An unexpected intermolecular chiral biaryl coupling reaction induced by a hypervalent iodine(III) reagent: Synthesis of potential precursor for ellagitannin

Article abstract of DOI:10.1039/a809680e

A novel phenyliodine(III) bis(trifluoroacetate) (PIFA)-induced intermolecular chiral biaryl coupling reaction has been accomplished using α-D-glucose derivatives as chiral templates.

Full text of DOI:10.1039/a809680e

An unexpected intermolecular chiral biaryl coupling reaction induced by a
hypervalent iodine(iii) reagent: synthesis of potential precursor for
ellagitannin
Mitsuhiro Arisawa, Saori Utsumi, Makiko Nakajima, Namakkal G. Ramesh, Hirofumi Tohma and Yasuyuki
Kita*
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6, Yamada-oka, Suita, Osaka 565-0871, Japan.
E-mail: kita@phs.osaka-u.ac.jp
Received (in Cambridge, UK) 11th December 1998, Accepted 28th January 1999
A novel phenyliodine(iii) bis(trifluoroacetate) (PIFA)-in-
duced intermolecular chiral biaryl coupling reaction has
been accomplished using a-d-glucose derivatives as chiral
templates.
hypervalent iodine(iii)-induced intramolecular biaryl coupling
reaction of phenol ether derivatives leading to dibenzo hetero-
cyclic compounds has been reported by us.9 The facile nature of
this reaction prompted us to explore the possibility of using
chiral templates in the above coupling reaction with a view to
obtaining optically active biaryl compounds. Here we report the
first example of an asymmetric intermolecular biaryl coupling
reaction induced by phenyliodine(iii) bis(trifluoroacetate)
(PIFA) with a-d-glucose derivatives as the chiral auxiliary.
Our strategy to obtain the chiral biaryl compounds involves
the following three step sequence: (a) synthesis of substituted
aroyl derivatives of chiral diols, (b) biaryl coupling reaction
using hypervalent iodine(iii) reagent and (c) removal of the
chiral auxiliary. Accordingly, aroyl derivatives of diols derived
from glucose, menthane-3,8-diol, pinane-2,3-diol and hydro-
benzoin have been synthesized and their biaryl coupling
reaction examined using PIFA. Interestingly, except for the
glucose-derived diol derivatives, none of the others were found
to participate in the coupling reaction. Thus, the 1,2-diaroyl
derivatives (1a, b)† of protected a-d-glucose underwent a
smooth coupling reaction in the presence of PIFA–BF3•Et2O,
unexpectedly in an intermolecular fashion, to afford the dimers
(2a, b)† in good yields and with high diastereoselectivity
Chiral biaryl compounds serve as important building blocks in
the synthesis of natural products including ellagitannins, which
have diverse pharmacological activities, such as inhibition of
HIV reverse transcriptase,1 DNA topoisomerase I mediated
relaxation2 and antioxidant activity.3 In addition they are also
used as chiral catalysts in asymmetric reactions.4 Although
several kinds of asymmetric biaryl coupling reactions leading to
ellagitannin have been reported,5 most of them involve the use
of heavy metal reagents, such as Pb(OAc)4, CuCN and Cu–
pyridine, affording the products in moderate yields.
In recent years, use of hypervalent iodine(iii) reagents has
gained importance as a non- or low-toxic alternative to heavy
metal reagents, to perform a variety of organic transformations.
In continuation of our research on the use of hypervalent
iodine(iii) reagents in organic synthesis, we reported efficient
nucleophilic substitution reactions on electron-rich aromatic
compounds using a variety of nucleophiles such as N3,6 OAc, b-
dicarbonyl compounds,7 SCN and SPh.8 Very recently, a
Table 1 Novel chiral biaryl coupling reaction using PIFA
R2
R1
O
O
O
O
O
Intramolecular
Reaction
O
OMe
R2
O
R1
O
O
MeO
O
O
O
OMe
OMe
MeO
OMe
MeO
PIFA
O
OMe
O
BF3•Et2O
CH2Cl2
–40 °C
20 min
R2
R3
OMe
OMe
R1
O
O
O
HO
R4
R5
MeO
O
OMe OMe
OMe
O
O
OMe
LiAlH4
1a–f
O
MeO
MeO MeO
Intermolecular
Reaction
THF
quant.
R3
OMe
OMe
R4
R5
MeO
OH
2
(S)-3 >99 % ee
2a–c, e
Run
Substrate
R1
R2
R3
R4
R5
Yield (%)a De (%)
1
2
3
4
5
6
1a
1b
1c
1d
1e
1f
Me
Ph
Me
Me
Me
Me
Ph
H
Ph
Ph
Ph
Ph
OMe
OMe
OEt
OMe
H
OMe
OMe
OEt
H
OMe
H
OMe
OMe
OEt
OMe
OMe
H
79 (90)
44 (68)
37 (59)
0b
30 (38)
0b
> 99
> 99
> 99
—
> 99
—
H
a Yields in parenthesis indicate the conversion yields based upon the consumed starting material. b Complex mixture.
Chem. Commun., 1999, 469–470
469

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Preparation of 2a: To a stirred solution of 1a (34.2 mg, 0.050 mmol) in
(Table 1). It is quite surprising that the reaction proceeds in an
intermolecular fashion and not in the expected intramolecular
way. Even more surprising is that only the aromatic ring
attached to the C-2 carbon of the sugar moiety underwent the
coupling reaction, while the aromatic ring on the C-3 carbon of
the sugar remained intact. However, it has been observed that
the substituent on the C-3 aromatic ring exerts a great influence
on this biaryl coupling reaction. High yields of the products
were obtained in the case where the aromatic ring on the C-3
carbon of the sugar was substituted with three methoxy groups
at the 3’, 4’ and 5’ positions. Bulkier substituents on the C-3
aromatic ring reduce the yield of the desired product, while no
reaction was observed at all with the unsubstituted one.
Noteworthy is that only the a-d-glucopyranoside derivative is
effective in bringing about this coupling reaction. No coupling
reaction took place with the diaroyl derivatives of methyl-b-d-
glucopyranoside. Substituted diaroyl derivatives derived from
other carbohydrate molecules such as galactose or mannose
proved unsuccessful for this reaction. Furthermore, the choice
of the Lewis acid used to activate PIFA seems to be critical.
Among tested Lewis acids such as BF3•Et2O, BF3•Bu2O, BCl3,
ZnBr2, TiCl4, SnCl4, Et2AlCl, FeCl3, MgCl2, Sn(OTf)3 and
TMSOTf, only BF3•Et2O was found to be an efficient activator
in the present case.
CH2Cl2 (0.50 ml) was added a solution of PIFA (21.5 mg, 0.050 mmol) and
BF3•Et2O (0.013 ml, 0.100 mmol) in CH2Cl2 (0.50 ml) at 240 °C under
nitrogen atmosphere, and the reaction was stirred at the same temperature
for 20 min. The reaction was quenched by the addition of saturated
NaHCO3, extracted with CH2Cl2, washed with brine, dried over Na2SO4
and evaporated. After column chromatography (n-hexane–AcOEt = 1:1),
2a (27.0 mg, 0.0197 mmol, 79%) and 1a (4.0 mg, 12%) were obtained as
colorless needles. Selected data for 2a: mp 168.0–170.0 °C (from Et2O);
dH(500 MHz, CDCl3) 1.47 (6H, s), 3.32 (6H, s), 3.45 (6H, s), 3.57–3.63
(4H, m), 3.80 (6H, s), 3.82 (6H, s), 3.91 (6H, s), 3.92 (12H, s), 3.96–4.06
(4H, m), 4.64 (2H, dd, J 9.77, 3.66), 4.75 (2H, d, J 3.66), 5.86 (2H, dd, J
9.77, 9.77), 7.20 (2H, s), 7.33 (4H, s), 7.33–7.37 (10H, m); dC(75.0 MHz,
CDCl3) 31.78, 55.13, 55.65, 56.25, 60.39, 60.82, 60.95, 62.99, 63.73, 70.10,
72.32, 73.01, 97.50, 102.15, 107.06, 109.31, 124.56, 124.54, 125.14,
126.59, 128.13, 128.83, 140.29, 142.65, 145.51, 150.87, 152.03, 153.09,
165.22, 165.41; IR nmax(KBr)/cm21 1728, 1338, 1223 cm21; m/z (FAB)
1366 (M+); HRMS (FAB): calc. for C70H78O28Na 1389.4578, found
1389.4561. Anal. calc. for C70H78O28: C, 61.49; H, 5.75. Found: C, 61.09;
H, 5.73.
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4897.
In order to obtain the chiral biaryl compound, the coupled
adducts (2a–c, e) were treated with LiAlH4. In all cases, the
optically active biphenyl compound (3) was obtained in
quantitative yield, with the regeneration of the chiral sugar
auxiliary, which can be used for successive reactions. The
optical purity of 3 was determined by HPLC to be > 99%,
according to the procedure of Meyers.5d,10
5 (a) K. S. Feldman and S. M. Ensel, J. Am. Chem. Soc., 1993, 115, 1162;
(b) K. S. Feldman, S. M. Ensel and R. D. Minard, J. Am. Chem. Soc.,
1994, 116, 1742; (c) K. S. Feldman and S. M. Ensel, J. Am. Chem. Soc.,
1994, 116, 3357; (d) T. D. Nelson and A. I. Meyers, J. Org. Chem.,
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Chem., 1995, 60, 8171; (g) K. F. Feldman and R. S. Smith, J. Org.
Chem., 1996, 61, 2606; (h) A. I. Meyers, J. Heterocyclic Chem., 1998,
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39, 8943; (j) D. Dai and O. R. Martin, J. Org. Chem., 1998, 63, 7628.
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Tetrahedron Lett., 1991, 32, 4321.
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Sakurai and S. Oka, J. Am. Chem. Soc., 1994, 116, 3684.
8 (a) Y. Kita, T. Takada, S. Mihara and H. Tohma, Synlett, 1995, 211; (b)
Y. Kita, T. Takada, S. Mihara, B. A. Whelan and H. Tohma, J. Org.
Chem., 1995, 60, 7144.
A plausible explanation for this unexpected intermolecular
coupling reaction could be that the sugar moiety and the
trimethoxybenzoyl group present at the C-3 carbon of the sugar
have a spacial interaction, thereby favorably positioning the
aromatic ring on the C-2 carbon to couple with another like
molecule.
In summary, we have encountered an unexpected inter-
molecular biaryl coupling reaction induced by PIFA. The
reaction proceeds in high yields and with remarkable diaster-
eoselectivity. The importance of chiral biaryl compounds in
organic synthesis as well as in biological sciences, coupled with
the use of a hypervalent iodine(iii) reagent as a low-toxic
reagent, render this method attractive for the synthesis of
optically active biphenyl compounds. Detailed investigation of
this interesting reaction is in progress.
9 (a) Y. Kita, M. Gyoten, M. Otsubo, H. Tohma and T. Takada, Chem.
Commun., 1996, 1481; (b) T. Takada, M. Arisawa, M. Gyoten, R.
Hamada, H. Tohma and Y. Kita, J. Org. Chem., 1998, 63, 7698.
10 We followed the protocol of Meyers et al., while determining the ee of
the biphenyl compound 3. According to them [ref. 5(d)] in such cases,
HPLC was found to be a more reliable method for the determination of
ee than by optical rotation. They encountered a discrepancy in the
optical rotation of a similar compound.
Notes and references
† Preparation of 1a: A solution of methyl-4,6-O-(1A-methylbenzylidene)-a-
d-glucopyranoside (ref. 11) (2.22 g, 7.5 mmol), DMAP (183 mg, 1.5 mmol),
DCC (3.25 g, 15.75 mmol) and 3,4,5-trimethoxybenzoic acid (3.18 g, 15.0
mmol) in CH2Cl2 (125 ml) was stirred at room temperature for 12 h. The
precipitate was filtered and the mother liquor was subjected to column
chromatography (n-hexane–AcOEt = 3:2), giving 1a (4.68 g, 6.83 mmol,
91.0 %) as colorless needles. Mixed benzoates 1c–f were synthesized from
methyl-4,6-O-(1A-methylbenzylidene)-2-(3A,4A,5A-trimethoxybenzoyl)-a-d-
glucopyranoside, which in turn was regioselectively prepared from methyl-
4,6-O-(1A-methylbenzylidene)-a-d-glucopyranoside using 1-(benzoyloxy)-
benzotriazole (ref. 12).
11 A. Lipták and P. Pügedi, Angew. Chem., Int. Ed. Engl., 1983, 22,
255.
12 S. Kim, H. Chang and W. J. Kim, J. Org. Chem., 1985, 50, 1751.
Communication 8/09680E
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Chem. Commun., 1999, 469–470