Facile preparation of optically pure 7,7′-disubstituted BINOLS and their application in asymmetric catalysis

Article abstract of DOI:10.1021/jo034831+

A family of optically pure 7,7′-disubsituted-2,2′ -dihydroxy-1,1′-dinaphthyls have been conveniently prepared from easily accessible 7-alloxyl-2-naphthol by reaction sequences beginning with the asymmetric oxidative coupling and followed by key synthetic steps including deprotection, alkylation, and Suzuki coupling. Application of these binaphthols in catalytic phenylacetylene addition to aldehydes resulted in excellent enantioselectivities.

Full text of DOI:10.1021/jo034831+

changing the substituent size. Thus, a convenient method
to easily approach 7,7′-disubsituted binaphthol is of great
interest for asymmetric catalysis and organic material.
However, reports on the syntheses of optically pure 7,7′-
disubstituted binaphthols are scarce due to their syn-
thetic challenges.5 Here we will report a practical method
for preparing optically pure 7,7′-disubstituted binaph-
thols based on our chiral oxovanadium complex 1 cata-
lyzed asymmetric oxidative coupling of 2-naphthols.6 The
application of these 7,7′-disubstituted binaphthols in
phenylacetylene additon to aldehydes will also be pre-
sented.
F a cile P r ep a r a tion of Op tica lly P u r e
7,7′-Disu bstitu ted BINOLs a n d Th eir
Ap p lica tion in Asym m etr ic Ca ta lysis
Quan-Zhong Liu,†,‡ Nan-Sheng Xie,‡ Zhi-Bin Luo,†
Xin Cui,† Lin-Feng Cun,† Liu-Zhu Gong,*,†
Ai-Qiao Mi,† and Yao-Zhong J iang*,†
Key Laboratory for Asymmetric Synthesis and
Chirotechnology of Sichuan Province, Chengdu Institute of
Organic Chemistry, Chinese Academy of Sciences,
Chengdu, 610041, China, and Chemistry Department,
Sichuan Teachers College, Nanchong, 637002, China
P r ep a r a tion of 7,7′-d isu bstitu ted bin a p h th ols: In
the presence of 5 mol % of catalyst 1 that was developed
in our laboratory,6 the asymmetric oxidative coupling of
7-alloxyl-2-naphthol (2) in 5.0-g scale gave chiral 7,7′-
dialloxyl-2,2′-dihydroxy-1,1′-dinaphthyl (3) in nearly quan-
titive yield with 95% ee, without loss of the enantiose-
lectivity with respect to the small scale. After recrystal-
lization, optically pure 3, which is an important chiral
starting material for the following synthesis, was ob-
tained in 95% yield.6 The treatment of optically pure 3
with methoxymethyl chloride (MOMCl) in the presence
of excess sodium hydride (NaH) gave compound 4. After
removal of allyl groups from compound 4 by a palladium-
catalyzed deprotection strategy,7 the optically pure key
synthetic intermediate 5 was provided in 90% yield
(Scheme 1).
Alkylations of 5 with alkylbromides in the presence of
a stoichiometric amount of CsOH in DMF at room
temperature smoothly furnished compounds 6. Without
further purification, compounds 6 were directly subjected
to hydrolysis with 6 N HCl in a solvent mixture of
chloroform and ethanol at 65 °C, providing 7,7′-dialkoxyl-
2,2′-dihydroxy-1,1′-dinaphthyl (7) in high yields ranging
from 85% to 93% (2 steps) (Scheme 2).
gonglz@cioc.ac.cn
Received J une 16, 2003
Abstr a ct: A family of optically pure 7,7′-disubsituted-2,2′-
dihydroxy-1,1′-dinaphthyls have been conveniently prepared
from easily accessible 7-alloxyl-2-naphthol by reaction se-
quences beginning with the asymmetric oxidative coupling
and followed by key synthetic steps including deprotection,
alkylation, and Suzuki coupling. Application of these bi-
naphthols in catalytic phenylacetylene addition to aldehydes
resulted in excellent enantioselectivities.
Optically pure 1,1′-binaphthol and its derivatives have
been proven to be versatile chiral auxiliaries and ligands
in a great number of asymmetric transformations with
exciting stereoselectivities. Research on this area has
provided many efficient and useful methods for the
preparation of key chiral building blocks, some of which
have been used for the construction of complex natural
products.1 In addition, some chiral organic materials have
been prepared starting with them.2 Subtle variation of
dihedral angle or electrical densities of binaphthols and
their analogues generally leads to the improvement of
catalytic performance of the ligand.3 Functionalization
of BINOL at its 3,6-positions has furnished many efficient
chiral ligands that have been used in numerous success-
ful asymmetric transformations.2a,4 Compared with the
3,6-substituted binaphthols, 7,7′-disubsituted binaph-
thols have much more easily tunable dihedral angles by
Optically pure cyclo-disubsituted binaphthols (8 and
9) at 7,7′-positions linked by alkyl or crown ether were
also furnished by reactions of 5 with alkyl dibromides or
(4) (a) Lee, S. J .; Hu, A.; Lin W. J . Am. Chem. Soc. 2002, 124, 12948.
(b) Long, J .; Hu, J .; Shen, X.; J i, B.; Ding, K. J . Am. Chem. Soc. 2002,
124, 10. (c) Yamashita, Y.; Saito, S.; Ishitani, H.; Kobayashi, S. J . Am.
Chem. Soc. 2003, 125, 3793 and references therein.
(5) For asymmetric synthesis from the chiral pool: (a) Lipshutz, B.
H.; Shin, Y. J . Tetrahedron Lett. 2000, 41, 9515. (b) Lipshutz, B. H.;
Shin, Y. J . Tetrahedron Lett. 1998, 39, 7017. For asymmetric catalytic
coupling of 7-subsituted naphthols, see: (c) Mulrooney, C. A.; Li, X.;
DiVirgilio, E. S.; Kozlowski, M. C. J . Am. Chem. Soc. 2003, 125, 6856.
(d) Chu, C. Y.; Hwang, D. R.; Wang, S. K.; Uang, B. J . Chem. Commun.
2001, 980. (e) Hon, S. W.; Li, C. H.; Kuo, J . H.; Barhate, N. B.; Liu, Y.
H.; Wang, Y.; Chen, C. T. Org. Lett. 2001, 3, 869. (f) Luo, Z.; Liu, Q.;
Gong, L.; Mi, A.; Cui, X.; J iang, Y. Chem. Commun. 2002, 914. (g)
Nakajima, M.; Miyoshi, I.; Kanayama, K.; Hashimoto, S.-i. J . Org.
Chem. 1999, 64, 2264. (h) Li, X.; Yang, J .; Kozlowski, M. C. Org. Lett.
2001, 3, 1137. For resolution see: (i) Bandin, M.; Casolari, S.; Cozzi,
P. G.; Proni, G.; Schmohel, E.; Spada, G. P.; Tagliavini, E.; Umani-
Ronchi, A. Eur. J . Org. Chem. 2000, 491. (j) Reeder, J .; Castro, P. P.;
Knobler, C. B.; Martinborough, E.; Owens, L.; Diederich, F. J . Org.
Chem. 1994, 59, 3151.
(6) Luo, Z.; Liu, Q.; Gong, L.; Mi, A.; Cui, X.; J iang, Y. Angew. Chem.,
Int. Ed. 2002, 41, 4532.
(7) (a) Beugelmans, R.; Bourdet, S.; Bigot, A.; Zhu, J . Tetrahedron
Lett. 1994, 35, 4349. (b) Smith, A. B., III; Rivero, R. A.; Hale, K. J .;
Vaccaro, H. A. J . Am. Chem. Soc. 1991, 113, 2092. (c) Vutukuri, D. R.;
Bharathi, P.; Yu, Z.; Rajasekaran, K.; Tran, M.-H.; Thayumanavan,
S. J . Org. Chem. 2003, 68, 1146.
† Chengdu Institute of Organic Chemistry.
‡ Sichuan Teachers College.
(1) For reviews, see: (a) Noyori, R. Asymmetric Catalysis in Organic
Synthesis; Wiley: New York, 1994. (b) Noyori, R.; Takaya, H. Acc.
Chem. Res. 1990, 23, 345. (c) Comprehensive Asymmetric Catalysis;
J acobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin,
Germany, 1999. (d) J orgensen, K. A. Angew. Chem., Int. Ed. 2000, 39,
3558. (e) Bolm, C.; Hildebrand, J . P.; Muniz, K.; Hermanns, N. Angew.
Chem., Int. Ed. 2001, 40, 3284.
(2) For reviews, see: (a) Pu, L. Chem. Rev. 1998, 98, 2405. For
leading representative research, see: (b) Irie, M.; Yorozu, T.; Hayashi,
K. J . Am. Chem. Soc. 1978, 100, 2236. (c) J ames, T. D.; Sandanayke,
K. R. A. S.; Shinkai, S. Nature 1995, 374, 345. (d) Akagi, K.; Piao, G.;
Kaneko, S.; Sakamaki, K.; Shirakawa, H.; Kyotani, M. Sciences 1998
282, 1683. (e) Zheng, L.; Urian, R. C.; Liu, Y.; J en, A. K. Y.; Pu, L.
Chem. Mater. 2000, 12, 13. (f) Pugh, V. J .; Hu, Q. S.; Pu, L Angew.
Chem., Int. Ed. 2000, 39, 3638. (g) Gong, L. Z.; Hu, Q. S.; Pu, L. J .
Org. Chem. 2001, 66, 2358. (h) Lin, J .; Hu, Q. S.; Xu, M. H.; Pu, L. J .
Am. Chem. Soc. 2002, 124, 2088. (i) Cui, Y.; Evans, O. R.; Ngo, H. L.;
White, P. S.; Lin, W. B. Angew. Chem., Int. Ed. 2002, 41, 1159.
(3) Zhang, Z.; Qian, H.; Longmire, J .; Zhang, X. J . Org. Chem. 2000,
65, 6223 and the references therein.
10.1021/jo034831+ CCC: $25.00 © 2003 American Chemical Society
Published on Web 09/10/2003
J . Org. Chem. 2003, 68, 7921-7924
7921

SCHEME 3. Th e P r ep a r a tion of Op tica lly P u r e
Cyclo-Disu bsitu ted Bin a p h th ols 8 a n d 9a
F IGURE 1. The catalyst used for this study.
SCHEME 1. P r ep a r a tion of Com p ou n d 5a
a
Reaction conditions: (a) CsOH, DMF, rt, 2 h; (b) aqueous HCl,
CHCl3/EtOH, 65 °C, 2 h. (c) CsOH, DMF, 80 °C, 5 h.
To determine the absolute configuration of the binaph-
thols, a dehydroxylation of 10 was performed in the
presence of 1 mol % of Pd(PPh3)4 with HCO2H as the
i
hydrogen source and Pr2NEt as the base to give (R)-
BINOL (Scheme 5).9 Therefore the 7,7′-disubstituted
binaphthols (3, 7-9, and 11) were assigned to the (R)-
configuration.
a
Reaction conditions: (a) 5 mol % of 1, O2, CCl4, 0 °C, 99% yield,
En a n tioselective p h en yla cetylen e a d d ition to a l-
d eh yd es ca ta lyzed by Ti(IV) com p lexes of 7,7′-
d isu bstitu ted bin a p h th ols: These chiral 7,7-disubsti-
tuted BINOLs 7-9 and 11, in combination with Ti(OiPr)4,
were then surveyed to catalyze enantioselective phenyl-
acetylene addition to aldehydes under the reported
optimal conditions.10 The results were summarized in
Table 1.
95% ee; (b) recrystallization (solvent: EtOAc/PE ) 1/20), 95% yield,
>99% ee; (c) CH3OCH2Cl (MOMCl), NaH, THF, 0 °C to rt; (d) 1
mol % of Pd(PPh3)4, K2CO3, MeOH, reflux, 90%.
SCHEME 2. Th e Syn th eses of
7,7′-Dia lk oxyl-2,2′-d ih yd r oxy-1,1′-d in a p h th yls (7)a
Most of the 7,7′-disubstituted binaphthols exhibited
high enantioselectivities of more than 90% ee (entries
2-11). Of them, 3 and 11 provided similar ee values as
BINOL under the same reaction conditions (entries 1, 2,
and 14). The substituent size on the ligand has no obvious
influence on the enantioselectivity. Enantioselectivities
ranging from 90% to 94% ee were provided by 7a -f.
Comparison of the results from 8a -c implied that
variation of dihedral angle by changing the ring size did
not lead to any influence on the enantioselectivity (entries
9-11). However, reactions catalyzed by Ti(IV) complexes
of 9a ,b, which were substituted by crown ether moiety
at their 7,7′-positions, provided lower enantioselectivities
(entries 12 and 13). The lower enantioselectivities might
be due to the coordination of zinc with the crown ether
of 9a ,b.
a
Reaction conditions: (a) RBr, CsOH, DMF, rt, 2 h; (b) aqueous
HCl, CHCl3/EtOH, 65 °C, 2 h.
multiethylene glycol ditosylate and subsequent hydroly-
sis with 6 N HCl (Scheme 3). The yields of products were
sharply dependent on the ring size. The yield is some-
what sacrificed when the ring size is too small or big.
For example, moderate yields of 38% and 47% were
observed with 8a and 8c, respectively.
(8) (a) Miyaura, N.; Yanagi, T.; Suzuki, A. Synth. Commun. 1981,
11, 513. (b) Suzuki, A. Acc. Chem. Res. 1982, 15, 178. (c) Suzuki, A. J .
Organomet. Chem. 1999, 576, 147.
(9) (a) Saa, J . M.; Dopico, M.; Martorell, G.; Garcia-Raso, A. J . Org.
Chem. 1990, 55, 991. (b) Kurz, L.; Lee, G.; Morgans, D., J r.; Waldyke,
M. J .; Ward, T. Tetrahedron Lett. 1990, 31, 6321.
(10) For Ti(IV)-BINOLs catalyzed alkynylzinc addition to aldehydes,
see: (a) Moore, D.; Pu, L. Org. Lett. 2002, 4, 1855. (b) Gao, G.; Moore,
D.; Xie, R. G.; Pu, L. Org. Lett. 2002, 4, 4143. (c) Lu, G.; Li, X.; Chan,
A. S. C. Chem. Commun. 2002, 172. (d) Li, X.; Lu, G.; Kwok, W. H.;
Chan, A. S. C. J . Am. Chem. Soc. 2002, 124, 12636. For Zn(II) catalyzed
alkynyl zinc addition to aldehydes, see: (e) Frantz, D. E.; Fa¨ssler, R.;
Tomooka, C. S.; Carreira, E. M. Acc. Chem. Res. 2000, 33, 373. (f)
Anand, N. K.; Carreira, E. M. J . Am. Chem. Soc. 2001, 123, 9687. (g)
Xu, M.; Pu, L. Org. Lett. 2002, 4, 4555.
A convenient reaction of 5 with trifluoromethane-
sulfonic anhydride in the presence of Et3N at 0 °C led to
10 with 87% yield. Suzuki coupling of 10 with phenyl-
boronic acid in the presence of 10 mol % of Pd(PPh3)4 and
with K3PO4 as base at 80 °C for 24 h furnished the
coupling products.8 Without purification in this step, the
crude product was subjected to a hydrolysis with 6 N HCl
to give 11 with total 67% yield (Scheme 4).
7922 J . Org. Chem., Vol. 68, No. 20, 2003

SCHEME 4. Th e Syn th esis of 11 by Su zu k i Cou p lin ga
a
Reaction conditions: (a) Tf2O, Et3N, 0 °C to rt, 87%; (b) 10 mol % of Pd(PPh3)4, PhB(OH)2, K3PO4, DME, 80 °C; (c) aqueous HCl,
CHCl3/EtOH, 65 °C, 2 h, 67% (2 steps).
TABLE 2. En a n tioselective P h en yla cetylen e Ad d ition
to Ald h yd es Ca ta lyzed by Ti(IV)-3
SCHEME 5. Th e Deter m in a tion of Absolu te
Con figu r a tion of New BINOLsa
aldehyde yield ee
R )
(%) (%)a
aldehyde
R )
yield ee
(%) (%)a
entry
entry
1
2
3
4
5
Ph
91
95
92
94
92
93
6
7
8
9
trans-PhCHdCH 69
93
92
4-MeC6H4 71
R-Naph
piperonyl
4-ClC6H4
3-MeC6H4
4-MeOC6H4
iPr
80
93
64
73
83
87
79
91
92b
93b
a
Reaction conditions: (a) 1 mol % of Pd(PPh3)4, iPr2NEt,
10 nBu
HCO2H, DMF, 80 °C; (b) aqueous HCl, CHCl3/EtOH, 65 °C, 2 h.
a
b
The ee values were determined on HPLC. Reactions were
carried out in the presence of 100 mol % of Ti(OiPr)4 and 40 mol
% of 3 in Et2O.
TABLE 1. En a n tioselective P h en yla cetylen e Ad d ition
to Ben za ld h yd e by Ti(IV)-BINOLs
level of stereocontrol in some asymmetric catalytic trans-
formations.
yield
ee
yield
ee
entry BINOLs
(%) (%)a
entry BINOLs
(%) (%)a
Exp er im en ta l Section
1
2
3
4
5
6
7
BINOL
3
79
91
92
78
72
84
79
95
95
92
94
91
92
94
8
9
7f
89
82
88
75
89
91
93
90
92
92
92
87
88
95
Gen er a l. The Kromasil CHI-TBB column was purchased from
Eka Chemicals AB. Chemicals were purchased from Acros and
used directly. Dichloromethane (CH2Cl2) and carbon tetrachlo-
ride (CCl4) were dried over CaH2. Petroleum ether (PE) and ethyl
acetate for column chromatography were distilled before use.
P r ep a r a tion of Op tica lly P u r e 7,7′-Dia lloxyl-2,2′-d ih y-
d r oxy-1,1′-d in a p h th yl (3). To a solution of chiral vanadium
catalyst (892.5 mg, 1.45 mmol) in CCl4 (100 mL) was added
7-alloxyl-2-naphthol (5.0 g, 25 mmol), and the resulting mixture
was stirred at 0 °C under O2 for about 4-6 days until the
reaction was complete (monitored by TLC). After removal of
solvent, the residue was purified by column chromatography on
silica gel (Rf 0.35, ethyl acetate/PE ) 1:5) to give crude 3 (5.0 g)
in 95% ee. The crude 3 was dissolved in a solvent mixture of
ethyl acetate (10 mL) and petroleum ether (200 mL). After the
solution remained at room temperature for 5 h, some precipitate
(3 in lower than 10% ee) formed. Removal of the precipitate and
concentration of the mother solution yielded 7,7′-dialloxyl-2,2′-
dihydroxy-1,1′-dinaphthyl (3) (4.7 g, 95%) as a colorless sticky
oil, [R]20D -234.8 (c 1.13, CHCl3), >99% ee determined by HPLC
(Chromasil CHI-TBB column, 10% IPA in hexane, flow rate 0.25
mL/min). 1H NMR (300 MHz, CDCl3) δ (ppm) 4.25 (m, 4H), 5.05
(s, 2H), 5.12 (m, 4H), 5.88(m, 2H), 6.48 (d, J ) 2.1 Hz, 2H), 7.05
(dd, J ) 8.8, 2.1 Hz, 2H), 7.22 (d, J ) 8.8 Hz, 2H), 7.78 (d, J )
8.8 Hz, 2H), 7.86 (d, J ) 8.8 Hz, 2H); 13C NMR (75 MHZ, CDCl3)
δ (ppm) 68.6, 104.4, 109.9, 115.1, 116.3, 118.0, 124.7, 129.8,
130.9, 132.7, 134.6, 153.2, 157.9; MS (EI) m/z 398 (M+); HRESI-
MS (positive ion) C26H23O4 ([M + H]+) requires 399.1596, found
399.1591. IR (KBr) υ 3502, 3078, 1620, 1512, 1452, 1270, 1214,
1022 cm-1. Anal. Calcd for C26H22O4: C, 78.37; H, 5.57. Found:
C, 78.45; H, 5.78.
8a
8b
8c
9a
9b
11
7a
7b
7c
7d
7e
10
11
12
13
14
a
The ee values were determined on HPLC.
The Ti(IV) complex of the optimal chiral ligand 3 was
then extended to the catalytic enantioselective pheny-
lacetylene additon to various types of aldehydes, includ-
ing aromatic aldehydes, aliphatic aldehydes, and an R,â-
unsaturated aldehyde. The results are given in Table 2.
All of examined aldehydes reacted smoothly with the
combined reagent of diethylzinc and phenylacetylene to
give high yields and excellent enantioselectivities. The
enantioselectivity was not significantly dependent on the
structure of the aldehyde. Enantioselectivities ranging
from 91% to 95% ee were observed with Ti(IV)-3 for all
of the tested aldehydes.
In summary, a family of optically pure binaphthols has
been prepared on the basis of our chiral oxovanadium
complex 1 catalyzed asymmetric oxidative coupling of
7-alloxyl-2-naphthol. Most of their Ti(IV) complexes
exhibited high enantioselectivity for the catalytic enan-
tioselective phenylacetylene additon to benzaldehyde.
7,7′-Dialloxyl-2,2′-dihydroxy-1,1′-dinaphthyl (3), prepared
directly from the asymmetric oxidative coupling, was
applied in the catalytic phenylacetylene additon to alde-
hydes with excellent enantioselectvities of up to 95% ee.
The results imply that these binaphthols have a high
Syn th esis of 7,7′-Dih yd r oxyl-2,2′-bis(m eth oxym eth oxy)-
1,1′-d in a p h th yl (5). To a suspension of NaH (1.92 g, 0.04 mol)
in dry THF (100 mL) was slowly added a solution of 3 (4.0 g,
0.01 mol) in THF (20 mL). After the reaction mixture was stirred
for 30 min, MOMCl (3.54 mL, 0.04 mmol) was added dropwise.
After the reaction solution was stirred for 5 h, the reaction was
J . Org. Chem, Vol. 68, No. 20, 2003 7923

quenched with saturated aqueous Na2CO3 (50 mL). The organic
layer was separated, and the aqueous solution was extracted
with ethyl acetate (100 mL × 2). The combined organic layer
was washed with brine and dried over anhydrous Na2SO4. After
removal of solvent, the residue was added to the solution of Pd-
(Ph3P)4 (115.5 mg) and K2CO3 (8.28 g) in MeOH (100 mL). After
the mixture was refluxed for about 5 h, the yellow solution was
concentrated and purified by column chromatography on silica
gel (Rf 0.42, ethyl acetate/PE ) 1:2) to yield 5 as pale yellow
2.4 Hz, 2H), 7.12 (d, J ) 8.8 Hz, 2H), 7.69 (d, J ) 8.8 Hz, 2H),
7.75 (d, J ) 8.8 Hz, 2H); 13C NMR (75 MHz, acetone-d6) δ (ppm)
67.6, 74.4, 109.7, 114.7, 117.9, 118.5, 126.2, 130.8, 131.1, 136.9,
155.5, 159.2; MS (EI) m/z 388 (M+); HRESI-MS (positive ion)
C
24H21O5 ([M + H]+) requires 389.1389, found 389.1384. IR (KBr)
υ 3439, 3061, 2945, 2860, 1660, 1620, 1510, 1447, 1210, 1161
cm-1. Anal. Calcd for C24H20O5: C, 74.21; H, 5.19. Found: C,
73.98; H, 5.32.
9b: Rf 0.21(ethyl acetate/PE ) 1:2), yield 51%, white solid,
needle crystal (3.8 g, 90%), mp 185.9-188.3 °C; [R]20 +3.8 (c
D
mp 104.5 °C dec; [R]20 -390 (c 0.278, CHCl3). 1H NMR (300
D
0.912, CHCl3). 1HNMR (300 MHz, acetone-d6) δ (ppm) 3.16 (s,
6H), 4.99 (d, J ) 6.8 Hz, 2H), 5.08 (d, J ) 6.8 Hz, 2H), 6.40 (d,
J ) 2.4 Hz, 2H), 6.99 (dd, J ) 8.7, 2.4 Hz, 2H), 7.41 (d, J ) 9.0
Hz, 2H), 7.81 (d, J ) 8.7 Hz, 2H), 7.89 (d, J ) 9.0 Hz, 2H), 8.34
(s, 2H); 13CNMR (75 MHz, acetone-d6) δ (ppm) 55.8, 95.5, 107.6,
114.8, 117.3, 120.5, 125.8, 129.6, 130.5, 136.6, 154.1, 156.6; MS
(EI) m/z 406 (M+); HRESI-MS (positive ion) C24H22O6Na ([M +
Na]+) requires 429.1314, found 429.1309. IR (KBr) υ 3365, 3286,
3060, 2923, 2850, 1624, 1511, 1237, 1078 cm-1. Anal. Calcd for
MHz, CDCl3) δ (ppm) 3.39-3.55 (m, 8H), 3.96-3.99 (m, 4H),
5.30 (br s, 2H), 6.44 (d, J ) 2.4 Hz, 2H), 7.06 (dd, J ) 8.9, 2.4
Hz, 2H), 7.22 (d, J ) 8.9 Hz, 2H), 7.77 (d, J ) 8.9 Hz, 2H), 7.86
(d, J ) 8.9 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ (ppm) 67.6,
68.8, 70.9, 105.9, 110.1, 115.2, 116.6, 124.7, 130.0, 131.0, 134.8,
152.8, 157.4; MS (EI) m/z 432 (M+); HRESI-MS (positive ion)
C26H25O6 ([M + H]+) requires 433.1651, found 433.1646. IR (KBr)
υ 3450, 3072, 2923, 2869, 1621, 1511, 1445, 1214, 1139 cm-1
.
Anal. Calcd for C26H24O6: C, 72.21; H, 5.59. Found: C, 72.48;
H, 5.46.
C
24H22O6: C, 70.92; H, 5.46. Found: C, 71.00; H, 5.46.
8a : Rf 0.37 (ethyl acetate/PE ) 1:3), yield 38%, white solid,
P r ep a r a tion a n d ch a r a cter iza tion of com p ou n d 11: To
a solution of 5 (203 mg, 0.5 mmol) in CH2Cl2 (15 mL) was added
triethylamine (101 mg, 1.0 mmol) and triflic anhydride (282 mg,
1.0 mmol) dropwise at 0 °C. After the mixture was stirred at
room temperature for 2 h, the reaction was quenched with water
(10 mL). The organic layer was separated, washed with 1 N HCl
and brine, and dried over anhydrous Na2SO4. After removal of
solvent, the residue was purified by column chromatography on
silica gel (PE:ethyl acetate ) 5:1) to yield 10 (292 mg, 87%). The
reaction solution of 10 (134 mg, 0.2 mmol), phenylboronic acid
(49 mg, 0.4 mmol), K3PO4 (212 mg, 1 mmol), and Pd(PPh3)4 (23
mg, 10% mmol) in DME (30 mL) was stirred at 80 °C for about
24 h. The solution was diluted with water (10 mL) and ethyl
acetate (30 mL). The organic layer was separated, washed with
brine, and dried over anhydrous Na2SO4. After removal of the
solvent, the crude product was hydrolyzed with 6 N HCl. The
reaction was worked up to give 11. Rf 0.33 (ethyl acetate/PE )
mp 218.7-219.2 °C; [R]20D -647.8 (c 0.14, CHCl3); 1H NMR (300
MHz, CDCl3) δ (ppm) 1.26-1.36 (m, 2H), 1.54-1.64 (m, 2H),
3.75-3.84 (m, 2H), 4.19-4.27 (m, 2H), 5.40 (br, 2H), 6.78 (d, J
) 2.3 Hz, 2H), 7.09 (dd, J ) 8.8, 2.3 Hz, 2H), 7.26 (d, J ) 8.8
Hz, 2H), 7.79 (d, J ) 8.8 Hz, 2H), 7.87 (d, J ) 8.8 Hz, 2H); 13C
NMR (75 MHz, CDCl3) δ (ppm) 22.2, 68.8, 110.2, 113.6, 116.1,
117.7, 125.7, 130.1, 131.2, 134.3, 152.7, 155.1; MS (EI) m/z 371
(M+ - H); HRESI-MS (positive ion) C24H21O4 ([M + H]+) requires
373.1440, found 373.1434. IR (KBr) υ 3429, 3068, 2950, 2883,
1620, 1510, 1441, 1265, 1194 cm-1. Anal. Calcd for C24H20O4:
C, 77.40; H, 5.41. Found: C, 77.51; H, 5.40.
8b: Rf 0.47 (ethyl acetate/PE ) 1:3), yield 61%; white solid,
1
mp 253.7 °C dec; [R]20 -453.9 (c 0.128, CHCl3); H NMR (300
D
MHz, CDCl3) δ (ppm) 1.19-1.27 (m, 4H), 1.33-1.36 (m, 2H),
1.42-1.46 (m, 2H), 3.81-3.88 (m, 2H), 3.99-4.04 (m, 2H), 5.32
(br, 2H), 6.51 (d, J ) 2.3 Hz, 2H), 7.05 (dd, J ) 8.9 Hz, 2.4 Hz,
2H), 7.23 (d, J ) 8.8 Hz, 2H), 7.78 (d, J ) 8.8 Hz, 2H), 7.86 (d,
J ) 8.9 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ (ppm) 23.2, 27.4,
67.0, 109.0, 110.1, 115.4, 116.4, 124.9, 129.9, 131.1, 134.8, 152.8,
157.2; MS (EI) m/z 400 (M+); HRESI-MS (positive ion) C26H25O4
([M + H]+) requires 401.1753, found 401.1747. IR(KBr) υ 3504,
3066, 2932, 2903, 1620, 1510, 1451, 1265, 1203, 1062 cm-1. Anal.
Calcd for C26H24O4: C, 77.98; H, 6.04. Found: C, 78.09; H, 6.28.
8c: Rf 0.18 (ethyl acetate/PE ) 1:5), yield 47%; white solid,
1:3), yield 67%, white solid, mp 98.5-100.2 °C; [R]20 -547.5 (c
D
1
0.128, CHCl3). H NMR (300 MHz, CDCl3) δ (ppm) 5.12 (s, 2H),
7.26-7.44 (m, 14H), 7.65-7.66 (m, 2H), 7.97-8.02 (m, 4H); 13
C
NMR (75 MHz, CDCl3) δ (ppm) 110.9, 117.8, 122.0, 124.0, 127.4,
127.5, 128.4, 128.7, 129.0, 131.3, 133.6, 140.4, 141.0, 153.2; MS
(EI) m/z 438 (M+); HRESI-MS (positive ion) C32H23O2 ([M + H]+)
requires 439.1698, found 439.1693. IR (KBr) υ 3502, 3056, 1619,
1512, 1492, 1214, 1164, 1026 cm-1. Anal. Calcd for C32H22O4:
C, 87.65; H, 5.06. Found: C, 87.45; H, 4.96.
mp 95.5-96.4 °C dec; [R]20 -360.9 (c 0.112, CHCl3); 1HNMR
D
(300 MHz, CDCl3) δ (ppm) 1.03-1.11 (m, 4H), 1.23-1.27 (m,
4H), 1.41-1.51 (m, 4H), 3.77-3.91 (m, 4H), 5.14 (s, 2H), 6.45
(d, J ) 2.4 Hz, 2H), 7.03 (dd, J ) 8.8 Hz, 2.4 Hz, 2H), 7.22 (d, J
) 8.8 Hz, 2H), 7.78 (d, J ) 8.8 Hz, 2H), 7.87 (d, J ) 8.8 Hz, 2H);
13C NMR (75 MHz, CDCl3) δ (ppm) 24.3, 27.6, 27.4, 66.7, 105.9,
109.9, 115.0, 116.2, 124.7, 129.9, 131.1, 135.1, 153.0, 157.8; MS
(EI) m/z 428 (M+); HRESI-MS (positive ion) C28H29O4 ([M + H]+)
requires 429.2066, found 429.2061. IR (KBr) υ 3448, 3061, 2932,
2858, 1621, 1512, 1452, 1214, 1066 cm-1. Anal. Calcd for
Ack n ow led gm en t. We are grateful for financial
support from the National Natural Science Foundation
of China (203900505).
Su p p or tin g In for m a tion Ava ila ble: Preparation and
characterization of 7a -f; general experimental procedure and
HPLC analysis for the enantioselective phenylacetylene ad-
dition to aldehydes; 1H NMR and 13C NMR spectra for 5, 7a -
f, 8a -c, 9a ,b and 11. This material is available free of charge
via the Internet at http://pubs.acs.org.
C
28H28O4: C, 78.48; H, 6.59. Found: C, 78.27; H, 6.53.
9a : Rf 0.40 (ethyl acetate/PE ) 1:2), yield 67%, white solid,
mp 89.5 °C dec; [R]20 -485.7 (c 0.112, CHCl3). 1H NMR (75
D
MHz, acetone-d6) δ (ppm) 3.38-3.46 (m, 4H), 3.80-3.85 (m, 2H),
4.08-4.11 (m, 2H), 6.81 (d, J ) 2.4 Hz, 2H), 6.88 (dd, J ) 8.8,
J O034831+
7924 J . Org. Chem., Vol. 68, No. 20, 2003