Directed ortho borylation of phenol derivatives catalyzed by a silica-supported iridium complex

Article abstract of DOI:10.1021/ol101493m

The directed ortho borylation of phenol derivatives protected with an N,N-diethylcarbamoyl group was efficiently catalyzed by an immobilized monophosphine-Ir system, which was prepared in situ from [Ir(OMe)(cod)] ₂ and a silica-supported, compact phosphine. The utility of the carbamoyloxy group as a leaving group for metal-catalyzed cross-coupling reactions was demonstrated by its utilization in the synthesis of a terphenyl derivative.

Full text of DOI:10.1021/ol101493m

ORGANIC
LETTERS
2010
Vol. 12, No. 18
3978-3981
Directed Ortho Borylation of Phenol
Derivatives Catalyzed by a Silica-
Supported Iridium Complex
Kenji Yamazaki, Soichiro Kawamorita, Hirohisa Ohmiya, and Masaya Sawamura*
Department of Chemistry, Faculty of Science, Hokkaido UniVersity,
Sapporo 060-0810, Japan
sawamura@sci.hokudai.ac.jp
Received June 29, 2010
ABSTRACT
The directed ortho borylation of phenol derivatives protected with an N,N-diethylcarbamoyl group was efficiently catalyzed by an immobilized
monophosphine-Ir system, which was prepared in situ from [Ir(OMe)(cod)]2 and a silica-supported, compact phosphine. The utility of the
carbamoyloxy group as a leaving group for metal-catalyzed cross-coupling reactions was demonstrated by its utilization in the synthesis of
a terphenyl derivative.
Phenol derivatives are fundamental structural components
of natural products, pharmaceuticals, ligands for transition-
metal complexes, and advanced materials. On the other hand,
they are widely used in organic synthesis as an electrophilic
cross-coupling partner.1 Therefore, the development of a new
method to functionalize phenol derivatives is highly desir-
able.
We previously reported that the directed ortho borylation
of functionalized arenes with bis(pinacolato)diboron (pinB-
Bpin) was efficiently and selectively catalyzed by an im-
mobilized monophosphine-Ir system [Silica-SMAP-Ir (1)],
which was prepared in situ from a silica-supported, compact
monophosphine (Silica-SMAP) and [Ir(OMe)(cod)]2.2-7 To
expand the synthetic utility of the method, we examined the
ortho-C-H borylation of phenol derivatives.8 However, our
screening of phenol derivatives revealed that the use of
(2) (a) Kawamorita, S.; Ohmiya, H.; Hara, K.; Fukuoka, A.; Sawamura,
M. J. Am. Chem. Soc. 2009, 131, 5058–5059. (b) Kawamorita, S.; Ohmiya,
H.; Sawamura, M. J. Org. Chem. 2010, 75, 3855–3858.
(3) SMAP (silicon-constrained monodentate trialkylphosphine): (a)
Ochida, A.; Hara, K.; Ito, H.; Sawamura, M. Org. Lett. 2003, 5, 2671–
2674. (b) Ochida, A.; Ito, S.; Miyahara, T.; Ito, H.; Sawamura, M. Chem.
Lett. 2006, 35, 294–295. (c) Ochida, A.; Hamasaka, G.; Yamauchi, Y.;
Kawamorita, S.; Oshima, N.; Hara, K.; Ohmiya, H.; Sawamura, M.
Organometallics 2008, 27, 5494–5503.
(4) For the synthesis and applications of silica-SMAP, see: (a) Hamasaka,
G.; Ochida, A.; Hara, K.; Sawamura, M. Angew. Chem., Int. Ed. 2007, 46,
5381–5383. (b) Hamasaka, G.; Kawamorita, S.; Ochida, A.; Akiyama, R.;
Hara, K.; Fukuoka, A.; Asakura, K.; Chun, W. J.; Ohmiya, H.; Sawamura,
M. Organometallics 2008, 27, 6495–6506. (c) Kawamorita, S.; Hamasaka,
G.; Ohmiya, H.; Hara, K.; Fukuoka, A.; Sawamura, M. Org. Lett. 2008,
10, 4697–4700.
(1) For nickel-catalyzed Suzuki-Miyaura cross-couplings of pheol
derivatives, see: (a) Quasdorf, K. W.; Riener, M.; Petrova, K. V.; Garg,
N. K. J. Am. Chem. Soc. 2009, 131, 17748–17749. (b) Antoft-Finch, A.;
Blackburn, T.; Snieckus, V. J. Am. Chem. Soc. 2009, 131, 17750–17752.
(c) Xu, L.; Li, B.-J.; Wu, Z.-H.; Lu, X.-Y.; Guan, B.-T.; Wang, B.-Q.;
Zhao, K.-Q.; Shi, Z.-J. Org. Lett. 2010, 12, 884–887. See also: (d) Knappke,
C. E. I.; Jacobi von Wangelin, A. J. Angew. Chem., Int. Ed. 2010, 49, 3568–
3570.
(5) For a review on the C-H borylaion of arenes, see: Mkhalid, I. A.;
Barnard, J. H.; Marder, T. B.; Murphy, J. M.; Hartwig, J. F. Chem. ReV.
2010, 110, 890–931.
(6) For the directed ortho borylation of benzoate derivatives catalyzed
by the Ir-P[3,5-(CF3)2C6H3]3 system, see: Ishiyama, T.; Isou, H.; Kikuchi,
T.; Miyaura, N. Chem. Commun. 2010, 46, 159–161.
(7) For ortho borylation of arenes directed by a Me2HSi group, see:
Boebel, T. A.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130, 7534–7535.
10.1021/ol101493m  2010 American Chemical Society
Published on Web 08/23/2010

common phenol protecting groups such as acetyl, meth-
oxycarbonyl and tert-butoxycarbonyl groups were not
effective for the ortho borylation (vide infra). In further
investigations, we have found that an N,N-diethyl-
O-carbamoyl protecting group can efficiently deliver the
boryl group to the ortho-position of phenol derivatives.
The utility of N,N-diethylcarbamoyl phenol derivatives as
an electrophilic cross-coupling partner is an attractive
feature of this transformation.1
Table 1. Borylation of Phenol Derivatives with Different
O-Protecting Groupsa
The reaction of O-phenyl carbamate 3aa (1 mmol) and
pinacolatoborane (H-BPin) 2 (0.5 mmol) in the presence of
0.5 mol % of Silica-SMAP-Ir(OMe)(cod) (1) in hexane at
70 °C for 12 h gave the ortho borylation product 4aa in 64%
isolated yield (based on 2, 74% NMR yield), together with
a small amount of bis-ortho-borylation product 4a′a (3%)
(Scheme 1).9,10 The reaction was completely regioselective,
Scheme 1
a Conditions: 2 (0.5 mmol), 3 (1.0 mmol), Silica-SMAP-Ir(OMe)(cod)
(1, 0.5 mol %), octane (1.0 mL), 100 °C, 24 h. b 1H NMR yield of 4 based
on 2. c Total yield of isomeric arylboronates.
(3ad) showed only a little directing effect toward the ortho
borylation [o/(m + p) 65:35] (entry 3). The reaction stopped
at a low conversion of the 3ad, giving a very low yield of
the arylboronates together with a larger amount of phenol
(16% based on 3ad).
Although the methoxycarbonyloxy group induced the ortho
borylation with complete selectivity, the conversion stayed
very low (Table 1, entry 4). An increase in the steric demand
of the carbonate group by changing the Me group to the tBu
group resulted in an increase in the conversion, but the yield
of the ortho borylation product was low (33%, entry 5).
Phenyl N,N,N′,N′-tetramethylphosphoryldiamide (3ag) and
phenyl methanesulfonate (3ah) also underwent the regiose-
lective ortho borylation (entries 6 and 7), but the conversion
and the yield of the boronates were not improved as
compared with those in the reaction of the carbonates (3ae
and 3af). Our attempt to improve the yields of 4ae-4ah by
applying longer reaction time was in vain, indicating that
catalyst inactivation was significant. Accordingly, functional
groups such as carbonates, phosphorodiamide, and sulfonate
seem to be labile under the catalytic conditions.
delivering the boryl group to the ortho-position. When
bis(pinacolato)diboron (pinB-Bpin) was employed instead of
H-Bpin, the reaction afforded 4aa in 113% NMR yield based
on pinB-Bpin (70 °C, 8 h, 56% based on B atom): H-Bpin
reacted with 3aa to some extent. Although the reactivity of
pinB-Bpin is higher than that of H-Bpin, we mostly used
H-Bpin as a boron source for further study in consideration
of atom economy.
Table 1 shows that most of the common protecting groups
other than the N,N-dialkylcarbamoyl group were not effective
for the ortho borylation of phenol derivatives in terms of
the directing power or product yields (0.5 mol % of Silica-
SMAP-Ir/2/octane/100 °C/24 h). The reactions of anisole
(3ab) and MOM-protected phenol (3ac) were not regiose-
lective (entries 1 and 2). An acetoxy group in acetylphenol
The Silica-SMAP-Ir catalyst (0.5 mol %) was applicable
to the reaction of various aryl carbamate derivatives with
one or two additional substituents on the aromatic ring. The
results are summarized in Table 2.9 Although, in most cases,
isolated yields of the arylboronates (4) were significantly
(8) For palladium-catalyzed ortho-C-H arylations of phenol derivatives,
see: (a) Xiao, B.; Fu, Y.; Xu, J.; Gong, T.-J.; Dai, J.-J.; Yi, J.; Liu, L.
J. Am. Chem. Soc. 2010, 132, 468–469. (b) Zhao, X.; Yeung, C. S.; Dong,
V. M. J. Am. Chem. Soc. 2010, 132, 5837–5844.
1
reduced as compared with the H NMR yields because of
(9) For Scheme 1 and Table 2, unreacted H-Bpin (2) was observed in
the crude materials (except for Table 2, entries 14, 15, and 18).
(10) The corresponding homogeneous catalysts that were prepared in
situ from [Ir(OMe)(cod)]2 and Ph-SMAP (0.5 mol % of Ir, Ir/P 1:1 or 1:2)
afforded no borylation compound under otherwise the same reaction
conditions, indicating that the phosphine immobilization is crucial. No
reaction occured in the absence of a phosphine ligand with any combinations
of [IrX(cod)]2 (X ) OMe, Cl; 0.5 mol % of Ir) and H-Bpin/pinB-Bpin.
the material loss during distillation or GPC purification, in
practice, the crude arylboronates would be usable for further
transformation.
The borylation of isomeric cresol derivatives 3b,c,h
occurred with high selectivity at the ortho-position of the
Org. Lett., Vol. 12, No. 18, 2010
3979

2, entry 13). Thus, the directing power of the carbamoyl
group is estimated to be comparable with that of the
methoxycarbonyl group.2a,b As shown in entry 14, the ester
one carbon distal to the aromatic ring did not direct the ortho
borylation. It should be noted that the borylation of the 2-
phenylacetate derivative 3o was successful even in the
presence of substantially acidic C-H protons, which are
activated by the ester and the aryl groups. As shown in entries
15 and 16, functional groups such as dialkyl carbonates and
cyclic acetals were compatible with the ortho borylaton of
the phenol derivatives.
Table 2. Borylation of Phenol Derivatives Catalyzed by the
Silica-SMAP-Ir Systema
More substituted phenol derivatives such as 2-methyl-5-
fluorophenol (3r) and 3,5-dimethylphenol (3s) derivatives
were borylated at the sterically hindered position to afford
the corresponding arylboronates 4r and 4s, respectively,
which are difficult to prepare by other methods (Table 2,
entries 17 and 18).
Transformations of the borylated aryl O-carbamate 4aa
were conducted in two ways to demonstrate its utility
(Scheme 2). Suzuki-Miyaura coupling between 4aa and
Scheme 2. Transformations with Borylated Phenol Derivatives
a Conditions: 2 (0.5 mmol), 3 (entries 1-6, 12, and 14-16, 0.6 mmol;
entries 7-11, 13, 17, and 18, 1.0 mmol), Silica-SMAP-Ir(OMe)(cod) (1,
0.5 mol %), hexane, 70 °C, 12-24 h. b Isolated yield of 4 based on 2. The
yield in parentheses was determined by 1H NMR. c A mixture of meta-
and para-isomers was detected in the crude mixture (entry 2, 4%; entry 4,
5%; entry 6, 3%). d Silica-SMAP-Ir(OMe)(cod) (1) (1.0 mol %) was used.
e Bis-ortho borylation product was detected in the crude mixture (entry 7,
6%; entry 8, 5%; entry 9, 6%; entry 10, 5%; entry 11, 7%; entry 13, 2%).
f Total yield of isomeric arylboronates. g Bis(pinacolato)diboron (pinB-Bpin,
0.5 mmol) was used instead of H-Bpin (2). Yield of 4 based on pinB-Bpin.
h The reaction carried out in octane at 120 °C for 24 h.
2-bromothiophene followed by the reductive removal of the
carbamate group afforded the thiophene-substituted phenol
derivative 6. On the other hand, we also tried to use the
carbamate moiety as a leaving group for metal-catalyzed
cross-coupling reactions. Initially, the substituted biphenyl
7, which was obtained by the cross-coupling between the
boronate 4aa and bromobenzene, was subjected to the Ni-
catalyzed aryl-aryl cross-coupling with 4-methoxyphenyl-
boronic acid under the conditions described by Snieckus and
Garg,1 but unfortunately, the reaction resulted in a poor yield.
Next we tried the coupling reaction with the corresponding
Grignard reagent under Nakamura’s conditions [Ni(acac)2
and a hydroxyphosphine ligand].11 The Ni-catalyzed reaction
proceeded at room temperature to furnish the terphenyl
derivative 8. The three-component coupling represents the
utility of the directed ortho borylation of the phenol deriva-
tives in the preparation of multiaromatic compounds.
In summary, the directed ortho borylation of phenol
derivatives protected with an N,N-diethylcarbamoyl group
wasefficientlycatalyzedbyanimmobilizedmonophosphine-Ir
carbamate moiety (Table 2, entries 1, 2, and 7), although
the reaction of o-cresol 3b afforded 4b in a lower yield. The
ring substitution with MeO, CF3, Ph, or Cl groups was
tolerated at the meta- and para-positions (entries 3-6 and
8-11). The regioselectivity with the Cl-substituted aryl
carbamate (3g,l) indicates that the carbamoyloxy group is a
stronger directing group than the Cl atom (entries 6 and 11).
Bromophenol derivative 3m also underwent the selective
ortho borylation to form 4m with a moderate yield (70%
NMR yield), leaving the Br atom untouched (entry 12).
The borylation with p-hydroxybenzoate derivative 3n
occurred at the ortho-positions of either the carbamoyl group
or the ester group in a 61:39 regioselectivity (4n/4n′, Table
(11) Yoshikai, N.; Matsuda, H.; Nakamura, E. J. Am. Chem. Soc. 2009,
131, 9590–9599.
3980
Org. Lett., Vol. 12, No. 18, 2010

system (Silica-SMAP-Ir). The carbamoyloxy group not only
works as a directing group for the ortho borylation but also
is usable as a leaving group in the cross-coupling reactions
as demonstrated in the synthesis of a terphenyl derivative.
Synthesis Based on Reaction Integration) (MEXT). S.K.
thanks JSPS for scholarship.
Supporting Information Available: Experimental pro-
cedures and NMR spectra for new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
Acknowledgment. This work was supported by Grants-
in-Aid for Scientific Research on Priority Area (Chemistry
of Concerto Catalysis) and on Innovative Area (Organic
OL101493M
Org. Lett., Vol. 12, No. 18, 2010
3981