Facile synthesis of 11-membered C2 symmetric chiral binaphthyl ketone via co(salen)-catalyzed macrolactonization

Full text of DOI:10.1021/jo000192g

J . Org. Chem. 2000, 65, 4213-4216
4213
Sch em e 2
F a cile Syn th esis of 11-Mem ber ed C2
Sym m etr ic Ch ir a l Bin a p h th yl Keton e via
Co(sa len )-Ca ta lyzed Ma cr ola cton iza tion
Tooru Kuroda, Ritsuo Imashiro, and Masahiko Seki*
Product & Technology Development Laboratory,
Tanabe Seiyaku Co., Ltd., 3-16-89, Kashima, Yodogawa-ku,
Osaka 532-8505, J apan
Received February 11, 2000
In tr od u ction
Macrocyclic lactones have received considerable atten-
tion as valuable building blocks for such compounds as
drugs and natural products.1 Development of their ef-
ficient synthetic method has thus been a subject of keen
interest. Yang has developed an 11-membered C2 sym-
metric chiral ketone 1, an efficient catalyst for a dioxi-
rane-mediated catalytic asymmetric epoxidation.2
most critical step in the synthesis is the use of a catalytic
process for the formation of the 11-membered ring from
(R)-1,1′-binaphthyl-2,2′-dicarboxylic acid monoglycidyl
ester 3. We envisaged that the macrolactonization would
take place under higher concentration conditions if the
cyclization could be effected only by the interaction with
a catalyst, which allowed a low concentration of the
reactive intermediate 5 (Scheme 2). We report herein a
practical synthesis of the 11-membered chiral ketone 1
through a novel and unprecedentedly efficient Co(salen)-
catalyzed macrolactonization of 3.
One of the main challenges in synthesizing the chiral
ketone 1 is efficiently making the 11-membered macro-
cyclic lactone skeleton. However, the reported procedure
based on the condensation of (R)-1,1′-binaphthyl-2,2′-
dicarboxylic acid 2 with 1, 3-dihydroxyacetone dimer
requires Mukaiyama reagent and ca. 300 volume of
solvent per weight of the substrate (300 v/w) to obtain
only 28% yield of the cyclized product.2a In our previous
paper3 has been reported an intramolecular Ullmann
reaction for the formation of the 11-membered ring. While
the reaction provides the ring system in 67% yield, it still
requires a dilution method (reaction solvent 40 v/w), and
the preparation of the substrate, a diiodide, requires
tedious procedures and expensive reagents.
Resu lts a n d Discu ssion
The monoglycidyl ester 3 was readily prepared from
(R)-1,1′-binaphthyl-2,2′-dicarboxylic acid 24 through the
formation of acid anhydride(s) followed by esterification
with glycidol. As shown in Table 1, the transformation
was best conducted by the use of thionyl chloride (SOCl2)
and triethylamine (Et3N) for the formation of the acid
anhydride(s). The reaction was found to give a mixture
of polymeric acid anhydrides whose major product proved
to be a dimer 6 as consolidated by the X-ray crystal-
Sch em e 1
lographic analysis.6 Treatment of the crude mixture of
the acid anhydrides with glycidol in the presence of Et3N
(2) (a) Yang, D.; Yip, Y.-C.; Tang, M.-W.; Wong, M.-K.; Zheng, J .-
H.; Cheung, K.-K. J . Am. Chem. Soc. 1996, 118, 491. (b) Yang, D.;
Wang, X.-C.; Wong, M.-K.; Yip, Y.-C.; Tang, M.-W. J . Am. Chem. Soc.
1996, 118, 11311. (c) Yang, D.; Wong, M.-K.; Yip, Y.-C.; Wang, X.-C.;
Tang, M.-W.; Zheng, J .-H.; Cheung, K.-K. J . Am. Chem. Soc. 1998,
120, 5943.
In our improved synthesis of the chiral ketone 1, we
employed a synthetic scheme outlined in Scheme 1. The
(3) Seki, M.; Furutani, T.; Hatsuda, M.; Imashiro, R. Tetrahedron
Lett. 2000, 41, 2149.
(4) The enantiopure dicarboxylic acid 2 (R-isomer) was prepared
either by an optical resolution of the racemic dicarboxylic acid (()-2
using brucine5a or by our procedure based on an enzymatic resolution.5b
(1) For a recent review, see: Roxburgh, C. J . Tetrahedron 1995, 51,
9767.
10.1021/jo000192g CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/07/2000

4214 J . Org. Chem., Vol. 65, No. 13, 2000
Notes
Ta ble 1. P r ep a r a tion of Mon oglycid yl Ester 3 fr om 2a
Screening of the catalyst is described in Table 3. The
reactions were conducted in 20 v/w of an appropriate
solvent in the presence of the catalyst (5 mol %) and N,N-
diisopropylethylamine (i-Pr2NEt) (1.1 equiv) at ambient
temperature in air atmosphere.10 Naturally occurring Co-
(salen) complex, salcomine 8, provided 4 in 43% yield
(Table 3, entry 1). The use of conformationally more rigid
Co(salen) complexes 9 and 10 derived from cyclic di-
amines gave better yields (49% and 68%, respectively)
(Table 3, entries 2 and 3). The yield was remarkably
elevated by employing tetrahydrofuran (THF) as the
solvent in place of dichloromethane (CH2Cl2) (80% yield
with 9 used as the catalyst) (Table 3, entry 4). Further-
more, a Co(salen) complex 11 prepared from racemic
trans-1,2-diaminocyclohexane and 3,5-di-tert-butylsali-
cylaldehyde was found to provide 4 in 95% yield (Table
3, entry 5). The diamine ligands of the Co(salen) com-
plexes have a crucial role for the catalytic cyclization:
cobalt(II) chloride or other metal salts such as Ti(Oi-Pr)4,
FeCl3 and ZnCl2 alone gave much poorer yields of 4
(Table 3, entries 6-9).
yield (%)
entry
reagent
3
7
1
2
3
4
ClP(O)(OPh)2
POCl3
TsCl
77
17
79
80
5
28
8
SOCl2
9
a
The reactions were conducted using (1) 2 (1.0 mmol), reagent
(1.0 mmol), Et3N (2.2 mmol); (2) glycidol (1.3 mmol), Et3N (1.2
mmol), DMAP (0.1 mmol).
and a catalytic amount of 4-(dimethylamino)pyridine
(DMAP) provided the desired monoglycidyl ester 3 in 80%
yield along with a minor amount of a diglycidyl ester 7
(9% yield) (Table 1, entry 4).
The 11-membered cyclic alcohol 4 thus obtained was
readily oxidized with manganese(IV) oxide3 to provide the
desired chiral ketone 1 in 91% yield (Scheme 3). Com-
Sch em e 3
The cyclization of the monoglycidyl ester 3 was first
investigated by the use of quaternary ammonium hy-
droxide or its congeners (n-Bu4NX + MOH) (Table 2).
Applying the conditions for the intermolecular reaction
of a glycidyl ester with a carboxylic acid8 to the present
intramolecular cyclization of 3, the desired product 4 was
obtained in 44% yield by the use of 20 v/w of solvent
(Table 2, entry 2). The method is superior to the reported
procedure (28% yield, reaction solvent ca. 300 v/w) to
form the 11-membered ring.2a This result demonstrates
an efficiency of the catalytic process to form the 11-
membered ring of 1.
parison of the product 1 with an authentic sample
revealed identity with respect to IR, H NMR, and mass
spectra and specific rotation. The optical integrity of the
product 1 obtained by this method was confirmed by
chiral HPLC analysis.
1
Ta ble 2. Ma cr ola cton iza tion of 3 to 4 Ca ta lyzed by
Qu a ter n a r y Am m on iu m Hyd r oxid ea
In conclusion, a practical synthesis of the 11-membered
chiral ketone 1 was accomplished. The chiral ketone 1
was synthesized in 69% overall yield in three steps from
(R)-1,1′-binaphthyl-2,2′-dicarboxylic acid 2 through the
Co(salen) complex 11-catalyzed macrolactonization. The
present synthesis is efficient in terms of simple opera-
tions, ready availability of the reagents, and a high yield
of the cyclization step without the need for high-dilution
methods. This would permit the accessibility of chiral
ketone 1 by a practical large-scale preparation.
entry
catalyst
base
period (h)
yield (%)
1
2
3
4
n-Bu4NHSO4
n-Bu4NI
n-Bu4NOH
n-Bu4NI
NaOH
LiOH
29
7
7
33
44
38
0
K2CO3
7
a
The reactions were conducted in refluxing EtOH (4 mL) using
3 (0.5 mmol), catalyst (5 mol %), and base (7.5 mol %).
To further improve the yield, development of a more
efficient catalyst that can properly orientate the carboxyl
group in 3 toward the epoxide was needed. J acobsen et
al. reported an enantioselective ring opening of epoxides
with carboxylic acids in the presence of a Co(salen)
complex.9 We envisioned a possible use of the intermo-
lecular reaction for the present intramolecular cycliza-
tion.
Exp er im en ta l Section
Gen er a l Meth od s. Melting points are uncorrected. 1H NMR
spectra were recorded with Me4Si as an internal standard.
Optical rotations were measured at the indicated temperature
with
a sodium lamp (D line, 589 nm). Silica gel column
chromatography was performed using Kieselgel 60 (E. Merck).
Thin-layer chromatography (TLC) was carried out on E. Merck
0.25 mm precoated glass-backed plates (60 F254). Development
was accomplished using 5% phosphomolybdic acid in ethanol/
heat or visualized by UV light where feasible. Tetrahydrofuran
(THF) was distilled from sodium/benzophenone ketyl. Dichlo-
romethane (CH2Cl2) was distilled from P2O5. Other solvents and
reagents were used as received. Co(salen) complexes 9, 10, and
(5) (a) Kanoh, S.; Hongoh, Y.; Motoi, M.; Suda, H. Bull. Chem. Soc.
J pn. 1988, 61, 1032. (b) Furutani, T.; Hatsuda, M.; Imashiro, R.; Seki,
M. Tetrahedron Asymmetry 1999, 10, 4763.
(6) X-ray data for compound
6 have been deposited with the
Cambridge Crystallographic Data Centre. Miyano et al. reported the
polymeric acid anhydrides were formed in the reaction of 2 with
dicyclohexylcarbodiimide.7
(7) Oi, S.; Matsuzaka, Y.; Yamashita, J .; Miyano, S. Bull. Chem.
Soc. J pn. 1989, 62, 956.
(8) Ikeda, I.; Gu, X.-P.; Miyamoto, I.; Okahara, M. J . Am. Oil Chem.
Soc. 1989, 66, 822.
(9) J acobsen, E. N.; Kakiuchi, F.; Konsler, R. G.; Larrow, J . F.;
Tokunaga, N. Tetrahedron Lett. 1997, 38, 773.
(10) The reactive species of the present macrolactonization (Co(II)
complex or Co(III) complex) is not clear. The reaction rate did not
change either under strictly anaerobic conditions or under an oxygen
atmosphere.

Notes
J . Org. Chem., Vol. 65, No. 13, 2000 4215
Ta ble 3. Ma cr ola cton iza tion of 3 to 4 Ca ta lyzed by Co(sa len )a
a
The reactions were conducted in 2 mL of solvent at room temperature using 3 (0.25 mmol), i-Pr2NEt (0.275 mmol), and catalyst (5
mol %).
11 were prepared from the corresponding salen ligand and Co-
(R)-Diglycid yl 1,1′-bin a p h th yl-2,2′-d ica r boxyla te (7): col-
orless powder; 1H NMR (CDCl3) δ 8.22 (dd, J ) 4.0, 8.7 Hz, 2H),
8.03 (d, J ) 8.7 Hz, 2H), 7.96 (d, J ) 8.2 Hz, 2H), 7.58-7.50 (m,
2H), 7.30-7.13 (m, 2H), 7.13-7.02 (m, 2H), 4.08-3.99 (m, 2H),
3.88-3.77 (m, 2H), 2.69-2.62 (m, 2H), 2.62-2.51 (m, 2H), 2.32-
2.21 (m, 2H); MS m/z 454 (M+).
(II) acetate tetrahydrate according to the literature.11
(R)-1,1′-Bin a p h th yl-2,2′-d ica r boxylic Acid Mon oglycid yl
Ester (3). To a solution of (R)-1,1′-binaphthyl-2,2′-dicarboxylic
acid 2 (342 mg, 1.0 mmol) and Et3N (307 mL, 2.2 mmol) in CH2-
Cl2 (5 mL) was added SOCl2 (143 mg, 1.2 mmol) in CH2Cl2 (1
mL) at room temperature over 1 h, and the mixture was stirred
overnight. After evaporation of the solvent, the residue was
azeotroped with toluene, and the solution was evaporated to
dryness. To the residue were successively added CH2Cl2 (5 mL),
Et3N (170 mL, 1.2 mmol), glycidol (101 mg, 1.3 mmol), and
DMAP (12 mg, 0.1 mmol) at room temperature. After stirring
for 1 h at room temperature, the reaction mixture was quenched
by addition of 10% aqueous citric acid and extracted with AcOEt.
The organic layer was washed with water and brine and dried
over MgSO4. After evaporation of the solvent, the residue was
purified by silica gel column chromatography (CHCl3/AcOEt )
50:1 to 30:1) to give monoglycidyl ester 3 (319 mg, 80% yield)
and diglycidyl ester 7 (43 mg, 9% yield). Data for 3: colorless
powder; 1H NMR (CDCl3) δ 8.19-8.11 (m, 2H), 8.03-7.92 (m,
4H), 7.56-7.48 (m, 2H), 7.32-7.19 (m, 2H), 7.02 (d, J ) 8.7 Hz,
2H), 4.07-3.89 (m, 1H), 3.89-3.77 (m, 1H), 2.73-2.63 (m, 1H),
2.56-2.50 (m, 1H), 2.30-2.21 (m, 1H); IR (KBr) 3435, 3070,
3003, 1723, 1621, 1598 cm-1; MS m/z 398 (M+).
Dim er ic a n h yd r id e (6): colorless crystals; mp 227-243 °C;
[R]22 +771 (c 0.10, CHCl3); 1H NMR (CDCl3) δ 7.95 (d, J ) 8.1
D
Hz, 4H), 7.88 (d, J ) 8.6 Hz, 4H), 7.61-7.50 (m, 8H), 7.23-7.31
(m 4H), 6.96 (d, J ) 7.9 Hz, 4H); IR (KBr) 3050, 1775, 1730,
1712, 1614, 1594 cm-1; SIMS m/z 648 (M+).
(R)-5H-Din a p h th o[2,1-g:1′,2′-i][1,5]d ioxa cyclou n d ecin -6-
h yd r oxy-3,9(7H)-d ion e (4). To a stirred solution of 3 (100 mg,
0.25 mmol) in THF (2 mL) were added i-Pr2NEt (35 mg, 0.275
mmol) and Co(salen) complex 11 (7.5 mg, 0.0125 mmol) at room
temperature. The mixture was stirred at the same temperature
for 142 h. The resulting mixture was diluted with AcOEt, washed
with saturated aqueous NaHCO3 and brine, dried over MgSO4,
and filtered. The filtrate was concentrated in vacuo, and the
resulting solids were purified by silica gel column chromatog-
raphy (hexane/AcOEt ) 2:1) to give 4 (95 mg, 95% yield) as
colorless crystals: mp 256-257 °C; [R]25 -230 (c 1.01, CHCl3);
D
optical purity ) 100% ee (HPLC analysis, Daicel Chiralcel OD,
hexane/i-PrOH ) 10:1, 1.0 mL/min, 18 min (S-enantiomer), 25
min (R-enantiomer)); 1H NMR (CDCl3) δ 8.02-7.93 (m, 4H), 7.65
(dd, J ) 8.5, 11.4 Hz, 2H), 7.56-7.49 (m, 2H), 7.31 (d, J ) 7.4
Hz, 2H), 7.17 (d, J ) 8.6 Hz, 2H), 4.85 (dd, J ) 3.2, 12.4 Hz,
(11) (a) West, B. O. J . Chem. Soc. 1954, 395. (b) Leung, W.-H.; Chan,
E. E. Y.; Chow, E. K. F.; Williams, I. D.; Peng, S.-M. J . Chem. Soc.,
Dalton Trans. 1996, 1229.

4216 J . Org. Chem., Vol. 65, No. 13, 2000
Notes
1H), 4.57 (dd, J ) 8.3, 10.7 Hz), 4.29 (m, 1H), 4.12 (dd, J ) 6.7,
10.7 Hz, 1H), 4.03 (dd, J ) 1.3, 12.4 Hz, 1H), 2.11 (d, J ) 8.4
Hz, 1H); IR (KBr) 3520, 3420, 3050, 2940, 2880, 1744, 1720, 1592
cm-1; MS m/z 398 (M+). Anal. Calcd for C25H18O5: C, 75.37; H,
4.55. Found: C, 75.37; H, 4.47.
Chiralcel OD, hexane/i-PrOH ) 10:1; 1.0 mL/min, 16 min (S-
enantiomer), 26 min (R-enantiomer)); 1H NMR (CDCl3) δ 8.04
(d, J ) 8.5 Hz, 2H), 7.97 (d, J ) 8.2 Hz, 2H), 7.66 (d, J ) 8.5 Hz,
2H), 7.56 (dd, J ) 1.5, 6.6 Hz, 2H), 7.30-7.37 (m, 2H), 7.25 (d,
J ) 14.1 Hz, 2H), 5.56 (d, J ) 15.4 Hz, 2H), 4.20 (d, J ) 15.4
Hz, 2H); IR (KBr) 3550, 3430, 3050, 2970, 2925, 1755, 1730, 1593
cm-1; MS m/z 396 (M+). Anal. Calcd for C25H16O5: C, 75.71; H,
4.07. Found: C, 75.41; H, 3.96.
(R)-5H -Din a p h t h o[2,1-g:1′,2′-i][1,5]d ioxa cyclou n d ecin -
3,6,9(7H)-tr ion e (1). To a suspension of 4 (200 mg, 0.5 mmol)
in CH3CN (15 mL) was added MnO2 (1.2 g, 13.8 mmol). The
mixture was stirred at room temperature for 24 h and filtered
through a pad of Celite. The undissolved solid was extracted with
CHCl3. The extracts were combined and evaporated. The crystals
formed were washed with i-PrOH (3 mL) to give 1 (181 mg, 91%)
Ack n ow led gm en t. We are indebted to Mr. Hajime
Hiramatsu of Tanabe Seiyaku Co., Ltd., for the X-ray
analysis.
as colorless crystals: mp 300 °C (dec); [R]27 +10.9 (c 1.02,
D
CHCl3); optical purity ) 100% ee (HPLC analysis, Daicel
J O000192G