Asymmetric synthesis of axially chiral biaryls via desymmetrization of 2,2′,6,6′-tetrahydroxybiphenyl using 1,4-Di-O-benzyl-L-threitol as a chiral template

Article abstract of DOI:10.1021/jo991364g

Sequential etherification of 2,2′,6,6′-tetrahydroxybiphenyl (1) with 1,4-di-O-benzyl-L-threitol under Mitsunobu conditions gives desymmetrized biphenyldiol 9 of S-axial chirality exclusively. Cyclization of 9 with l, u-dibromoalkanes followed by removal of the chiral auxiliary yields (S)-2,2′-biphenyldiols 14 with alkylenedioxy bridges at the 6 and 6′ positions. (S)-6,6′-Dialkyl- and -diphenyldiols 20 are obtained in an efficient manner via Pd(0)-catalyzed cross-coupling of bis(triflate) derivative 17 with organozinc reagents. Bis(triflate) 17 also serves as an intermediate for asymmetric synthesis of axially chiral biphenyldicarboxylic acid 23, terphenylcarboxylic acid 28, lactone 26, and lactam 30.

Full text of DOI:10.1021/jo991364g

J . Org. Chem. 2000, 65, 1335-1343
1335
Asym m etr ic Syn th esis of Axia lly Ch ir a l Bia r yls via
Desym m etr iza tion of 2,2′,6,6′-Tetr a h yd r oxybip h en yl Usin g
1,4-Di-O-ben zyl-L-th r eitol a s a Ch ir a l Tem p la te
Tran Mai Thi Tuyet, Toshiro Harada,* Kazuyuki Hashimoto, Masanori Hatsuda, and
Akira Oku
Department of Chemistry, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku Kyoto 606-8585, J apan
Received August 27, 1999
Sequential etherification of 2,2′,6,6′-tetrahydroxybiphenyl (1) with 1,4-di-O-benzyl-L-threitol under
Mitsunobu conditions gives desymmetrized biphenyldiol 9 of S-axial chirality exclusively. Cyclization
of 9 with 1,ω-dibromoalkanes followed by removal of the chiral auxiliary yields (S)-2,2′-biphenyldiols
14 with alkylenedioxy bridges at the 6 and 6′ positions. (S)-6,6′-Dialkyl- and -diphenyldiols 20 are
obtained in an efficient manner via Pd(0)-catalyzed cross-coupling of bis(triflate) derivative 17 with
organozinc reagents. Bis(triflate) 17 also serves as an intermediate for asymmetric synthesis of
axially chiral biphenyldicarboxylic acid 23, terphenylcarboxylic acid 28, lactone 26, and lactam
30.
Sch em e 1
In tr od u ction
Axially chiral biaryl compounds have become increas-
ingly important as ligands for a variety of effective chiral
catalysts1 and as pharmacologically potent natural prod-
ucts.2 For this reason, much attention has been focused
on their enantioselective syntheses.3 Most of the reported
methods rely on intra- or intermolecular biaryl-coupling
reactions in which the absolute configuration of the
axially chiral structure is controlled when a stereogenic
biaryl bond is formed. Recently, we introduced a concep-
tually different approach based on asymmetric desym-
metrization4 in which differentiation of enantiotopic
groups of prochiral biaryl compounds leads to the genera-
tion of axial chirality.5,6 Thus, we reported that prochiral
2,2′,6,6′-tetrahydroxybiphenyl (1) is converted to (S)-diols
2 with 69% diastereoselectivity through enantiodifferen-
tiating acetalization with l-menthone (Scheme 1). One
of the advantages of the approach is that desymmetrized
derivatives of tetrol 1 can be transformed to a variety of
biaryl compounds. Indeed, we reported that a series of
substituted 2,2′-biphenyldiols are readily accessible
through the functional group transformation and through
the directed ortho functionalization of (S)-diol 2.
(1) (a) Kagan, H. B.; Riant, O. Chem. Rev. 1992, 92, 1007. (b)
Narasaka, K. Synthesis 1991, 1. (c) Bao, J .; Wulff, W. D.; Rheingold,
A. L. J . Am. Chem. Soc. 1993, 115, 3814 and references therein.
(2) (a) McKee, T. C.; Cardellina, J . H., II; Riccio, R.; D’Auria, M. V.;
Lorizzi, M.; Minale, L.; Mornana, R. A.; Gulakowsi, R. J .; McMahon,
J . B.; Buckheit, R. W., J r.; Snader, K. M.; Boyd, M. R. J . Med. Chem.
1991, 34, 3402. (b) Boyd, M. R.; Hallock, Y. F.; Cardellina, J . H., II;
Manfredi, K. P.; Blunt, J . W.; McMahon, J . B.; Buckheit, R. W., J r.;
Bringmann, G.; Scha¨ffer, M.; Ragg, G. M.; Thomas, D. W.; J ato, J . G.
J . Med. Chem. 1994, 37, 1740.
(3) For the asymmetric synthesis of axially chiral biaryls, see: (a)
Review: Bringmann, G.; Walter, R.; Weirich, R. Angew. Chem., Int.
Ed. Engl. 1990, 29, 977. (b) Review: Bringmann, G.; Walter, R.;
Weirich, R. Methods of Organic Chemistry (Houben-Weyl); Helmchen,
G., Hoffmann, R. W., Mulzer, J ., Schumann, E., Eds.; Georg Thieme
Verlag: Stuttgart, 1995; Vol. E21a, p 567. (c) Hattori, T.; Hotta, H.;
Suzuki, T.; Miyano, S. J . Chem. Soc., Chem. Commun. 1991, 1375. (d)
Hattori, T.; Hotta, H.; Suzuki, T.; Miyano, S. Bull. Chem. Soc. J pn.
1993, 66, 613. (e) Miyano, S.; Koike, N.; Hattori, T. Tetrahedron:
Asymmetry 1994, 5, 1899. (f) Moorlag, H.; Meyers, A. I. Tetrahedron
Lett. 1993, 34, 6989. (g) Moorlag, H.; Meyers, A. I. Tetrahedron Lett.
1993, 34, 6993. (h) Nelson, T. D.; Meyers, A. I. J . Org. Chem. 1994,
59, 2655. (i) Nelson, T. D.; Meyers, A. I. Tetrahedron Lett. 1994, 35,
3259. (j) Meyers, A. I.; McKennon, M. J . Tetrahedron Lett. 1995, 36,
5869. (k) Meyers, A. I.; Meir, A.; Rawson, D. J . Tetrahedron Lett. 1992,
33, 853. (l) Shindo, M.; Koga, K.; Tomioka, K. J . Am. Chem. Soc. 1992,
114, 8732. (m) Uemura, M.; Kamikawa, K. J . Chem. Soc., Chem.
Commun. 1994, 2697. (n) Kamikawa, K.; Watanabe, T.; Uemura, M.
Synlett 1995, 1040. (o) Watanabe, T.; Kamikawa, K.; Uemura, M.
Tetrahedron Lett. 1995, 37, 6695. (p) Kamikawa, K.; Watanabe, T.;
Uemura, M. J . Org. Chem. 1996, 61, 1375. (q) Osa, T.; Kashiwagi, Y.;
Yanagisawa, Y.; Bobbitt, J . M. J . Chem. Soc., Chem. Commun. 1994,
2535. (r) Itoh, T.; Chika, J .; Shirakami, S.; Ito, H.; Yoshida, T.; Kubo,
Y.; Uenishi, J . J . Org. Chem. 1996, 61, 3700. (s) Nakajima, M.; Miyoshi,
I.; Kanayama, K.; Hashimoto, S.; Noji, M.; Koga, K. J . Org. Chem.
1999, 64, 2264.
Although asymmetric desymmetrization through ac-
etalization with l-menthone is straightforward, formation
of the diastereotopic byproducts that should be removed
proved particularly problematic upon scale-up. Herein,
we wish to report a general and practical method for
the asymmetric synthesis of axially chiral biaryls via
asymmetric desymmetrization of tetrol 1 using 1,4-
di-O-benzyl-L-threitol as a chiral template. The desym-
(4) (a) Harada, T.; Ueda, S.; Yoshida, T.; Inoue, A, Takeuchi, M.;
Ogawa, N.; Oku, A. J . Org. Chem. 1994, 59, 7575. (b) Harada, T.;
Yoshida, T.; Inoue, A.; Takeuchi, M.; Oku, A. Synlett 1995, 283. (c)
Harada, T.; Ueda, S.; Tuyet, T. M. T.; Inoue, A.; Fujita, K.; Takeuchi,
M.; Ogawa, N.; Oku, A.; Shiro, M. Tetrahedron 1997, 53, 16663-78.
(5) For a similar approach, see: Hayashi, T.; Niizuma, S.; Kami-
kawa, T.; Suzuki, N.; Uozumi, Y. J . Am. Chem. Soc. 1995, 117, 9101.
(6) (a) Ward, R. S. Chem. Soc. Rev. 1990, 19, 1. (b) Gais, H.-J .
Methods of Organic Chemistry (Houben-Weyl); Helmchen, G., Hoff-
mann, R. W., Mulzer, J ., Schumann, E., Eds.; Georg Thieme Verlag:
Stuttgart, 1995; Vol. E21a, p 589. (c) Harada, T.; Oku, A. Synlett 1994,
95. (d) Vedejs, E.; Daugulis, O.; Diver, S. T. J . Org. Chem. 1996, 61,
430 and references therein.
10.1021/jo991364g CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/09/2000

1336 J . Org. Chem., Vol. 65, No. 5, 2000
Tuyet et al.
Sch em e 2
F igu r e 1.
metrization proceeds stereoselectively without forming
diastereotopic byproducts and the resulting chiral biaryl-
diol 9 serves as a versatile intermediate for asymmetric
synthesis of biaryl compounds possessing not only hy-
droxy but also other functionalities.7
metrization. The chiral diol was prepared from L-tartaric
acid according to the reported procedure11 and was
converted to the monosilyl ether 5 in 77% yield. Mit-
sunobu etherification of tetrol 1 with 5 using DEAD
proceeded with inversion of stereochemistry to give
monoether 7 in 94% yield. Deprotection of 7 (97%) and
subsequent cyclization under the Mitsunobu conditions
using dimethyl azodicarboxylate (DMAD)12 furnished
desymmetrization product 9 with S-axial chirality and
with (R,R)-auxiliary group13 exclusively as colorless
crystals in 90% yield.
To gain information on the origin of high stereoselec-
tivity observed, MO (PM3)14 calculations were carried out
for dimethyl derivative 8 and the corresponding diaste-
reomer 10 (Figure 1). The calculations showed that 8A
and 10A are the most stable conformers for 8 and 10,
respectively. Conformer 8A was calculated to be 2.57
kcal/mol more stable than conformer 10A. Both conform-
ers have a similar C2-symmetrical conformation of the
1,4-dioxocane ring. Two methyl groups in 8A locate
approximately in the gauche position (a dihedral angle
Me-C-C-Me ) 67°). On the other hand, the deviation
of the two groups from the anti position is considerable
for 10A (dihedral angle Me-C-C-Me ) -145°), sug-
gesting that a repulsive interaction between the benzene
ring and the methyl group is the major factor for the
unstability of 10A. It is most likely that the stereoselec-
tivity of the second Mitsunobu cyclization is controlled
kinetically. Assuming an SN2-type transition-state model
11 and 12,10b the exclusive formation of 8 or 9 through
11 can be rationalized by a similar, but more pronounced,
unfavorable interaction between the R (Me or BnOCH2)
group and the benzene ring in 12.
Resu lts a n d Discu ssion
Recently, Lipshutz et al. have reported a highly ste-
reoselective intramolecular coupling of 3 where two aryl
units are connected through a chiral 1,2-dioxy moiety (eq
1).8,9 Their report prompted us to examine a possible use
of a chiral 1,2-diol as a template in asymmetric desym-
metrization of tetrol 1. To assess the degree of stereo-
selectivity, we first examined desymmetrization of 1 by
using (2R*,3R*)-2,3-butanediol (Scheme 2). Treatment of
tetrol 1 with mono-TBS derivative 4 under the conditions
of the Mitsunobu etherification10 (diethyl azodicarbox-
ylate (DEAD), PPh3, THF) afforded monoether 6 in 52%
yield. After deprotection of the TBS group with Bu4NF
(80% yield), the resulting alcohol was again subjected to
the Mitsunobu reaction. The intramolecular cyclization
proceeded smoothly to give 8 in 67% yield. Stereoselec-
tivity of the cyclization was high; formation of the
1
diastereomer was not detected by H NMR analysis of
the crude product.
Intermolecular cyclization of diol 9 with 1,ω-dibromo-
alkanes in the presence of K2CO3 in DMF gave biphenyls
13a -e with -O(CH2)nO- (n ) 4, 5, 6, 7, and 10) bridges
(eq 2, Table 1). The reactions were carried out under high
dilution conditions by adding the dibromoalkanes slowly
during 5-6 h at 80 °C by using a syringe pump. It should
Being encouraged by high selectivity observed, we then
examined the use of (2S,3S)-1,4-di-O-benzyl-L-threitol
as a chiral template that can be removed after desym-
(7) For a preliminary report of a portion of this work, see: Harada,
T.; Tuyet, T. M. T.; Hashimoto, K.; Hatsuda, M.; Oku, A. Synlett 1997,
1246.
(8) (a) Lipshutz, B. H.; Kayser, F.; Liu, Z.-P. Angew. Chem., Int. Ed.
Engl. 1994, 33, 1842. (b) Lipshutz, B. H.; Li, Z.-P.; Kayser, F.
Tetrahedron Lett. 1994, 35, 5567. (c) Lipshutz, B. H.; J ames, B.; Vance,
S.; Carrico, I. Tetrahedron Lett. 1997, 38, 753.
(11) Mash, E. A.; Nelson, K. A.; Densen, E. V.; Hemperly, S. B.
Organic Syntheses; Wiley: New York, 1993; Collect. Vol. VIII, p 155.
(12) DMAD in place of DEAD has an advantage that byproduct
hydrazine can be removed by aqueous extraction. We would like to
thank Professor Toshikazu Takata of Osaka Prefecture University for
this information.
(9) (a) Rawal, V. H.; Florjancic, A. S.; Singh, S. P. Tetrahedron Lett.
1994, 35, 8985. (b) Lin, G.-Q.; Zhong, M. Tetrahedron Lett. 1997, 38,
1087.
(10) (a) Mitsunobu, O. Synthesis 1981, 1. (b) Hughes, D. L. Org.
React. 1992, 42, 335.
(13) The absolute configuration of the chiral template L-threitol
derivative undergoes inversion through sequential Mitsunobu etheri-
fication. The term “chiral auxiliary” used through out this paper
indicates the resulting template-derived moiety of (R,R)-configuration.
(14) Stewart, J . J . P. J . Comput. Chem. 1989, 10, 209, 221.

Asymmetric Synthesis of Axially Chiral Biaryls
J . Org. Chem., Vol. 65, No. 5, 2000 1337
Ta ble 1. Asym m etr ic Syn th esis of (S)-Bip h en yld iols
14a -e
Sch em e 3
etherification
removal of auxiliary
entry
n
product yield (%) product yield (%) ee (%)
1
2
3
4
5
4
5
6
7
10
13a
13b
13c
13d
13e
84
77
73
53
29
14a
14b
14c
14d
14e
100
95
99
100
92
98a
>95b
>95b
98a
>95b
a
Ee was determined by LC analysis using a Chiracel OD
column. Ee was determined by 1H NMR analysis of the mono-
b
MTPA derivatives.
be noted that the efficiency of the cyclization is higher
than that observed in a related reaction of acetal deriva-
tive 2.5c Thus, for example, hexamethylenedioxy deriva-
tive 13c was obtained in 73% yield (entry 3), while under
similar conditions, the reaction of acetal 2 with 1,6-
dibromohexane gave the corresponding product in 56%
yield. Even 16-membered macrocyclic product 10e with
a decamethylenedioxy bridge could be prepared albeit in
lower yield (entry 5). The improvement in the yields is
probably due to the wider biaryl torsional angle in 9 in
comparison with that in 2.
Sch em e 4
The chiral auxiliary in cyclization products 13a -e
could be removed efficiently in two steps. Thus, hydro-
genolysis (H2, 10% Pd/C, EtOH) and treatment of the
potassium alkoxides of the resulting diols in DMSO at
50 °C furnished (S)-biphenyldiols 14a -e15 of high enan-
tiomeric purities in high yields (Table 1). Use of the
potassium salts in DMSO is essential. When sodium as
a counterion or THF as a solvent was employed, the
reaction was sluggish, and prolonged heating at higher
temperatures resulted in considerable racemization of the
products.16
Palladium- and nickel-catalyzed cross-coupling is one
of the efficient methods for the preparation of regio-
selectively substituted arenes.17 Recent advances in the
successful use of aryl triflates as substrates has expanded
the utility of the reaction18 because of the diversity of
available hydroxyarenes and the simple conversion of
them to aryl triflates.19 In our previous work, we exam-
ined cross-coupling of bis(triflate) 15 (Scheme 3).5b Al-
though dimethylation of 15 with MeZnCl proceeded
efficiently in the presence of NiCl2(dppp), the reaction
with other organometallics such as Et2Zn, EtMgBr, and
PhZnCl did not afford the corresponding coupling prod-
ucts in appreciable yields. The biaryl moiety in 15 is fixed
with a relatively narrow torsional angle, and the reaction
may be hampered due to steric hindrance. We anticipated
that bis(triflate) 17 with a larger torsional angle pos-
sesses higher reactivity in cross-coupling and may serve
as a versatile intermediate for asymmetric synthesis of
axially chiral biaryldiols.
Bis(triflate) 17 was prepared in 90% yield by the
treatment of biphenyldiol 9 with triflic anhydride in
pyridine (Scheme 4). Cross-coupling of 17 with MeZnCl
(6 equiv) was first examined in the presence of NiCl2-
(dppp) (40 mol %) in refluxing THF. The reaction gave
dialkylation product 18a 20 and the monoalkylation prod-
uct 19a in 65% and 12% yields, respectively, together
with recovery of 17 (Table 2, entry 1). Under these
conditions, reaction with Me2Zn also gave a similar result
(entry 2). On the other hand, reaction with EtZnCl was
sluggish, affording diethylation product 18b only in 5%
(15) Absolute configuration of 14a -c was confirmed by comparing
their specific rotations to those reported previously.5c
(16) For the thermal stability of axial chirality of 14, see ref 5c.
(17) Tsuji, J . Palladium Reagents and Catalysts; Wiley: New York,
1995. (b) Heck, R. F. Palladium Reagents in Organic Synthesis;
Academic Press: New York, 1985.
(19) Stang, P. J .; Hanack, H. Subramanian, L. R. Synthesis 1982,
(18) Review: Ritter, K. Synthesis 1993, 735.
85.

1338 J . Org. Chem., Vol. 65, No. 5, 2000
Tuyet et al.
Ta ble 2. Cr oss-Cou p lin g Rea ction of Bis(tr ifla te) 17a
Ta ble 4. P a lla d iu m -Ca ta lyzed Cya n a tion of Bis(tr ifla te)
17a
yield (%)
mol time
product yield (%)
concentration
entry reagent
catalyst
MeZnCl NiCl2(dppp)
Me2Zn NiCl2(dppp)
EtZnCl NiCl2(dppp)
Et3B
%
(h) 18a ,b 19a ,b 17
entry
(M)
T (°C)
21
22
17
1
2
40
40
40
18
16
23
20
65
56
5
12
13
20
35
5
7
70
11
1
2
0.5
0.8
1.0
0.8
120
120
150
120
43
50
86
18
37
32
15
10
3
4b
PdCl2(dppf)c 10
34
3
4b
44
38
a
All reactions were carried out at 65 °C in THF by using an
b
a
organozinc reagent (6 equiv) or Et3B (5 equiv). K3PO4 (3 equiv)
and KBr (2.5 equiv) was used. c The catalyst was treated with
DIBALH before use.
Unless otherwise noted, reactions were carried out by using
2.0 equiv of Zn(CN)2 and 10 mol % of Pd(PPh3)4 in DMF for 16 h.
b
The reaction was carried out by using 3 mol % of Pd(PPh3)4 for
3 h.
Ta ble 3. P a lla d iu m -Ca ta lyzed Cr oss-Cou p lin g Rea ction
of Bis(tr ifla te) 17 w ith Or ga n ozin c Rea gen tsa
two steps (Scheme 3).5b From the preparative point of
view, the present method is considerably more straight-
forward than the previous one. In the cross-coupling of
16, reduction of the TfO group took place as a side
reaction.5b The absence of such reduction byproducts is
another advantage of the present method.
mol % of
time
(h)
yield
(%)
entry reagent equiv PdCl2(dppf)
product
1
2
3
4
EtZnCl
EtZnCl
Et2Zn
6
3
6
6
4
6
3
4
4
10
5
10
10
5
5
5
5
5
17
37
18
45
20
15
23
20
24
18b
100
96
66
95
99
94
5
Et2Zn
Recently, it has been revealed that cyanation25 as well
as amination26 of aryl triflates is catalyzed also by
palladium complexes. We anticipated that bis(triflate) 17
may also serve as an intermediate for the asymmetric
synthesis of functionalized biphenyls by using these
reactions. Cyanation reaction of 17 was carried out by
using Zn(CN)2 in combination with Pd(PPh3)4 (10 mol %)
in DMF (eq 3, Table 4).25c Although a considerable
amount of monocyano derivative 22 was produced as a
byproduct in the reaction at 0.5 M at 120 °C (entry 1),
dicyano derivative 21 was obtained in higher yield in
similar reactions at higher concentration (entry 2). The
best yield of 86% was achieved when the reaction was
carried out at 1.0 M at 150 °C for 16 h (entry 3). Because
monocyano derivative 22 shows a reactivity similar to
that of 17, it was difficult to obtain 22 selectively,
especially at higher conversion. Reaction for 3 h with a
reduced amount of the catalyst gave 21 in 44% yield with
the 38% recovery of 17 (entry 4).
5b
6b
7c
8
MeZnCl
Me2Zn
Me2Zn
BuZnCl
PhZnCl
18a
18c
18d
90
89
9
a
b
All reactions were carried out in THF at 66 °C. PdCl2(dppf)
was treated with DIBALH before the coupling reaction. c Mono
methylation product 19 was in 20% yield together with the
recovery of 17 (65%).
yield (entry 3). The Suzuki-Miyaura cross-coupling21
of 17 with Et3B also did not give a satisfactory result
(entry 4).
Hayashi et al. reported that PdCl2(dppf) is an efficient
catalyst for cross-coupling of bromoarenes with organo-
zinc reagents.22 We found that dialkylation of bis(triflate)
17 also proceeds in an efficient manner by using PdCl2-
(dppf) in combination with organozinc reagents (Table
3). Thus, 18b was obtained in quantitative yield when
17 was treated with EtZnCl (6 equiv) and PdCl2(dppf)
(10 mol %) in refluxing THF for 17 h (entry 1). Amounts
of the organozinc reagent and the catalyst could be
reduced to 3 equiv and 5 mol %, respectively, by carrying
out the reaction for a longer time (entry 2). Cross-
coupling with Et2Zn was slightly slow but gave 18b also
in high yield (entry 4). PdCl2(dppf)-catalyzed cross-
coupling was equally applicable to other alkylzinc (entries
5-8) and arylzinc reagents (entry 9) to give the corre-
sponding products 18a ,c,d in high yields. For generation
of an active Pd(0) complex, pretreatment of PdCl2(dppf)
with DIBALH was required in the reaction with MeZnCl
and Me2Zn (e.g., entries 6 vs 7).
6,6′-Disubstituted (S)-biphenyldiols 20a -d were pre-
pared in a single step by removing the chiral auxiliary
from 18a -d . Thus, treatment of 18a -d with BBr3 in
CH2Cl2 at room temperature for 20 h furnished enantio-
merically pure (>95% ee) 20a -d 23 in high yields (20a ,
100%; 20b , 76%; 20c, 77%; 20d , 83%). We have pre-
viously reported asymmetric synthesis of 20 via the
Suzuki-Miyaura cross-coupling of 6,6′-dimethoxy bis-
(triflate) 16, which was prepared from bis(triflate) 15 in
Treatment of dicyano derivative 21 with aqueous KOH
in refluxing ethoxyethanol for 10 h gave dicarboxylic acid
23 and amidocarboxylic acid 24 in 47% and 38% yield,
respectively (eq 4). Prolonged reaction did not improve
the yield of 23. However, a separate treatment of 24
under similar conditions afforded 23 in 72% yield. Hydro-
lysis of monocyano derivative 22 proceeded effectively to
give hydroxycarboxylic acid 25 (eq 5). Since 25 was prone
to be converted to lactone 26 during isolation by silica
gel column chromatography, it was isolated as the lactone
(24) Kanoh, S.; Tamura, N.; Motoi, M. Suda, H. Bull. Chem. Soc.
J pn. 1987, 60, 2307.
(20) X-ray analysis performed on 18a further verified the S-axial
chirality of the desymmetrization product 9. See the Supporting
Information for details.
(21) Oh-e, T.; Miyaura, N.; Suzuki, A. J . Org. Chem. 1993, 58, 2201.
(22) Hayashi, T.; Konishi, M.; Kobori, Y.; Kumada, M.; Higuchi, T.;
Hirotsu, K. J . Am. Chem. Soc. 1984, 106, 158.
(25) (a) Takagi, K.; Sakakibara, Y. Chem. Lett. 1989, 1957. (b)
Anderson, B. A.; Bell, E. C.; Ginah, F. O.; Harn, N. K.; Pagh, L. M.;
Wepsiec, J . P. J . Org. Chem. 1998, 63, 8224 and references therein.
(c) Kubota, H.; Rice, K. C. Tetrahedron Lett. 1998, 39, 2907.
(26) (a) Wolfe, J . P.; Buchbald, S. L. J . Org. Chem. 1997, 62, 1264.
(b) Louie, J .; Driver, M. S.; Hamann, B. C.; Hartwig, J . F. J . Org. Chem.
1997, 62, 1268. (c) A° hman, J .; Buchwald, S. L. Tetrahedron Lett. 1997,
38, 6363.
(23) The absolute configuration of 20a ,b was confirmed by compar-
ing their specific rotations to those reported previously.5b,24

Asymmetric Synthesis of Axially Chiral Biaryls
J . Org. Chem., Vol. 65, No. 5, 2000 1339
after treatment of the crude product with p-TsOH in
toluene (80% overall yield).
Palladium-catalyzed cross-coupling of monocyano de-
rivative 22 followed by hydrolysis would afford axially
chiral 2′-substituted biphenylcarboxylic acids. Indeed,
PdCl2(dppf)-catalyzed cross-coupling of 22 with PhZnCl
gave terphenyl 27 in 95% yield (eq 6). Although the cyano
group of 27 is sterically hindered due to the neighboring
phenyl group, hydrolysis of 27 proceeded smoothly to give
terphenylcarboxylic acid 28 in 55% yield.
We have described a practical and general method for
asymmetric synthesis of axially chiral biaryl compounds
based on asymmetric desymmetrization. Sequential ether-
ification of 2,2′,6,6′-tetrahydroxybiphenyl (1) with 1,4-
di-O-benzyl-L-threitol under the Mitsunobu conditions
gave desymmetrized biphenyldiol 9 of S-axial chirality
exclusively. Biphenyldiol 9 was proved to be a versatile
intermediate for asymmetric synthesis of a variety of
biaryl compounds. Cyclization of 9 with 1,ω-dibromoal-
kanes followed by removal of the chiral auxiliary yielded
(S)-2,2′-biphenyldiols 14a -e with alkylenedioxy bridges
at the 6 and 6′ positions. (S)-6,6′-Dialkyl- and (S)-6,6′-
dialkylbiphenyldiol 20a -d could be prepared in an
efficient manner via PdCl2(dppf)-catalyzed cross-coupling
of bis(triflate) derivative 17 with organozinc reagents. It
was also demonstrated that bis(triflate) 17 serves as an
intermediate for asymmetric synthesis of axially chiral
biphenyldicarboxylic acid 23, terphenylcarboxylic acid 28,
lactone 26, and lactam 30.
Exp er im en ta l Section
Gen er a l Meth od s. Unless otherwise noted, 1H and 13C
NMR spectra were recorded in CDCl3 at 300 and 75.6 MHz,
respectively. All commercially available reagents were used
without further purification unless otherwise noted. THF and
toluene were distilled from sodium benzophenone ketyl. DMF,
DMSO, and pyridine were distilled from CaH2. Commercial
anhydrous ZnCl2 was dried in vacuo at 100 °C for 10 h over
P2O5. All reactions were performed under nitrogen or argon
atmosphere. Organic extracts were dried over Na2SO4. Flash
chromatography was conducted on silica gel (Wakogel C-300).
(2S,3S)-1,4-Diben zyloxy-3-(ter t-bu tyld im eth ylsiloxy)-
2-bu ta n ol (5). To a solution of 1,4-di-O-benzyl-L-threitol11
(9.07 g, 30.0 mmol) and imidazole (2.94 g, 43.2 mmol) in DMF
(30 mL) was added tert-butyldimethylchlorosilane (5.65 g, 37.5
mmol) at room temperature. After being stirred for 3 h, the
reaction mixture was poured into water and extracted three
times with ether. The dried organic layers were concentrated
in vacuo. The residue was purified by flash chromatography
Axially chiral biphenyls with 2′-amino and 2-carboxylic
acid groups is of interest as a new type amino acid
component for peptide synthesis and as chiral ligands.
To convert monocyano derivative 22 to the corresponding
amino acid, palladium-catalyzed amination was exam-
ined under the conditions reported by Buchwald et al.26c
When 22 was treated with benzylamine in the presence
of Pd(OAc)2 (5 mol %), (S)-BINAP (7.5 mol %), and Cs2-
CO3 in toluene at 100 °C, a normal amination product
was not produced at all but cyclic amidine 29 was
obtained unexpectedly in 57% yield. The formation of 29
can be explained by the initial reaction of benzylamine
at the cyano group to form intermediates 31 and/or 31′,
which undergo intramolecular cross-coupling to give 29.
The structure of the product was verified by the fact that
hydrolysis under basic conditions afforded lactam 30 in
67% yield. Unfortunately, 30 is rather stable, and the
formation of amino acid derivative was not detected
under these conditions.
1
(5-30% ethyl acetate in hexane) to give 9.39 g (75%) of 5: H
NMR δ 0.05 (3H, s,), 0.06 (3H, s), 0.87 (9H, s), 2.47 (1H, d,
J ) 7.8 Hz), 3.46 (1H, dd, J ) 5.7, 9.3 Hz), 3.49 (2H, d, J )
6.3 Hz), 3.58 (1H, dd, J ) 6.0, 9.3 Hz), 3.87 (1H, m), 3.98 (1H,
dt. J ) 2.7, 6.0 Hz), 4.51 (2H, s), 4.54 (2H, s), 7.25-7.34 (10H,
m); IR (liquid film) 3470 (br), 1100, 835, 700 cm-1
.

1340 J . Org. Chem., Vol. 65, No. 5, 2000
Tuyet et al.
6′-[(1R,2S)-4-Ben zyloxy-2-(ter t-bu tyld im eth ylsilyloxy)-
1-(ben zyloxym eth yl)p r op yloxy]-2,2′,6-bip h en yltr iol (7).
To a solution of biphenyltetrol 127 (1.75 g, 8.00 mmol),
monosilyl ether 5 (4.02 g, 9.65 mmol), and triphenylphosphine
(3.15 g, 12.0 mmol) in THF (60 mL) at 0 °C was slowly added
a THF (20 mL) solution of diethyl azodicarboxylate (DEAD)
(1.9 mL, 12 mmol) during 3 h. After the addition, the mixture
was stirred further at 0 °C for 1 h and then at 40 °C for 14 h.
The mixture was poured into water, acidified with 1 N aqueous
HCl, and extracted twice with ethyl acetate. The dried organic
layers were concentrated in vacuo. Purification of the residue
by flash chromatography (20-50% ethyl acetate in hexane)
gave 4.64 g (94%) of 7: 1H NMR δ -0.17 (3H, s), -0.71 (3H,
s), 0.75 (9H, s), 3.38 (2H, d J ) 5.5 Hz), 3.61 (1H, dd, J ) 7.2,
10.8 Hz), 3.68 (1H, dd, J ) 3.1, 10.8 Hz), 3.98 (1H, br q, J )
ca. 4 Hz), 4.38 (1H, d, J ) 11.7 Hz), 4.43 (2H, s), 4.58 (1H, d,
J ) 11.7 Hz), 4.76 (1H, dt, J ) 3.6, 7.4 Hz), 5.03 (2H, s), 5.67
(1H, s), 6.62 (1H, br d, J ) 7.9 Hz), 6.65 (1H, br d, J ) 7.9
Hz), 6.72 (1H, d, J ) 8.2 Hz), 6.79 (1H, d, J ) 8.2 Hz), 7.15-
484.1886. Anal. Calcd for C30H28O6: C, 74.36; H, 5.82. Found:
C, 74.61; H, 5.72.
Cyclization product 8 was prepared from 6 via 6′-[(1R*,2S*)-
2-hydroxy-1-methylpropyloxy]-2,2′,6-biphenyltriol in 54% over-
all yield by a procedure similar to that described above.
6′-[(1R*,2S*)-2-Hydroxy-1-methylpropyloxy]-2,2′,6-biphenyl-
triol: 1H NMR δ 1.00 (3H, d, J ) 6.3 Hz), 1.18 (3H, d, J ) 6.3
Hz), 2.2 (1H, br), 3.82 (1H, m), 4.38 (1H, dq, J ) 2.9, 6.3 Hz),
4.9 (1H, br), 5.1 (1H, br), 5.35 (1H, br), 6.62 (1H, d, J ) 8.5
Hz), 6.64 (1H, d, J ) 8.5 Hz), 6.65 (1H, d, J ) 8.5 Hz), 6.74
(1H, d, J ) 8.5 Hz), 7.23 (1H, t, J ) 8.4 Hz), 7.33 (1H, t, J )
1
8.2 Hz). Cyclization product 8: H NMR δ 1.36 (6H, m), 3.89
(2H, m), 6.78 (2H, d, J ) 8.1 Hz), 6.80 (2H, d, J ) 8.4 Hz),
7.25 (2H, t, J ) 8.2 Hz); FT-IR (KBr disk) 3300 (br), 1052,
793, 754, 721 cm-1. Anal. Calcd for C16H16O4: C, 70.57; H, 5.92.
Found: C, 70.55; H, 6.04.
Gen er a l P r oced u r e for In ter m olecu la r Cycliza tion of
9. To a solution of 9 (1.0 mmol) in DMF (25 mL) at room
temperature was added K2CO3 (2.3 mmol). A solution of a 1,ω-
dibromoalkane (1.0 mmol) in DMF (10 mL) was added slowly
to the resulting suspension during 5-6 h at 80 °C by using a
syringe pump. The reaction mixture was stirred further for 3
h at this temperature. The resulting mixture was poured into
water and extracted twice with benzene. The dried organic
layers were concentrated in vacuo. Purification of the residue
by flash chromatography (10-30% ethyl acetate in hexane)
gave 6,6′-alkylenedioxy derivatives 13a -e.
7.35 (12H, m); IR (neat film) 3420 (br), 835, 780, 735, 700 cm-1
.
6′-[(1R*,2S*)-2-(tert-Butyldimethylsilyloxy)-1-methylpropyl-
oxy]-2,2′,6-biphenyltriol (6) was prepared from tetrol 1 and
TBS ether 4 in 52% yield by a procedure similar to that
described above. 6: 1H NMR δ -0.09 (3H, s), 0.01 (3H, s), 0.81
(9H, s), 1.01 (3H, d, J ) 6.3 Hz), 1.18 (3H, d, J ) 6.3 Hz), 3.74
(1H, dq, J ) 4.2, 6.3 Hz), 4.29 (3H, dq, J ) 4.2, 6.3 Hz), 4.85
(1H, br s), 4.98 (1H, br s), 5.44 (1H, br s), 6.63 (1H, br d, J )
ca. 8 Hz), 6.65 (1H, br d, J ) ca. 8 Hz), 6.67 (1H, br d, J ) ca.
8 Hz), 6.71 (1H, br d, J ) ca. 8 Hz), 7.22 (1H, t, J ) 8.4 Hz),
7.31 (1H, t, J ) 8.4 Hz).
6,6′-Tetr a m eth ylen ed ioxy d er iva tive 13a : 1H NMR δ
1.75-2.0 (4H, m), 3.63 (2H, br d, J ) ca. 10 Hz), 3.74 (2H, br
d, J ) ca. 10 Hz), 4.1-4.25 (4H, m), 4.44 (2H, br d, J ) ca. 11
Hz), 4.60 (4H, br s), 6.87 (2H, d, J ) 8.7 Hz), 6.89 (2H, d, J )
8.7 Hz), 7.25-7.35 (12H, m); 13C NMR δ 26.90, 70.47, 70.88,
73.49, 84.87, 111.67. 115.18, 118.85, 127.49, 127.53, 128.27,
128.89, 138.03, 157.82, 159.74; IR (neat film) 1060, 790, 725,
695 cm-1; MS m/z (relative intensity) 538 (M+, 23), 355 (70),
192 (100); HRMS calcd for C34H34O6 538.2356, found 538.2366.
6,6′-P en ta m eth ylen ed ioxy d er iva tive 13b: 1H NMR δ
1.67 (2H, m), 1.82 (4H, m), 3.62 (2H, m), 3.73 (2H, m), 4.11
(4H, m), 4.29 (2H, m), 4.58 (4H, s), 6.76 (2H, d, J ) 8.4 Hz),
6.83 (2H, d, J ) 8.1 Hz), 7.25 (2H, t, J ) 8.2 Hz), 7.3-7.35
(10H, m); 13C NMR δ 24.99, 26.56, 67.72, 70.69, 73.64, 84.98,
107.97, 114.29, 117.30, 127.56, 127.64, 128.35, 128.99, 138.13,
Cycliza t ion P r od u ct 9. To a solution of 7 (4.22 g, 6.84
mmol) in THF (34 mL) at 0 °C was added Bu4NF (14 mL, 1 M
in THF, 14 mmol). After being stirred at room temperature
for 4 h, the reaction mixture was poured into 1 N aqueous HCl
and extracted three times with ethyl acetate. The dried organic
layers were concentrated in vacuo. Purification of the residue
by flash chromatography (50-70% ethyl acetate in hexane)
1
gave 3.33 g (97%) of the desilylation product: H NMR δ 2.6
(1H, br), 3.36 (1H, dd, J ) 6.6, 9.8 Hz), 3.45 (1H, dd, J ) 4.1,
9.8 Hz), 3.64 (1H, dd, J ) 5.8, 10.8 Hz), 3.72 (1H, dd, J ) 3.8,
10.8 Hz), 3.92 (1H, dt, J ) 4.1, 5.9 Hz), 4.42 (4H, br s), 4.57
(1H, dt, J ) 4.0, 5.8 Hz), 5.2 (3H, br), 6.59 (1H, br d, J ) 8.2
Hz), 6.62 (1H, br d, J ) 8.2 Hz), 6.73 (2H, d, J ) 8.3 Hz), 7.1-
7.35 (12H, m); 13C NMR δ 62.25, 68.81, 69.93, 70.12, 73.28,
78.35, 106.42, 107.37, 107.78, 108.62, 108.85, 109.68, 127.56,
127.63, 127.69, 127.77, 128.31, 128.31, 130.13, 130.63, 137.50,
137.69, 154.60, 155.05, 155.51, 156.95; IR (KBr disk) 3250 (br),
780, 740, 700 cm-1; MS m/z (relative intensity) 502 (M+, 68),
411 (16), 291 (23), 218 (100); HRMS calcd for C30H30O7
502.1992, found 502.1984.
156.95, 159.84; IR (KBr disk) 1185, 780, 740, 725, 700 cm-1
;
MS m/z (relative intensity) 552 (M+, 78), 444 (12), 200 (55),
91 (100); HRMS calcd for C35H36O6 552.2512, found 552.2506.
6,6′-Hexa m eth ylen ed ioxy d er iva tive 13c: 1H NMR δ
1.54 (4H, m), 1.72 (4H, m), 3.60 (2H, m), 3.71 (2H, m), 3.98
(2H, m), 4.1-4.4 (4H, m), 4.57 (4H, s), 6.73 (2H, d, J ) 8.3
Hz), 6.82 (2H, d, J ) 8.0 Hz), 7.2-7.35 (12H, m); 13C NMR δ
24.06, 25.95, 66.64, 70.76, 73.65, 85.15, 106.82, 113.84, 117.41,
127.57, 127.65, 128.35, 129.12, 138.13, 156.95, 159.93; IR (KBr
disk) 1060, 785, 740, 700 cm-1; MS m/z (relative intensity) 566
(M+, 75), 367 (25), 91 (100); HRMS calcd for C36H38O6 566.2669,
found 566.2661.
To a solution of the desilylation product (2.45 g, 4.87 mmol)
and triphenylphosphine (3.83 g, 14.6 mmol) in THF (200 mL)
at 0 °C was added slowly a THF (45 mL) solution of dimethyl
azodicarboxylate (DMAD) (3.56 g, 40% in toluene; 9.74 mmol)
during 3 h. After the addition, the mixture was stirred at room
temperature for 14 h and then concentrated in vacuo. The
residue was subjected to flash chromatography (15-50% ethyl
acetate in hexane). A fraction containing cyclization product
9 was collected and washed twice with water to remove 1,2-
dicarbomethoxyhydrazine. The solution was dried and con-
centrated in vacuo to give 2.12 g (90%) of 9: mp 138-139 °C
6,6′-Hep ta m eth ylen ed ioxy d er iva tive 13d : 1H NMR δ
1.25-1.9 (10H, m), 3.61 (2H, m), 3.72 (2H, br d, J ) ca. 11
Hz), 3.95-4.00 (2H, m), 4.05-4.15 (4H, m), 4.60 (4H, br s),
6.71 (2H, br d, J ) 8.1 Hz), 6.83 (2H, br d, J ) 8.1 Hz) 7.25-
7.35 (12H, m, including t (2H, J ) 8.1 Hz) at 7.27); 13C NMR
δ 24.48, 25.14, 26.59, 67.03, 70.71, 73.63, 85.13, 106.51, 113.57,
117.06, 127.61, 127.67, 128.37, 129.19, 138.06, 157.49, 159.78;
IR (KBr disk) 1100, 780, 740, 720, 695 cm-1; MS m/z (relative
intensity) 580 (M+, 42), 368 (95), 236 (100); HRMS calcd for
(recrystallized from EtOH); [R]30 +8.5 (c 1.20, CHCl3); 1H
D
NMR δ 3.60 (2H, ddd, J ) 2.4, 3.4, 10.9 Hz), 3.73 (2H, br, d,
J ) ca. 11 Hz), 4.19 (2H, m), 4.52 (2H, d, J ) 12.0 Hz), 4.58
(2H, d, J ) 12.0 Hz), 6.10 (2H, br s), 6.74 (2H, dd, J ) 1.0, 8.2
Hz), 6.83 (2H, dd, J ) 1.0, 8.2 Hz), 7.20 (2H, t, J ) 8.2 Hz),
7.27-7.37 (10H, m); 13C NMR (125.8 MHz) δ 70.21, 73.64,
84.89, 113.04, 114.70, 115.35, 127.77 (2C), 128.42, 129.99,
137.66, 153.29, 159.77; IR (KBr disk) 3180 (br), 1235, 1050,
790, 745, 695 cm-1; MS m/z (relative intensity) 484 (M+, 4),
287 (7), 91 (100); HRMS calcd for C30H28O6 484.1886, found
C
37H40O6 580.2825, found 580.2829.
6,6′-Deca m eth ylen ed ioxy d er iva tive 13e: mp 140-142
1
°C (recrystallized from ethyl acetate and hexane); H NMR δ
1.40 (8H, m), 1.64 (4H, m), 3.59 (2H, m), 3.71 (2H, m), 3.86
(4H, br t, J ) ca. 6.5 Hz), 4.10 (2H, m), 4.56 (4H, s), 6.75 (2H,
d, J ) 8.4 Hz), 6.82 (2H, d, J ) 7.9 Hz), 7.25 (2H, t, J ) 8.0
Hz), 7.3-7.35 (10H, m); 13C NMR δ 23.84, 25.57, 25.57, 27.79,
68.88, 70.75, 73.64, 85.08, 108.65, 114.07, 118.10, 127.61,
127.68, 128.37, 129.04, 138.08, 158.26, 159.62; IR (KBr disk)
1090, 785, 740, 700 cm-1; MS m/z (relative intensity) 622 (M+,
100), 425 (17); HRMS calcd for C40H46O6 622.3296, found
622.3289.
(27) Lindsten, G.; Wennerstorm, O.; Isaksson, R. J . Org. Chem.
1987, 52, 547.

Asymmetric Synthesis of Axially Chiral Biaryls
J . Org. Chem., Vol. 65, No. 5, 2000 1341
Gen er al P r ocedu r e for th e Syn th esis of (S)-2,2′-Biph en -
yld iols 14a -e. A mixture of 13a -e (1 mmol) and Pd/C (10%,
270 mg) in ethanol (100 mL) was vigorously stirred under H2
atmosphere at room temperature for 12-16 h. The mixture
was filtered through a pad of cellulose, and the filtrate was
concentrated in vacuo. To a DMSO (20 mL) solution of the
resulting oil at room temperature was added KN(TMS)2 (10
mL, 1 M in THF, 10 mmol). After being stirred at 50 °C for 7
h, the mixture was poured into 1 N aqueous HCl and extracted
twice with ethyl acetate. The dried organic layers were
concentrated in vacuo. Purification of the residue by flash
chromatography (30-50% ethyl acetate in hexane) gave (S)-
biphenyldiols 14a -c5c and 14d ,e.
The ee values of 14a ,d ,e and 14b,c were established by
HPLC analyses using Chiracel OD column and by 1H NMR
analysis of the mono-MTPA derivatives, respectively. Mono-
(R)-MTPA ester of 14b: 1H NMR δ 1.4-1.55 (2H, m), 1.6-
1.75 (4H, m), 3.28 (3H, br s), 3.52 (1H, br s), 4.0-4.1 (2H, m),
4.25-4.4 (2H, m), 6.52 (1H, dd, J ) 0.6, 8.1 Hz), 6.58 (1H, br
d, J ) ca. 8 Hz), 6.76 (1H, br d, J ) ca. 8 Hz), 6.99 (1H, br d,
J ) ca. 8 Hz), 7.17 (1H, t, J ) 8.1 Hz), 7.25-7.45 (6H, m) [a
minor diastereomer resonated at δ 3.30 (3H, br s) and 6.82
(1H, br d, J ) ca. 8 Hz)]. Mono-(R)-MTPA ester of 14c: 1H
NMR δ 1.3-1.4 (4H, m), 1.5-1.7 (4H, m), 3.20 (3H, br s), 3.9-
4.0 (1H, m), 4.0-4.25 (3H, m), 4.91 (1H, br s), 6.53 (1H, br d,
J ) ca. 8 Hz), 6.56 (1H, br d, J ) ca. 8 Hz), 6.72 (1H, br d,
J ) ca. 8 Hz), 6.96 (1H, br d, J ) ca. 8 Hz), 7.17 (1H, t, J ) 8.1
Hz), 7.3-7.4 (5H, m), 7.40 (1H, t, J ) 8.1 Hz) [a minor di-
astereomer resonated at δ 3.27 (3H, br s) and 4.81 (1H, br s)].
(S)-6,6′-Heptam eth yledioxy-2,2′-biph en yldiol (14d): mp
221-222 °C (recrystallized from benzene); [R]33D +89.0 (c 0.78,
EtOH); 1H NMR δ 1.2-1.4 (4H, m), 1.4-1.6 (2H, m), 1.6-1.85
(4H, m), 3.95-4.05 (2H, m), 4.05-4.15 (2H, m), 5.00 (2H, br
s), 6.53 (2H, br d, J ) 8.1 Hz), 6.64 (2H, br d, J ) 8.1 Hz),
7.24 (2H, t, J ) 8.1 Hz); 13C NMR δ 25.04, 25.24, 26.29, 67.51,
104.10, 106.80, 108.01, 130.32, 154.92, 157.91; IR (KBr disk)
3420 (br), 1190, 780, 735 cm-1; MS m/z (relative intensity) 314
(M+, 100), 218 (86), 200 (31); HRMS calcd for C19H22O4
314.1516, found 314.1517. Anal. Calcd for C19H22O4: C, 72.59;
H, 7.05. Found: C, 72.56; H, 7.12.
under similar conditions. To a suspension of 17 (1.0 mmol)
and PdCl2(dppf) (0.05 mmol) in THF (20 mL) at 0 °C was added
a THF solution of RZnCl (4.0 mmol). For the reaction with
MeZnCl, the solution was treated with DIBALH (0.10 mL, 1
M in hexane, 0.10 mmol) at 0 °C for 10 min before the addition
of MeZnCl. After being stirred at 65 °C for 20-37 h, the
resulting mixture was diluted with ether, poured into aqueous
NH4Cl, and extracted twice with ether. The organic layers were
washed with aqueous NaHCO3, dried, and concentrated in
vacuo. Purification of the residue by flash chromatography
(2-30% ethyl acetate in hexane) gave dialkylation products
18a -d .
6,6′-Dim eth yl d er iva tive 18a : mp 101-102 °C (recrystal-
lized from ethyl acetate and hexane); 1H NMR δ 2.17 (6H, s),
3.59 (2H, br d, J ) ca. 10 Hz), 3.70 (2H, br d, J ) ca. 10 Hz),
4.11 (2H, m), 4.57 (4H, br s), 7.06 (4H, d, J ) 7.8 Hz), 7.25
(2H, t, J ) 7.8 Hz), 7.3-7.4 (10H, m); 13C NMR δ 19.72, 70.65,
73.55, 85.65, 119.08, 125.90, 127.63, 127.63, 128.32, 128.61,
130.21, 137.61, 137.94, 159.14; IR (KBr disk) 1095, 790, 760,
740, 700 cm-1; MS m/z (relative intensity) 480 (M+, 45), 389
(13), 91 (100); HRMS calcd for C32H32O4 480.2302, found
480.2305.
1
6,6′-Dieth yl d er iva tive 18b: H NMR δ 1.03 (6H, t, J )
7.5 Hz), 2.2-2.6 (4H, m), 3.63 (2H, br d, J ) ca. 11 Hz), 3.71
(2H, br d, J ) ca. 11 Hz), 4.11 (2H, m), 4.58 (4H, br s), 7.09
(2H, br d, J ) 7.5 Hz), 7.13 (2H, br d, J ) 7.5 Hz), 7.3-7.4
(12H, m); 13C NMR δ 15.01, 26.13, 70.72, 73.50, 85.69, 119.19,
123.79, 127.56, 127.64, 128.30, 128.86, 129.41, 138.03, 143.49,
159.24; IR (KBr disk) 1090, 755, 735, 695 cm-1; MS m/z
(relative intensity) 508 (M+, 66), 311 (34), 91 (100); HRMS
calcd for C34H36O4 508.2615, found 508.2609.
1
6,6′-Dibu tyl d er iva tive 18c: H NMR δ 0.73 (6H, t, J )
7.2 Hz), 1.13 (4H, sextet, J ) 7.2 Hz), 1.25-1.5 (4H, m), 2.4-
2.6 (4H, m), 3.64 (2H, br d, J ) ca. 11 Hz), 3.71 (2H, br d, J )
ca. 11 Hz), 4.11 (2H, m), 4.59 (4H, br s), 7.07 (2H, br d, J )
7.5 Hz), 7.09 (2H, br d, J ) 7.5 Hz), 7.25-7.34 (12H, m); 13C
NMR δ 13.67, 22.17, 32.81, 33.16, 70.72, 73.48, 85.64, 119.12,
124.46, 127.57, 127.66, 128.33, 128.67, 129.84, 138.10, 142.26,
159.27; IR (neat film) 1100, 765, 735, 700 cm-1; MS m/z
(relative intensity) 564 (M+, 34), 367 (28), 91 (100); HRMS
calcd for C38H44O4 564.3241, found 564.3243.
(S)-6,6′-Decam eth ylen edioxy-2,2′-biph en yldiol (14e): mp
1
131-132 °C (recrystallized from benzene); [R]32D -165 (c 0.56,
6,6′-Dip h en yl d er iva tive 18d : H NMR δ 3.72 (2H, br d,
1
EtOH); H NMR δ 1.0-1.35 (12H, m), 1.5-1.6 (4H, m), 3.9-
J ) ca. 11 Hz), 3.80 (2H, br d, J ) ca. 11 Hz), 4.29 (2H, m),
4.65 (4H, br s), 6.44 (4H, br d, J ) ca. 7 Hz), 6.9-7.0 (6H, m),
7.05 (2H, br t, J ) ca. 7 Hz), 7.25-7.40 (14 H, m); 13C NMR δ
70.69, 73.66, 85.58, 120.75, 125.84, 126.06, 127.21, 127.71,
127.74, 128.73, 129.14, 137.97, 140.54, 142.67, 159.94; IR (neat
film) 1900, 735, 695 cm-1; MS m/z (relative intensity) 604 (M+,
74), 407 (22), 91 (100); HRMS calcd for C42H36O4 604.2613,
found 604.2617.
4.15 (4H, m), 5.38 (2H, br s), 6.64 (2H, br d, J ) 8.1 Hz), 6.72
(4H, d, J ) 8.1 Hz), 7.26 (2H, t, J ) 8.1 Hz); 13C NMR (125.8
MHz) δ 24.27, 25.71, 26.65, 27.73, 68.26, 105.78, 109.16,
109.96, 130.02, 155.63, 156.54; IR 3470 (br), 1190, 1080, 780,
725 cm-1; MS m/z (relative intensity) 356 (M+, 100), 218 (90),
200 (34); HRMS calcd for C22H28O4 356.1988, found 356.1986.
Anal. Calcd for C22H28O4: C, 74.13; H, 7.92. Found: C, 73.94;
H, 7.842.
Mon om eth yla tion p r od u ct 19a : 1H NMR δ 2.23 (3H, s),
3.6-3.8 (4H, m), 4.1-4.2 (2H, m), 4.56 (4H, br s), 7.05-7.1
(2H, m), 7.18 (1H, d, J ) 8.4 Hz), 7.25-7.45 (13H, m); MS m/z
(relative intensity) 614 (M+, 20), 523 (22), 91 (100); HRMS
calcd for C32H29O7F3S 614.1586, found 614.1581.
(S)-Bis(tr ifla te) 17. Trifluoromethanesulfonic anhydride
(1.1 mL, 6.6 mmol) was added to a solution of 6 (1.06 g, 2.19
mmol) in pyridine (4.4 mL) at 0 °C. After being stirred at room
temperature for 10 h, the reaction mixture was diluted with
ether, poured into 1 N aqueous HCl, and extracted twice with
ether. The dried organic layers were concentrated in vacuo.
Purification of the residue by flash chromatography (30% ethyl
acetate in hexane) gave 1.48 g (90%) of 17: [R]33D +17.9 (c 1.23,
EtOH); 1H NMR δ 3.65 (2H, br d, J ) ca. 11 Hz), 3.73 (2H, br
d, J ) ca. 11 Hz), 4.16 (2H, m), 4.58 (4H, br s), 7.25 (2H, dd,
J ) 0.9, 8.4 Hz), 7.28-7.38 (12H, m), 7.51 (2H, t, J ) 8.4 Hz);
13C NMR δ 69.90, 73.64, 85.84, 117.59, 118.31, (q, J ) 321
Hz), 120.19, 122.56, 127.71, 127.83, 128.46, 131.26, 137.66,
146.90, 160.38; IR (neat film) 795, 750, 695 cm-1; MS m/z
(relative intensity) 748 (M+, 1), 657 (37), 551 (39), 91 (100);
HRMS calcd for C32H26O10F6S2 748.0871, found 748.0870.
Gen er a l P r oced u r e for P a lla d iu m -Ca ta lyzed Cr oss-
Cou p lin g of Bis(tr ifla te) 17 w ith Or ga n ozin c Rea gen ts.
A solution of RZnCl (R ) Me, Bu, Ph) was prepared by
treatment of a THF (8 mL) solution of ZnCl2 (4.0 mmol) with
RLi (4.0 mmol) (MeLi; 1 M in ether, BuLi; 1.6 M in hexane,
PhLi; 1 M in cyclohexanes-ether) at 0 °C for 15 min. A solution
of EtZnCl was prepared by treatment of a THF (8 mL) solution
of ZnCl2 (2.0 mmol) with Et2Zn (2.0 mmol) (1 M in hexane)
Mon oet h yla t ion p r od u ct 19b : 1H NMR δ 1.10 (2H, t,
J ) 7.5 Hz), 2.45 (1H, dq J ) 7.5 and 15.0 Hz), 2.64 (1H, dt,
J ) 7.5 and 15.0 Hz), 3.6-3.8 (4H, m), 4.05-4.2 (2H, m), 4.56
(2H, br s), 4.57 (2H, br s), 7.06 (1H, br d, J ) ca. 8 Hz), 7.15-
7.2 (2H, m), 7.25-7.45 (13H, m); MS m/z (relative intensity)
628 (M+, 14), 503 (49), 91 (100); HRMS calcd for C33H31O7F3S
628.1742, found 628.1729.
Gen er al P r ocedu r e for th e Syn th esis of (S)-2,2′-Biph en -
yld iols 20a -d . To a solution of 17a -d (1.0 mmol) in CH2Cl2
(10 mL) at 0 °C was added BBr3 (1.7 mL, 18.0 mmol). After
being stirred for 8-10 h at room temperature, the reaction
mixture was diluted with CH2Cl2, poured into ice, and ex-
tracted twice with ether. The dried organic layers were
concentrated in vacuo. Purification of the residue by flash
chromatography (5-30% ethyl acetate in hexane) gave 20a 24
and 20b-d . Their ee values were established by HPLC
analyses using Chiracel OD column.
(S)-6,6′-Dieth yl-2,2′-bip h en yld iol (20b): mp 93-95 °C
(recrystallized from hexane); [R]35 -55.3° (c 1.03, EtOH); 1H
D
NMR δ 1.06 (6H, t, J ) 7.5 Hz), 2.29 (4H, q, J ) 7.5 Hz), 4.72

1342 J . Org. Chem., Vol. 65, No. 5, 2000
Tuyet et al.
(2H, br s), 6.90 (2H, d, J ) 8.1 Hz), 6.97 (2H, d, J ) 7.5 Hz),
7.31 (2H, t, J ) 7.8 Hz); 13C NMR δ 14.52, 26.08, 113.09,
118.83, 120.66, 130.19, 145.01, 153.84; IR (KBr disk) 3400 (br),
800, 750 cm-1; MS m/z (relative intensity) 242 (M+, 68), 213
(100); HRMS calcd for C16H18O2 242.1307, found 242.1316.
Anal. Calcd for C16H18O2: C, 79.30; H, 7.49. Found: C, 79.30;
H, 7.37.
yield. 23: mp 240-241 °C (recrystallized from ethyl acetate
and hexane); [R]25D +97.9 (c 0.515, CHCl3); 1H NMR (500 MHz)
δ 3.62 (2H, br d, J ) ca. 11 Hz), 3.69 (2H, br d, J ) ca. 11 Hz),
4.17 (2H, m), 4.57 (4H, br s), 7.3-7.35 (10H, m), 7.45 (4H, m),
7.94 (2H, m), 12.6 (2H, br); 13C NMR (125.8 MHz) δ 70.41,
73.72, 85.72, 127.03, 127.06, 127.67, 127.75, 128.43, 129.17,
130.26, 130.67, 137.79, 158.68, 172.44; FT-IR (KBr disk) 3450
(br), 1697, 729, 767, 698 cm-1; MS m/z (relative intensity) 540
(M+, <1), 431 (46), 91 (100); HRMS calcd for C32H28O8
540.1784, found 540.1801. Anal. Calcd for C32H28O8: C, 71.10;
H, 5.22. Found: C, 71.18; H, 5.49. 24: 1H NMR (500 MHz) δ
3.63 (2H, m), 3.71 (2H, br d, J ) ca. 10 Hz), 4.15 (2H, br s),
4.58 (4H, br s), 6.06 (2H, br s), 6.76 (1H, br s), 7.30-7.38 (15H,
m), 7.73 (1H, br t, J ) ca. 4.5 Hz); 13C NMR (125.8 MHz) δ
70.41, 70.41, 73.69, 73.69, 85.27, 85.62, 123.75, 124.50, 126.20,
126.75, 127.71, 128.22, 128.43, 129.51, 129.53, 129.68, 136.55,
137.79, 137.82, 158.39, 158.66, 170.88, 172.31; FT-IR (KBr
disk) 3490 (br), 3390 (br), 3205 (br), 1709, 1651, 768, 735, 698
cm-1; MS m/z (relative intensity) 521 (M+ - H2O, 20), 430 (31),
91 (100); HRMS calcd for C32H27NO6 (M+ - H2O) 521.1839,
found 521.1829.
(S)-6,6′-Dibu tyl-2,2′-bip h en yld iol (20c): mp 48-49 °C
1
(recrystallized from hexane) [R]22 -28.3 (c 1.13, EtOH); H
D
NMR δ 0.77 (6H, t, J ) 7.2 Hz), 1.15-1.25 (4H, m), 1.41 (4H,
quintet, J ) 7.2 Hz), 2.2-2.3 (4H, m), 4.73 (2H, s), 6.88 (2H,
d, J ) 7.5 Hz), 6.94 (2H, d, J ) 8.2 Hz), 7.28 (2H, t, J ) 7.8
Hz); 13C NMR δ 13.71, 22.51, 32.34, 32.75, 113.00, 118.85,
121.42, 130.09, 143.76, 153.83; FT-IR (KBr disk) 3490 (br),
3420 (br), 796, 741 cm-1; MS m/z (relative intensity) 298 (M+,
68), 241 (100); HRMS calcd for C20H26O2 298.1933, found
298.1913. Anal. Calcd for C20H26O2: C, 80.50; H, 8.78. Found:
C, 80.10; H, 8.87.
(S)-1,1′:2′,1′′:2′′,1′′′-Qu a ter p h en yl-3′,6′′-d iol (20d ): mp
135-136 °C (recrystallized from benzene); [R]25D -86.3 (c 1.02,
1
CHCl3); H NMR (500 MHz) δ 5.27 (2H, br s), 6.67 (4H, br d,
J ) ca.8 Hz), 6.86 (2H, dd, J ) 0.9, 7.6 Hz), 7.04 (1H, dd, J )
0.9, 8.2 Hz), 7.08 (4H, br t, J ) ca. 8 Hz), 7.16 (2H, br t, J )
ca. 8 Hz), 7.33 (2H, br t, J ) ca. 8 Hz); 13C NMR δ 114.39.
119.33, 122.76, 126.57, 127.29, 128.69, 130.05, 140.04, 144.01,
154.30; IR (KBr disk) 3580, 3400 (br), 755, 700 cm-1; MS m/z
(relative intensity) 338 (M+, 100), 281 (18); HRMS calcd for
La cton e 26. Monocyano derivative 22 (0.14 g, 0.22 mmol)
was treated with KOH (0.89 g, 15 mmol) in water (0.5 mL)
and 2-ethoxyethanol (0.8 mL) first at room temperature for 1
h and then at 138 °C for 10 h. The resulting mixture was
poured into 1 N aqueous HCl and extracted three times with
ethyl acetate. The organic layers were dried and concentrated
in vacuo. The reside was dissolved in toluene (3 mL) containing
p-toluenesulfonic acid monohydrate and heated at 50 °C for 4
h. The reaction mixture was poured into water and extracted
three times with ethyl acetate. The dried organic layers were
concentrated in vacuo. Purification of the residue by flash
chromatography (3-5% ethyl acetate in benzene) gave 86 mg
(80%) of 26: mp 124-124.5 °C (recrystallized from EtOH);
C
24H18O2 338.1307, found 338.1308.
6,6′-Dicya n o Der iva tive 21 (Ta ble 4, En tr y 3). A mixture
of bis(triflate) 17 (0.15 g, 0.19 mmol), Zn(CN)2 (47 mg, 0.40
mmol), and Pd(PPh3)4 (23 mg, 0.02 mmol) in DMF (0.2 mL)
was stirred at 150 °C for 16 h. The resulting mixture was
diluted with ethyl acetate, poured into aqueous NaHCO3, and
extracted three times with ethyl acetate. The dried organic
layers were concentrated in vacuo. The residue was purified
by flash chromatography (15-40% ethyl acetate in hexane)
to give 84 mg (86%) of 21: 1H NMR (500 MHz) δ 3.60 (2H, br
td, J ) ca. 1.5, 10.2 Hz), 3.75 (2H, br d, J ) 10.2 Hz), 4.17
(2H, m), 4.55 (2H, d, J ) 12.1 Hz), 4.62 (2H, d, J ) 12.1 Hz),
7.3-7.4 (10H, m), 7.50 (2H, dd, J ) 1.0, 8.1 Hz), 7.57 (2H, t,
J ) 8.0 Hz), 7.65 (2H, dd, J ) 1.0, 7.5 Hz); 13C NMR (125.8
MHz) δ 69.69, 73.74, 85.39, 113.91, 117.38, 127.44, 127.73,
127.94, 128.50, 129.55, 131.25, 131.48, 137.39, 159.03; IR (KBr
disk) 2240, 805, 740, 700 cm-1; MS m/z (relative intensity) 502
(M+, 2), 411 (62), 305 (42), 91 (100); HRMS calcd for C32H26N2O4
502.1892, found 502.1884.
[R]23 -55.0 (c 0.695, CHCl3); 1H NMR (500 MHz) δ 3.69 (2H,
D
br s), 3.80 (2H, br s), 4.48 (2H, br), 4.55 (2H, br d, J ) ca. 11
Hz), 4.64 (2H, br d, J ) ca. 11 Hz), 7.13 (1H, br d, J ) ca. 8
Hz), 7.15 (1H, br d, J ) ca. 8 Hz), 7.3-7.4 (11H, m), 7.51 (1H,
br t, ca. 8 Hz), 7.61 (1H, br d, ca. 8 Hz), 8.18 (1H, br d, J ) ca.
8 Hz); 13C NMR (125.8 MHz) δ 73.51, 123.56, 127.75, 127.86,
128.27, 128.43, 129.39, 129.98, 137.46, 151.27, 160.88 (other
resonances were too broad to be observed); FT-IR (KBr disk)
1728, 735, 696 cm-1; MS m/z (relative intensity) 494 (M+, 30),
297 (20), 91 (100); HRMS calcd for C31H26O6 494.1729, found
494.1725. Anal. Calcd for C31H26O6: C, 75.29; H, 5.30. Found:
C, 74.95; H, 5.36.
Mon ocya n o Der iva tive 22 (Ta ble 4, En tr y 4). A mixture
of bis(triflate) 17 (0.45 g, 0.60 mmol), Zn(CN)2 (0.14 g, 1.2
mmol), and Pd(PPh3)4 (23 mg, 0.02 mmol) in DMF (0.5 mL)
was stirred at 120 °C for 3 h. Aqueous workup similar to that
described above and purification of the crude products by flash
chromatography (10-30% ethyl acetate in hexane) gave, in
the order of elution, 17 (171 mg, 38%), 22 (165 mg, 44%), and
21 (54 mg, 18%). 22: 1H NMR (500 MHz) δ 3.6-3.7 (2H, m),
3.75 (1H, br d, J ) ca. 10 Hz), 3.82 (1H, br d, J ) ca. 10 Hz),
4.22 (2H, br s), 4.59 (1H, d, J ) 12.1 Hz), 4.61 (2H, br s), 4.67
(1H, d, J ) 12.1 Hz), 7.3-7.45 (12H, m), 7.55-7.65 (4H, m);
13C NMR (125.8 MHz) δ 69.70 (2C), 73.57, 73.62, 85.49, 85.58,
113.99, 117.31, 118.22, 118.23 (q, J ) 329.9 Hz), 122.59,
122.63, 125.74, 127.55, 127.67, 127.80, 127.85, 128.24, 128.41,
6-Cya n o-6′-p h en yl Der iva tive 27. Cross coupling of 22
with PhZnCl was carried out according to a procedure similar
to that described for 17. Purification of the crude products by
flash chromatography (5% ethyl acetate in benzene) gave 27
in 95% yield: 1H NMR (500 MHz) δ 3.66 (1H, br d, J ) ca. 11
Hz), 3.70 (1H, br d, J ) ca. 11 Hz), 3.80 (2H, br d, J ) ca. 11
Hz), 3.82 (2H, br d, J ) ca. 11 Hz), 4.25 (2H, m), 4.59 (1H, d,
J ) 12.1 Hz), 4.54 (2H, br s), 4.56 (1H, d, J ) 12.1 Hz), 7.21
(1H, dd, J ) 1.0, 7.6 Hz), 7.24 (4H, m), 7.28 (1H, dd, J ) 1.0,
7.6 Hz), 7.35-7.45 (8H, m), 7.50 (1H, dd, J ) 1.0, 7.6 Hz), 7.53
(1H, t, J ) 7.6 Hz); 13C NMR (125.8 MHz) δ 70.02, 70.26, 73.63,
73.63, 85.17, 85.76, 114.23, 117.63, 120.97, 126.19, 126.85,
126.90, 127.65, 127.70, 127.77, 127.80, 128.41, 128.86, 129.55,
130.36, 130.74, 134.62, 137.61, 137.63, 139.87, 143.14, 159.08,
159.69; IR (KBr disk) 2220, 760, 730, 695 cm-1; MS m/z
(relative intensity) 553 (M+ 32), 462 (14), 91 (100); HRMS calcd
for C37H31NO4 553.2253, found 553.2263.
128.43, 128.88, 131.24, 131.40, 137.43, 137.53, 146.64, 159.50,
-1
159.89; IR (KBr disk) 2230, 1220, 1140, 800, 735 cm
;
MS m/z (relative intensity) 625 (M+, 1), 534 (58), 428 (32),
91 (100); HRMS calcd for C32H26NO7F3S 625.1382, found
625.1382.
Ter p h en yl Ca r boxylic Acid 28. The acid was obtained
in 55% yield by hydrolysis of 27 by a procedure similar to that
Dica r boxylic Acid 23. Dicyano derivative 21 (0.26 g, 0.52
mmol) was treated with KOH (1.02 g, 18.17 mmol) in water
(0.5 mL) and 2-ethoxyethanol (0.8 mL) at 138 °C for 10 h. The
resulting mixture was diluted with water, poured into 1 N
aqueous HCl, and extracted three times with ethyl acetate.
The organic layers were dried and concentrated in vacuo. The
residue was purified by chromatography (40-70% ethyl ac-
etate in hexane) to give, in the order of elution, dicarboxylic
acid 23 (131 mg, 47%) and amidocarboxylic acid 24 (109 mg,
38%). Hydrolysis of 24 under similar conditions gave 23 in 72%
described for the preparation of diacid 23. 28: [R]25 -72.8 (c
D
0.86, CHCl3); 1H NMR (500 MHz) δ 3.65-3.75 (2H, m), 3.75-
3.8 (2H, m), 4.2-4.3 (2H, m), 4.61 (2H, br s), 4.64 (2H, br s),
6.2 (1H, br), 6.96 (2H, br d, J ) ca. 7 Hz), 7.13 (1H, br s, J )
ca. 7 Hz), 7.15 (1H, br d, J ) ca. 7 Hz), 7.18 (2H, br t, J ) ca.
7 Hz), 7.25 (1H, br s, J ) ca. 7 Hz), 7.3-7.5 (14H, m); 13C NMR
(125.8 MHz) δ 70.39, 70.64, 73.72, 73.75, 85.10, 85.85, 120.92,
125.87, 126.02, 126.27, 126.64, 127.78, 127.80, 127.82, 128.47,
128.90, 129.66, 130.26, 131.34, 131.81, 137.88, 140.24, 142.84,
158.46, 159.73, 171.04; FT-IR (KBr disk) 3500 (br), 1693, 764,

Asymmetric Synthesis of Axially Chiral Biaryls
J . Org. Chem., Vol. 65, No. 5, 2000 1343
700 cm-1; MS m/z (relative intensity) 572 (M+, 50), 503 (7), 91
(100); HRMS calcd for C37H32O6 572.2199, found 572.2207.
Cyclic Am id in e Der iva tive 29. To a mixture of Pd(OAc)2
(6 mg, 0.03 mmol), BINAP (25 mg, 0.04 mmol), and Cs2CO3
(0.24 g, 0.75 mmol) at room temperature was added a toluene
(1 mL) solution of 22 (0.33 g, 0.53 mmol) and benzylamine (0.1
mL, 1.1 mmol). The mixture was stirred first at room tem-
perature for 0.5 h and then at 100 °C for 16 h. The reaction
mixture was diluted with ethyl acetate, poured into aqueous
NaHCO3, and extracted three times with ethyl acetate. The
dried organic layers were concentrated in vacuo. Purification
of the residue by flash chromatography (30-60% ethyl acetate
in hexane) gave 176 mg (57%) of 29: 1H NMR (500 MHz) δ
3.72 (2H, m), 3.87 (2H, br s), 4.49 (2H, m), 4.55-4.75 (4H, m),
4.9-5.05 (4H, m), 5.75 (1H, br s), 7.12 (1H, br d, J ) ca. 7.5
Hz), 7.3-7.4 (12H, m), 7.45-7.65 (8H, m); 13C NMR (125.8
MHz) δ 69.78, 73.59, 116.96, 121.75, 127.41, 127.62, 127.70,
127.74, 128.89, 128.43, 128.66, 128.83, 137.84, 139.14, 152.61
(other resonances were too broad to be observed); FT-IR (KBr
disk) 3400 (br), 1649, 1521, 1250, 723, 696 cm-1; MS m/z
(relative intensity) 582 (M+, 84), 360 (57), 91 (100); HRMS
calcd for C38H34N2O4 582.2518, found 582.2515.
the preparation of diacid 23. 30: mp 118-119 °C (recrystal-
lized from benzene and hexane); [R]24 -152 (c 0.87, CHCl3);
D
1H NMR (500 MHz) δ 3.73 (2H, br dd, J ) ca. 6, 11 Hz), 3.86
(2H, br δ J ) ca. 11 Hz), 4.47 (2H, br), 4.61 (2H, br d, J ) ca.
12 Hz), 4.68 (2H, br d, J ) ca. 12 Hz), 7.10 (1H, br d, J ) ca.
7.5 Hz), 7.21 (1H, br d, J ) ca. 7.5 Hz), 7.3-7.45 (11H, m),
7.58 (1H, br t, J ) ca. 7.5 Hz), 7.62 (1H, br t, J ) ca. 7 Hz),
8.36 (1H, br d, J ) ca. 7.5 Hz), 11.47 (1H, br s); 13C NMR (125.8
MHz) δ 69.6 (br), 73.58, 89.0 (br), 111.5 (br), 116.8 (br), 123.2
(br), 126.9 (br), 127.72, 127.77, 128.43, 129.69, 136.98, 137.69,
126.0 (br), 157.1 (br), 163.05, 171.14 (other resonances were
too broad to be observed); FT-IR (KBr disk) 3185 (br), 1664,
738, 698 cm-1; MS m/z (relative intensity) 493 (M+, 71), 296
(10), 91 (100); HRMS calcd for C31H27NO5 493.1889, found
493.1880. Anal. Calcd for C31H27NO5: C, 75.44; H, 5.51; N,
2.84. Found: C, 75.26; H, 5.65; N, 2.77.
Su p p or tin g In for m a tion Ava ila ble: X-ray crystallo-
1
graphic data for 18a and H NMR spectra of compounds 5-7,
13a -e, 17, 18a -d , 19a ,b, 20d ,e, 21, 22, 24, and 27-29. This
material is available free of charge via the Internet at
http://pubs.acs.org.
La cta m 30. The compound was obtained in 67% yield by
hydrolysis of 29 by a procedure similar to that described for
J O991364G