1936
D.-M. Du et al. / Tetrahedron 59 (2003) 1933–1938
the sign of the specific rotation.18 Solvents used were
purified and dried by standard procedures.
127.9, 127.4, 127.2, 126.6, 65.4, 63.4, 58.2, 36.6. MS
(FAB): 549 (Mþ1). Anal. for C35H36O4N2 Calcd (%) C,
76.64; H, 6.56; N, 5.11. Found (%): C, 76.72; H, 6.66; N,
5.20.
3.1.1. 6,6-Bis[N-(10S)-(10-isobutylhydroxyethyl)amido]-
dibenzo[a,c]-1,3-cycloheptadiene (7a). General procedure
I. To a solution of diethyl dibenzo[a,c]-1,3-cyclohepta-
diene-6,6-dicarboxylate 6 (1.0 g, 2.96 mmol) in CH3OH
(10 mL) was added NaOH solution (10 mL, 2N). The
mixture was refluxed for 8 h, then the methanol was
removed in vacuo. The residue was cooled to 08C and
acidified with aqueous HCl (6N). The acidified mixture was
extracted with ether (10 mL£3), the organic layer was dried
with anhydrous Na2SO4 and evaporated. The obtained white
solid was directly refluxed with SOCl2 (5 mL) for 2 h, the
excess SOCl2 was removed in vacuo. Benzene (10 mL) was
added and the solvent was removed again to dryness to
remove the trace of SOCl2 and afford the diacyl dichloride.
The diacyl dichloride in CH2Cl2 (20 mL) was added
dropwise to a solution of L-leucinol (0.75 g, 6.4 mmol)
and Et3N (4 mL, 28.9 mmol) in CH2Cl2 (20 mL) at 08C and
stirred at room temperature for 4 h. The reaction mixture
was washed with water (5 mL£2). The organic layer was
dried over anhydrous Na2SO4 and concentrated to give
crude solid. Purification by silica gel column chroma-
tography (40% ethyl acetate in petroleum ether) afforded the
dihydroxy diamide 7a 0.96 g (67.6%). Mp 162–163.58C.
[a]2D0¼26.8 (c¼0.8, CHCl3). IR (KBr): n 3406, 2958, 1639,
1534, 1451, 1262 cm21. 1H NMR (CDCl3): d 7.39–7.20 (m,
8H), 6.20 (br s, 2H), 4.02–4.18 (m, 2H), 3.73 (t, J¼6.4 Hz,
2H), 3.41–3.25 (m, 6H), 2.80 (br s, 2H), 1.55–1.25 (m, 6H),
0.86 (d, J¼7.0 Hz, 12H). 13C (50 MHz, CDCl3): d 172.0,
140.6, 135.6, 127.8, 127.3, 65.3, 58.1, 49.8, 36.9, 24.8, 22.7,
21.7, 18.2. MS (FAB): 481 (Mþ1). Anal. for C29H40O4N2
Calcd (%) C, 72.50; H, 8.33; N, 5.83. Found (%): C, 72.44;
H, 8.20; N, 5.68.
3.1.4. 6,6-Bis[N-(10S)-(10-phenylhydroxyethyl)amido]-
dibenzo[a,c]-1,3-cycloheptadiene (7d). Following general
procedure I, diethyl dibenzo[a,c]-1,3-cycloheptadiene-6,6-
dicarboxylate 6 (1.0 g, 2.96 mmol), L-phenylglycinol (0.88 g,
6.4 mmol) and Et3N (4 mL, 28.9 mmol) to afford the
dihydroxy diamide 7d 1.08 g (70.1%). Mp 181–1838C.
[a]2D0¼250.0 (c¼0.44, CHCl3). IR (KBr): n 3406, 2936,
1
1641, 1539, 1453, 1262 cm21. H NMR (CDCl3): d 7.37–
7.16 (m, 18H), 6.90 (br s, 2H), 5.16–5.09 (m, 2H), 3.91–
3.80 (m, 4H), 3.50–2.80 (m, 6H). 13C (CDCl3): d 171.8,
140.4, 135.3, 129.8, 127.9, 127.8, 127.6, 127.5, 126.6, 65.9,
65.6, 55.9, 37.5. MS (FAB): 521 (Mþ1). Anal. for
C33H32O4N2 Calcd (%) C, 76.15; H, 6.15; N, 5.38. Found
(%): C, 76.34; H, 6.20; N, 5.14.
3.1.5. 6,6-Bis[N-(10R)-(10-phenylhydroxyethyl)amido]-
dibenzo[a,c]-1,3-cycloheptadiene (7e). Following general
procedure I, diethyl dibenzo[a,c]-1,3-cycloheptadiene-6,6-
dicarboxylate
6 (1.0 g, 2.96 mmol), D-phenylglycinol
(0.88 g, 6.4 mmol) and Et3N (4 mL, 28.9 mmol) to afford
the dihydroxy diamide 7e 1.12 g (72.7%). Mp 175–1778C.
[a]2D0¼þ69.6 (c¼0.56, CHCl3). IR (KBr): n 3406, 2936,
1
1640, 1536, 1456, 1262 cm21. H NMR (CDCl3): d 7.38–
7.16 (m, 18H), 6.91 (br s, 2H), 5.18–5.09 (m, 2H), 3.91–
3.80 (m, 4H), 3.40–2.80 (m, 6H). 13C (CDCl3): d 171.7,
140.3, 135.2, 129.9, 127.8, 127.7, 127.6, 127.5, 126.5, 65.7,
65.5, 55.8, 37.2. MS (FAB): 521 (Mþ1). Anal. for
C33H32O4N2 Calcd (%) C, 76.15; H, 6.15; N, 5.38. Found
(%): C, 76.38; H, 6.28; N, 5.19.
3.1.6. 6,6-Bis[(40S)-40-isobutyloxazolin-20-yl]-dibenzo-
[a,c]-1,3-cycloheptadiene (5a). General procedure II. To
an ice cold solution of the dihydroxy diamide 7a (1.20 g,
2.5 mmol) and Et3N (2 mL, 14 mmol) in CH2Cl2 (20 mL)
was added MsCl (0.60 g, 5.2 mmol) slowly. The mixture
was allowed to warm to room temperature and was stirred
for 1 h. The mixture was washed with water (5 ml). The
organic layer was dried over anhydrous Na2SO4 and
concentrated to dryness in vacuo to give the crude
bismesylate as a yellow oil. The crude bismesylate was
dissolved in CH3OH (20 mL) and was treated with NaOH
solution (4 mL, 1N) at room temperature for 12 h. The
methanol was removed in vacuo and 30 mL CH2Cl2 was
added to it. The solution was washed with water (5 mL£2).
The organic layer was dried over anhydrous Na2SO4 and
concentrated in vacuo to give a pale yellow oil. Purification
by silica gel column chromatography (petroleum ether–
ethyl acetate 5:1) to afford colorless viscous oil 5a 0.91 g
(81.9% yield). [a]2D0¼228.9 (c¼0.95, CHCl3). IR (KBr): n
3.1.2. 6,6-Bis[N-(10S)-(10-isopropylhydroxyethyl)amido]-
dibenzo[a,c]-1,3-cycloheptadiene (7b). Following general
procedure I, from diethyl dibenzo[a,c]-1,3-cyclohepta-
diene-6,6-dicarboxylate 6 (1.0 g, 2.96 mmol), L-valinol
(0.66 g, 6.4 mmol) and Et3N (4 mL, 28.9 mmol) to afford
the dihydroxy diamide 7b 0.88 g (65.7%). Mp 170–1728C.
[a]2D0¼214.6 (c¼0.24, CHCl3). IR (KBr): n 3406, 2960,
1
1637, 1539, 1451, 1262 cm21. H NMR (CDCl3): d 7.42–
7.25 (m, 8H), 6.24 (br s, 2H), 3.83–3.70 (m, 4H), 3.60–3.25
(m, 4H), 3.05–2.70 (m, 4H), 1.82–1.73 (m, 2H), 0.92 (d,
J¼7.0 Hz, 6H), 0.88 (d, J¼8.8 Hz, 6H). 13C (CDCl3): d
172.5, 140.3, 135.5, 130.4, 128.0, 127.6, 65.9, 63.8, 57.4,
37.2, 28.9, 19.6, 19.0. MS (FAB): 453 (Mþ1). Anal. for
C27H36O4N2 Calcd (%) C, 71.68; H, 7.96; N, 6.19. Found
(%): C, 71.73; H, 7.82; N, 6.06.
3.1.3. 6,6-Bis[N-(10S)-(10-benzylhydroxyethyl)amido]-
dibenzo[a,c]-1,3-cycloheptadiene (7c). Following general
procedure I, from diethyl dibenzo[a,c]-1,3-cyclohepta-
diene-6,6-dicarboxylate 6 (1.0 g, 2.96 mmol), L-phenyl-
alaninol (0.97 g, 6.4 mmol) and Et3N (4 mL, 28.9 mmol) to
afford the dihydroxy diamide 7c 1.15 g (70.8%). Mp 196–
1988C. [a]2D0¼þ74.2 (c¼0.48, CHCl3). IR (KBr): n 3406,
1
3010, 2966, 1654, 1508, 1482 cm21. H NMR (CDCl3):
d 7.25–7.44 (m, 8H), 4.36 (t, J¼8.4 Hz, 2H), 4.22–4.07
(m, 2H), 3.89 (s, 2H), 3.26–2.90 (m, 4H), 1.86–1.42
(m, 4H), 1.36–1.19 (m, 2H), 0.88 (d, J¼3.8 Hz, 12H). 13C
NMR (50 MHz, CDCl3): d 166.1, 140.9, 138.1, 127.9,
127.4, 127.1, 73.5, 65.8, 64.6, 45.6, 37.6, 25.3, 22.8. MS
(EI): 444 (Mþ, 100), 429 (7), 387 (20), 318 (45), 304 (32).
HRMS (EI): calcd for C29H36O2N2 444.2777, found:
444.2777.
1
2932, 1640, 1539, 1453, 1262 cm21. H NMR (CDCl3):
d 7.34–7.12 (m, 18H), 6.31 (br s, 2H), 4.38–4.20 (m,
2H), 3.85–3.70 (m, 2H), 3.50–3.44 (m, 2H), 2.90–2.56 (m,
8H). 13C (CDCl3): d 171.9, 140.2, 137.2, 135.3, 128.5,