Regioselective remote functionalization of biaryl framework via tethered ortho-quinol intermediate

Article abstract of DOI:10.1002/asia.201000533

An umpoled method for regioselective functionalization of biaryls is demonstrated. As a model substrate, binol was converted into a tethered ortho-quinol derivative, allowing selective installation of nucleophiles at the C4 or C3 position to give monofunctionalized binol derivatives with complete retention of the axial stereochemistry. Copyright

Full text of DOI:10.1002/asia.201000533

DOI: 10.1002/asia.201000533
Regioselective Remote Functionalization of Biaryl Framework via Tethered
ortho-Quinol Intermediate
Yasuhito Koyama, Hiroko Kataoka, Keisuke Suzuki,* and Takashi Matsumoto*[a]
Dedicated to Professor Eiichi Nakamura on the occasion of his 60th birthday
In connection with the synthesis of natural products with
densely functionalized biaryl structures such as 1[1a] and 2[1b]
(Figure 1), we found ourseleves in need of a viable means of
Scheme 1. Oxidative conversion of phenol into ortho-quinol.
ed cationic species II, and also because it is extremely reac-
tive, often undergoing spontaneous dimerization.[9,10] Even if
III is successfully available, the presence of multiple electro-
philic centers renders regiocontrolled reactions a challenge.
Recognizing these issues, we nonetheless became in-
trigued by the use of the ortho-quinol derivative based on
the following idea (Scheme 2); if a suitable oxygen nucleo-
Figure 1. Densely functionalized biaryl natural products.
selective elaboration of biaryl scaffolds with control of axial
stereochemistry.[2,3] For this purpose, we became intrigued by
the potential usefulness of ortho-quinol derivative III
(Scheme 1).[4,5] These could be generated by two-electron
oxidation of phenol I,[4,6,7] and corresponds to the polarity-
Scheme 2. Phenolic biaryl functionalization via a bridged ortho-quinol-
type intermediate. HO(drawn in red)=oxygen function.
inverted[8] (electrophilic) species of I. Species III, however,
has not been extensively employed in organic synthesis be-
cause its synthesis requires the selective trapping of extend-
phile were appended on the neighboring ring, then selective
trapping of the arenoxenium ion would be possible, allowing
access to masked ortho-quinol derivative V, amenable for
various elaborations.[11] In that case, two questions would
arise: 1) Can the position of the nucleophilic attack to V
with multiple electrophilic centers be controlled? and
2) Can the axial stereochemistry be maintained during these
processes?
[a] Prof. Dr. Y. Koyama,++ H. Kataoka, Prof. Dr. K. Suzuki,
Prof. Dr. T. Matsumoto+
Department of Chemistry
Tokyo Institute of Technology
SORST-JST Agency
2-12-1 Ookayama, Meguro-ku, Tokyo 152-8551 (Japan)
Fax : (+81)42-676-3257
E-mail: tmatsumo@toyaku.ac.jp
[+] Present Address:
School of Pharmacy
Tokyo University of Pharmacy and Life Sciences
++] Present Address:
Herein, we describe affirmative answers to these ques-
tions, as demonstrated by the selective elaboration of chiral,
nonracemic binol.[12] Table 1 features the conversion of (R)-
binol (3, 99% ee) into ortho-quinol derivative 5. Treatment
of 3 with Boc2O (pyridine, CH2Cl2, RT, 2.5 h) gave mono-
Boc-binol 4, possessing a Boc group that would be hopefully
served for the controlled oxidation to form the tethered
ortho-quinol carbonate 5.[13] However, the initial attempts
[
Department of Organic and Polymeric Materials
Tokyo Institute of Technology
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201000533.
Chem. Asian J. 2011, 6, 355 – 358
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355

COMMUNICATION
Table 1. Synthesis of ortho-quinol carbonate 5.
While the classical cuprate (MeLi, CuI) only effected reduc-
tion of 5 back to binol (3), Me3ZnLi[17] worked well to intro-
duce a methyl group at the C4 position. The reaction afford-
ed 4-methyl-1,1’-bi-2-naphthol (6, Figure 3) as a single
isomer via regioselective attack at the C4 position followed
by aromatization, decarboxylation of the adduct A, and pro-
tonation during workup. Importantly, the ee value was pre-
served (99% ee).
Entry
Oxidant
Solvent
Yield of 5 [%][a]
ee [%][b]
[c]
[d]
1
2
3
4
5
Pb
G
THF
THF
THF
CH3CN
–
–
33
86
84
–
–
–
99
99
[e]
PhI
PhI
PhI
PhI
ACHTUGNERTN(NUNG CF3)2CHOH
[a] Yield of isolated product. [b] Assessed by chiral HPLC (see the Ex-
perimental Section). [c] Performed in the absence of molecular sieves
4 ꢁ. [d] Intractable complex mixture. [e] See reference [15]. Boc=tert-
butoxycarbonyl.
Figure 3. NOESY correlation of 6.
were unfruitful; Pb
mixture (Table 1, entry 1),[9] while no reaction occurred with
PhI
(OAc)2 (entry 2).[14,15] After considerable experimenta-
tion, we found that ortho-quinol carbonate 5 was nicely ob-
tained by treatment of 4 with PhI(OCOCF3)2 in the pres-
ence of molecular sieves 4 ꢁ in MeCN or (CF3)2CHOH
(Table 1, entries 4, 5).[14] The ortho-quinol carbonate 5,
albeit labile to silica-gel chromatography, was isolated as a
stable solid. Recrystallization (hexane/acetone) gave beauti-
ful prisms suitable to X-ray crystallography, clearly showing
the twisted structure (Figure 2).[16] Notably, no decrease in
the ee value was observed, as evidenced by chiral HPLC
analysis (99% ee).
ACHTUNGTRENNUNG(OAc)4 only gave an intractable complex
G
Scheme 4 illustrates installation of an allyl group under
acid-catalyzed conditions. In the presence of a catalytic
amount of HNTf2, allyltrimethylsilane underwent a smooth
Michael addition to quinol carbonate 5 to give the C4-ally-
lated binol 7 as a single product in 95% yield (99% ee).[18,19]
AHCTUNGTRENNUNG
Scheme 4. Introduction of an allyl group to 5.
Further examples are summarized in Table 2. Treatment
of 5 with silylated nucleophiles (TMS-Nu) in the presence of
BF3·OEt2 in CH3CN afforded the C4-functionalized prod-
ucts 8–10 in excellent yields with stereochemical integrity.[20]
Use of Me3SiCl as the nucleophile gave the chlorinated
binol 8 after 24 h reaction (Table 2, entry1). The reactions
Table 2. Introduction of functional groups.
Figure 2. ORTEP diagram of 5. Thermal ellipsoids are drawn at 50%
probability.
Having tethered ortho-quinol carbonate 5 in hand, we ex-
amined its utility for the biaryl elaboration. Scheme 3 shows
the regioselective introduction of a methyl group to 5.
Entry Conditions
Product Yield [%][a] ee [%][b]
1
2
3
4
Me3SiCl,[c] BF3·OEt2,[d]CH3CN,
8
97
99
99
97
99
99
99
99
RT, 24 h
Me3SiN3,[c] BF3·OEt2,[d] CH3CN,
RT, 0.5 h
9
Me3SiCN,[c] BF3·OEt2,[d] CH3CN, 10
RT, 1 h
4-(tBu)C6H4SH,[c] CH2Cl2, 08C,
11
10 min
[a] Yield of isolated product. [b] Assessed by chiral HPLC (see the Sup-
porting Information). [c] 3.0 equiv. [d] 1.0 equiv.
Scheme 3. Introduction of a methyl group to 5.
356
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Chem. Asian J. 2011, 6, 355 – 358

Regioselective Remote Functionalization of Biaryl Framework
with Me3SiN3 or Me3SiCN proceeded more quickly to afford
and the combined organic extracts were washed with brine, dried
(Na2SO4), and concentrated in vacuo. The residue was purified by flash
column chromatography (silica gel) to give 4-allyl-1,1’-bi-2-naphthol 7
(191 mg, 585 mmol, 95%) as a pale yellow foamy solid; m.p. 53.1–54.98C.
1H NMR (400 MHz, CDCl3): d=3.90 (d, 2H, J=6.6 Hz), 5.01 (s, 1H),
5.02 (s, 1H), 5.20 (dd, 1H, J=10.1, 2.9 Hz), 5.23 (dd, 1H, J=17.1,
2.9 Hz), 6.17 (ddt, 1H, J=17.1, 10.1, 6.6 Hz), 7.11–7.17 (m, 2H), 7.23–
7.35 (m, 5H), 7.36 (ddd, 1H, J=8.3, 8.3, 1.2 Hz), 7.83 (d, 1H, J=7.8 Hz),
7.88 (d, 1H, J=9.0 Hz), 8.05 ppm (d, 1H, J=8.3 Hz). 13C NMR
(100 MHz, CDCl3): d=37.3, 109.3, 111.0, 117.0, 117.6, 117.9, 123.8, 123.9,
124.2, 124.3, 124.8, 127.1, 127.3, 128.0, 128.2, 129.3, 131.2, 133.4, 133.8,
136.0, 140.2, 152.3, 152.6 ppm. IR (KBr): n˜ =3498, 3060, 2976, 1618, 1597,
1514, 1382, 1223, 1195, 1180, 1145, 1132, 992, 914, 818, 754 cmꢀ1. Elemen-
tal analysis calcd for C23H18O2: C 84.64, H 5.56; found: C 84.42, H 5.85.
½aꢁ2D2 =+13.6 (c=1.04, CHCl3). HPLC [CHIRALPAC IA (Daisel), 0.46ꢂ
the corresponding azido-binol
9 and cyano-binol 10
(Table 2, entries 2, 3). In sharp contrast to the C4 regioselec-
tivities described above, a thiol was found to react at the C3
position (Table 2, entry 4): Treatment of 4-tert-butylbenzene-
thiol with 5 in CH2Cl2 smoothly gave C3-sulfide 11,[21] as
confirmed by the NOESY correlation (Figure 4). Although
the origin of this distinct regioselectivity is not clear,[22] the
thio functionality will be exploited for installation of various
substituents at the C3 position.[23,24]
250 mm, hexane/2-propanol=6:4, 1.0 mLminꢀ1
10.9 min for 7 (16.2 min for ent-7).
, 208C, 254 nm] tR =
Acknowledgements
Figure 4. NOESY correlation of 11.
We are grateful to Ms. Sachiyo Kubo for X-ray analyses. This work was
supported from Ministry of Education, Culture, Sports, Science, and
Technology, Japan [Grant-in-Aid for Scientific Research on Priority
Areas (No.16073210)] and partially by the Global COE program
(Chemistry). A JSPS fellowship to Y.K. for Young Japanese Scientists is
gratefully acknowledged.
In conclusion, the present procedures will allow access to
various biaryl-2,2’-diol derivatives including, for example,
non-C2-symmetric binol derivatives, potentially versatile
chiral reagents.[12] Further application to the synthesis of nat-
ural products with densely functionalized biaryl structures is
currently underway.
Keywords: biaryls · chirality · ortho-quinol · oxidation ·
regioselectivity
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Experimental Section
Typical procedure for conversion of mono-Boc-binol (4) to ortho-quinol
carbonate 5: A solution of PhIACHTNUGTRENUNG(OCOCF3)2 (1.84 g, 4.27 mmol) in MeCN
(10 mL) was stirred with M.S. 4ꢁ (750 mg) for 1 h. The suspension was
cooled to 08C, to which was added dropwise a solution of 4 (1.50 g,
3.88 mmol) in MeCN (10 mL). After stirring for 10 min at 08C, the mix-
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vacuo. Recrystallization (hexane-acetone) afforded ortho-quinol
5
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(decomp.). 1H NMR (400 MHz, [D6]acetone): d=6.45 (d, 1H, J=
10.0 Hz), 7.05 (brd, 1H, J=8.8 Hz), 7.29 (ddd, 1H, J=8.8, 7.6, 1.2 Hz),
7.38 (dd, 1H, J=7.6, 1.2 Hz), 7.42 (ddd, 1H, J=7.6, 7.6, 1.2 Hz), 7.43
(ddd, 1H, J=8.1, 7.6, 1.2 Hz), 7.45 (d, 1H, J=8.8 Hz), 7.60 (ddd, 1H, J=
7.6, 7.6, 1.2 Hz), 7.79 (dd, 1H, J=7.6, 1.2 Hz), 7.97 (dd, 1H, J=8.1,
1.2 Hz), 8.07 (d, 1H, J=10.0 Hz), 8.13 ppm (d, 1H, J=8.8 Hz). 13C NMR
(100 MHz, [D6]acetone): d=83.8, 113.5, 117.0, 123.8 (2C), 126.3, 128.7,
129.0, 130.0, 130.6, 131.1, 131.6, 131.7, 132.2, 132.4, 133.1, 139.7, 143.7,
148.0, 149.3, 193.7 ppm. IR (ATR): n˜ =1768, 1669, 1635, 1616, 1590, 1567,
1517, 1469, 1437, 1398, 1345, 1282, 1255, 1221, 1204, 1165, 1145, 1129,
1116, 1089, 1042, 1031, 962, 877, 833, 809, 777, 762, 748, 705 cmꢀ1. Ele-
mental analysis calcd for C21H12O4: C 76.82, H 3.86; found: C 76.81,
H 3.88. ½aꢁ2D5 =ꢀ263 (c=1.06, CHCl3). HPLC [CHIRALPAC IA (Daisel),
0.46ꢂ250 mm, hexane/2-propanol=7:3, 1.0 mLminꢀ1, 208C, 254 nm] tR =
14.3 min for 5 (10.8 min for ent-5).
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Chem. Asian J. 2011, 6, 355 – 358
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
357

K. Suzuki, T. Matsumoto et al.
COMMUNICATION
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Received: August 4, 2010
Published online: September 24, 2010
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Chem. Asian J. 2011, 6, 355 – 358