaya Sawamura et al.
a
magnetic stirring bar. A solution of [IrCAHTGUNTREN(UNGN OMe)CATHUNGRTEN(NUGN cod)]2 (2.0 mg,
To demonstrate further the utility of C8 borylation, we
synthesized a corticotropin-releasing factor1 (CRF1) receptor
0.003 mmol, 1 mol%) in MTBE (1 mL), and quinaldine (1b; 41.6 mg,
0.3 mmol) were added successively. The tube was sealed with a screw cap
and removed from the glove box. The reaction mixture was stirred at
508C for 12 h, and filtered through a glass pipette equipped with a cotton
plug. Solvent was removed under reduced pressure. An internal standard
(1,1,2,2-tetrachloroethane) was added to the residue to determine the
yield of the product 3b by 1H NMR spectroscopy (99%). The crude ma-
terial was purified by Kugelrohr distillation (1 mmHg, 1108C) to give 3b
(0.26 mmol, 67.6 mg, in 86% isolated yield).
À
antagonist (14) based on a late-stage C H borylation strat-
egy, as outlined in Scheme 3.[15a] Commercially available 3-
Acknowledgements
This work was supported by Grants-in-Aid for Scientific Research on In-
novative Areas “Reaction Integration” (MEXT and ACT-C, JST) to M.S.
and by a Grant-in-Aid for Young Scientists (JSPS) to K.S.
À
Keywords: borylation · C H activation · heterogeneous
catalysis · iridium · quinoline
Scheme 3. Synthesis of CRF1 receptor antagonist based on a late-stage
À
C H borylation strategy.
[1] Bioactive compounds, see: a) T. Eicher, S. Hauptmann, A. Speicher,
The Chemistry of Heterocycles, 2nd ed., Wiley-VCH, Weinheim,
2003; b) J. P. Michael, Nat. Prod. Rep. 2008, 25, 166–187.
[2] Dyes, see: C. H. McAteer, M. Balasubramanian, R. Murugan in
Comprehensive Heterocyclic Chemistry III, Vol. 7 (Eds.: A. R. Ka-
trizky, C. A. Ramsden, E. F. V. Scriven, R. J. K. Taylor), Elsevier,
Oxford, 2008, Chap. 7.06, pp. 309–336.
[3] OLEDs, see: a) J. Shinar, Organic Light-Emitting Devices: A Survey,
Springer, Berlin, 2003; b) V. Bulovic, M. A. Baldo, S. R. Forrest in
Organic Electronic Materials (Eds.: R. Farchioni, G. Grosso),
Springer, Berlin, 2001, pp. 391–439; c) C. H. Chen, J. Shi, Coord.
Chem. Rev. 1998, 171, 161–174.
[4] a) A. M. Berman, J. C. Lewis, R. G. Bergman, J. A. Ellman, J. Am.
Chem. Soc. 2008, 130, 14926–14927; b) J. Ryu, S. H. Cho, S. Chang,
Angew. Chem. 2012, 124, 3737–3741; Angew. Chem. Int. Ed. 2012,
51, 3677–3681.
[5] a) S. H. Cho, S. J. Hwang, S. Chang, J. Am. Chem. Soc. 2008, 130,
9254–9256; b) A. Larivꢄe, J. J. Mousseau, A. B. Charette, J. Am.
Chem. Soc. 2008, 130, 52–54; c) L.-C. Campeau, D. R. Stuart, J.-P.
Leclerc, M. Bertrand-Laperle, E. Villemure, H.-Y. Sun, S. Lasserre,
N. Guimond, M. Lecavallier, K. Fagnou, J. Am. Chem. Soc. 2009,
131, 3291–3306; d) B. Xiao, Z.-J. Liu, L. Liu, Y. Fu, J. Am. Chem.
Soc. 2013, 135, 616–619.
[6] a) M. Tobisu, I. Hyodo, N. Chatani, J. Am. Chem. Soc. 2009, 131,
12070–12071; b) I. Hyodo, M. Tobisu, N. Chatani, Chem. Asian J.
2012, 7, 1357–1365.
[7] D. Zhao, W. Wang, F. Yang, J. Lan, L. Yang, G. Gao, J. You, Angew.
Chem. 2009, 121, 3346–3350; Angew. Chem. Int. Ed. 2009, 48, 3296–
3300.
[8] I. B. Seiple, S. Su, R. A. Rodriguez, R. Gianatassio, Y. Fujiwara,
A. L. Sobel, P. S. Baran, J. Am. Chem. Soc. 2010, 132, 13194–13196.
[9] J. Kwak, M. Kim, S. Chang, J. Am. Chem. Soc. 2011, 133, 3780–
3783.
[10] Knochel and co-workers reported regioselective magnesiation at the
C8 position of 2-bromo-3-pivaloyl-4-ethoxycarbonylquinoline: N.
Boudet, J. R. Lachs, P. Knochel, Org. Lett. 2007, 9, 5525–5528.
methoxyaniline (10) was transformed into 4-chloro-7-me-
thoxyquinaldine (11) according to the literature.[31] Treat-
ment of 11 with excess dipropylamine in the presence of
TsOH furnished 4-dipropylamino-7-methoxyquinalidine (12)
À
as a substrate for Ir-catalyzed C H borylation. The reaction
of 12 with one equivalent of diboron reagent 2 in the pres-
ence of the Silica–SMAP–Ir catalyst system (2 mol%) at
608C over 12 h cleanly produced the desired C8-borylation
product 13 (unpurified) with good site selectivity. Remarka-
À
bly, the C H bonds at the C3 and C5 positions, which are
proximal to the dipropylamino group, were intact. Finally,
Suzuki–Miyaura coupling between the boronate 13 and 4-
bromochlorobenzene gave the CRF1 receptor antagonist 14
(57% yield from 12). The highly functionalized boronate 13
has the potential to be a versatile precursor for analogous 8-
substituted quinoline derivatives.
In summary, a heterogeneous Ir catalyst system based on
the silica-supported cage-type monophosphane ligand Silica-
À
SMAP enabled catalytic site-selective C H borylation of
quinolines at the C8 position, thereby complementing exist-
ing quinoline borylation methods using Ir–bipyridine-type
catalysts. The synthesis of a CRF1 receptor antagonist based
À
on a late-stage C H borylation strategy demonstrated the
utility of the C8 borylation. Exploration of the applicability
of this strategy for efficient synthesis of complex heterocy-
clic compounds and for the development of new functional
molecules is underway.
À
[11] C3- and C4-selective C H arylation reactions of pyridines with
amide directing groups: a) M. Wasa, B. T. Worrell, J.-Q. Yu, Angew.
Chem. 2010, 122, 1297–1299; Angew. Chem. Int. Ed. 2010, 49, 1275–
1277; b) M. Ye, G.-L. Gao, A. J. F. Edmunds, P. A. Worthington,
J. A. Morris, J.-Q. Yu, J. Am. Chem. Soc. 2011, 133, 19090–19093.
[12] Silica-SMAP and Silica-TRIP can be purchased from Wako Pure
Chemical Industries, Ltd., Osaka, Japan. For the synthesis and appli-
cations of Silica-SMAP, see: a) G. Hamasaka, A. Ochida, K. Hara,
Experimental Section
Typical Procedure for the Borylation of Quinoline Derivatives
In
a , 85.7 mg, 0.006 mmol,
glove box, Silica-SMAP (0.070 mmolgÀ1
2 mol%), bis(pinacolato)diboron (2; 83.8 mg, 0.33 mmol), and anhydrous,
degassed MTBE (0.5 mL) were placed in a 10 mL glass tube containing
Chem. Asian J. 2014, 9, 434 – 438
437
ꢃ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemasianj.org
Masaya Sawamura et al.
M. Sawamura, Angew. Chem. 2007, 119, 5477–5479; Angew. Chem.
Int. Ed. 2007, 46, 5381–5383; b) G. Hamasaka, S. Kawamorita, A.
Ochida, R. Akiyama, K. Hara, A. Fukuoka, K. Asakura, W. J. Chun,
H. Ohmiya, M. Sawamura, Organometallics 2008, 27, 6495–6506;
c) S. Kawamorita, H. Ohmiya, K. Hara, A. Fukuoka, M. Sawamura,
J. Am. Chem. Soc. 2009, 131, 5058–5059; d) S. Kawamorita, H.
Ohmiya, M. Sawamura, J. Org. Chem. 2010, 75, 3855–3858; e) K.
Yamazaki, S. Kawamorita, H. Ohmiya, M. Sawamura, Org. Lett.
2010, 12, 3978–3981; f) S. Kawamorita, H. Ohmiya, T. Iwai, M. Sa-
wamura, Angew. Chem. 2011, 123, 8513–8516; Angew. Chem. Int.
Ed. 2011, 50, 8363–8366; g) S. Kawamorita, T. Miyazaki, H.
Ohmiya, T. Iwai, M. Sawamura, J. Am. Chem. Soc. 2011, 133,
19310–19313; h) S. Kawamorita, R. Murakami, T. Iwai, M. Sawa-
mura, J. Am. Chem. Soc. 2013, 135, 2947–2950.
[19] 1,2-Dihydroquinoline was not detected in the crude product. No
trace of 2-borylation was observed.
[20] For hydrolysis and dimerization of quinoline-8-boronic acid pinaco-
lates, see: a) J.-H. Son, M. A. Pudenz, J. D. Hoefelmeyer, Dalton
Trans. 2010, 39, 11081–11090; b) Y. Zhang, M. Li, S. Chandrasekar-
an, X. Gao, X. Fang, H.-W. Lee, K. Hardcastle, J. Yang, B. Wang,
Tetrahedron 2007, 63, 3287–3292. See also ref. 18.
[21] Hydroboration of pyridines with pinB-H (5) catalyzed by Mg or Rh
systems: a) M. Arrowsmith, M. S. Hill, T. Hadlington, G. Kociok-
Kçhn, C. Weetman, Organometallics 2011, 30, 5556–5559; b) K.
Oshima, T. Ohmura, M. Suginome, J. Am. Chem. Soc. 2012, 134,
3699–3702. For an uncatalyzed multiple hydroboration of 2-ethynyl-
pyridine, see: c) C. D. Entwistle, A. S. Batsanov, J. A. K. Howard,
M. A. Fox, T. B. Marder, Chem. Commun. 2004, 702–703.
[22] The importance of N–Ir coordination for catalysis by the Silica-
SMAP-Ir system is indicated by the fact that C8 substitution severe-
ly inhibited the reaction of quinoline derivatives with the diboron 2.
For instance, the reaction of 8-methylquinoline (Silica–SMAP–Ir,
2 mol%; octane, 1208C, 14 h) afforded 3-borylation and 4-borylation
products in 13% and 2% yields, respectively; a reduction product
was not produced either. Almost no reaction was observed with 8-
chloro-2-methylquinoline (Silica–SMAP–Ir, 2 mol%; hexane, 508C,
15 h).
À
[13] For the Ir-catalyzed C H borylation of indoles at the C7 position,
see: a) S. Paul, G. A. Chotana, D. Holmes, R. C. Reichle, R. E. Mal-
eczka, Jr., M. R. Smith, III, J. Am. Chem. Soc. 2006, 128, 15552–
15553; b) D. W. Robbins, T. A. Boebel, J. F. Hartwig, J. Am. Chem.
Soc. 2010, 132, 4068–4069.
À
[14] For the Ir-catalyzed C H borylation of arenes based on the direct-
ing effect of a nitrogen ring atom of pendant heteroarenes, see:
a) A. Ros, B. Estepa, R. Lꢅpez-Rodrꢆguez, E. ꢇlvarez, R. Fernꢈn-
dez, J. M. Lassaletta, Angew. Chem. 2011, 123, 11928–11932;
Angew. Chem. Int. Ed. 2011, 50, 11724–11728; b) A. Ros, R. Lꢅpez-
Rodrꢆguez, B. Estepa, E. ꢇlvarez, R. Fernꢈndez, J. M. Lassaletta, J.
Am. Chem. Soc. 2012, 134, 4573–4576. For the Rh-catalyzed reac-
tion, see Ref. [12g]. For the Ir catalysis with sp3-N-directing groups,
see: c) A. J. Roering, L. V. A. Hale, P. A. Squier, M. A. Ringgold,
E. R. Wiederspan, T. B. Clark, Org. Lett. 2012, 14, 3558–3561.
[15] a) C. Q. Huang, K. Wilcoxen, J. R. McCarthy, M. Haddach, T. R.
Webb, J. Gu, Y.-F. Xie, D. E. Grigoriadis, C. Chen, Bioorg. Med.
Chem. Lett. 2003, 13, 3375–3379; b) Y. Ye, Q. Liao, J. Wei, Q. Gao,
Neurochem. Int. 2010, 56, 107–117.
[23] S. Kawamorita, T. Miyazaki, T. Iwai, H. Ohmiya, M. Sawamura, J.
Am. Chem. Soc. 2012, 134, 12924–12927.
[24] The synthesis, properties, and use of non-immobilized SMAP deriva-
tives (silicon-constrained monodentate trialkylphosphane): a) A.
Ochida, K. Hara, H. Ito, M. Sawamura, Org. Lett. 2003, 5, 2671–
2674; b) A. Ochida, S. Ito, T. Miyahara, H. Ito, M. Sawamura,
Chem. Lett. 2006, 35, 294–295; c) A. Ochida, G. Hamasaka, Y. Ya-
mauchi, S. Kawamorita, N. Oshima, K. Hara, H. Ohmiya, M. Sawa-
mura, Organometallics 2008, 27, 5494–5503.
[25] Because of the instability of 3, the borylation products (3 f–h) were
converted into the corresponding O-tert-butoxycarbonyl-8-hydroxy-
quinoline 6 through the oxidation/Boc-protection protocol.
[26] Selected examples of applications of quinoxalines: a) J. L. Sessler,
H. Maeda, T. Mizuno, V. M. Lynch, H. Furuta, J. Am. Chem. Soc.
2002, 124, 13474–13479; b) M. R. Myers, W. He, B. Hanney, N.
Setzer, M. P. Maguire, A. Zulli, G. Bilder, H. Galzcinski, D. Amin,
S. Needle, A. P. Spada, Bioorg. Med. Chem. Lett. 2003, 13, 3091–
3095; c) Y. B. Kim, Y. H. Kim, J. Y. Park, S. K. Kim, Bioorg. Med.
Chem. Lett. 2004, 14, 541–544; d) Y. Akai, T. Yamamoto, Y. Nagata,
T. Ohmura, M. Suginome, J. Am. Chem. Soc. 2012, 134, 11092–
11095; e) S. Li, A. Li, J. Yu, A. Zhong, S. Chen, R. Tang, X. Deng, J.
Qin, Q. Li, Z. Li, Macromol. Rapid Commun. 2013, 34, 227–233.
[27] C. N. Farthing, S. P. Marsden, Tetrahedron Lett. 2000, 41, 4235–4238.
[28] a) H. C. Brown, S. M. Singh, M. V. Rangaishevi, J. Org. Chem. 1986,
51, 3150–3155; b) D. S. Matteson, Chem. Rev. 1989, 89, 1535–1551.
[29] M. Lautens, A. Roy, K. Fukuoka, K. Fagnou, B. Martꢆn-Matute, J.
Am. Chem. Soc. 2001, 123, 5358–5359.
[16] J. Takagi, K. Sato, J. F. Hartwig, T. Ishiyama, N. Miyaura, Tetrahe-
dron Lett. 2002, 43, 5649–5651.
[17] a) S. Shimada, A. S. Batsanov, J. A. K. Howard, T. B. Marder,
Angew. Chem. 2001, 113, 2226–2229; Angew. Chem. Int. Ed. 2001,
40, 2168–2171; b) W. H. Lam, K. C. Lam, Z. Lin, S. Shimada, R. N.
Perutz, T. B. Marder, Dalton Trans. 2004, 1556–1562; c) D. N. Cov-
entry, A. S. Batsanov, A. E. Goeta, J. A. K. Howard, T. B. Marder,
R. N. Perutz, Chem. Commun. 2005, 2172–2174; d) I. A. I. Mkhalid,
D. N. Coventry, D. Albesa-Jove, A. S. Batsanov, J. A. K. Howard,
R. N. Perutz, T. B. Marder, Angew. Chem. 2006, 118, 503–505;
Angew. Chem. Int. Ed. 2006, 45, 489–491; e) P. Harrisson, J. Morris,
T. B. Marder, P. G. Steel, Org. Lett. 2009, 11, 3586–3589; f) I. A. I.
Mkhalid, J. H. Barnard, T. B. Marder, J. M. Murphy, J. F. Hartwig,
Chem. Rev. 2010, 110, 890–931; g) T. E. Hurst, T. K. Macklin, M.
Becker, E. Hartmann, W. Kꢁgel, J.-C. Parisienne-La Salle, A. S. Bat-
sanov, T. B. Marder, V. Snieckus, Chem. Eur. J. 2010, 16, 8155–8161;
h) A. G. Crawford, Z. Liu, I. A. I. Mkhalid, M.-H. Thibault, N.
Schwarz, G. Alcaraz, A. Steffen, J. C. Collings, A. S. Batsanov,
J. A. K. Howard, T. B. Marder, Chem. Eur. J. 2012, 18, 5022–5035;
i) Z. Liu, Y. Wang, Y. Chen, J. Liu, Q. Fang, C. Kleeberg, T. B.
Marder, J. Org. Chem. 2012, 77, 7124–7128; j) H. Tajuddin, P. Har-
risson, B. Bitterlich, J. C. Collings, N. Sim, A. S. Batsanov, M. S.
Cheung, S. Kawamorita, A. C. Maxwell, L. Shukla, J. Morris, Z. Lin,
T. B. Marder, P. G. Steel, Chem. Sci. 2012, 3, 3505–3515.
[30] A. Suzuki, Angew. Chem. 2011, 123, 6854–6869; Angew. Chem. Int.
Ed. 2011, 50, 6722–6737.
[31] Y. Abe, H. Kayakiri, S. Satoh, T. Inoue, Y. Sawada, N. Inamura, M.
Asano, I. Aramori, C. Hatori, H. Sawai, T. Oku, H. Tanaka, J. Med.
Chem. 1998, 41, 4062–4079.
Received: October 23, 2013
Published online: December 4, 2013
[18] Y. Zhang, J. Gao, W. Li, H. Lee, B. Z. Lu, C. H. Senanayaka, J. Org.
Chem. 2011, 76, 6394–6400.
Chem. Asian J. 2014, 9, 434 – 438
438
ꢃ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim