W. Adam et al. / Tetrahedron: Asymmetry 14 (2003) 1355–1361
1359
1,8-dicarboxylic anhydride and 1.13 g (15.0 mmol) of
glycine in 30 mL DMF was stirred for 4 h at 100°C.
The reaction mixture was cooled to room temperature
(ca. 20°C), diluted with 30 mL of ethyl acetate, and
washed with water (2×15 mL). The organic phase was
dried over MgSO4 and the solvent removed (50°C, 8
torr). The crude product was recrystallized from ethyl
acetate to give 2.65 g (10.4 mmol, 69% yield) of the
desired carboxylic acid as colorless powder; mp 272–
4.2.4.
benz[de]isoquinoline-2(3H)-acetamide, 4. To a suspen-
sion of 593 mg (2.97 mmol) of the
N-(Diphenylmethyl)-N-hydroxy-1,3-dioxo-1H-
N-hydroxy-a-phenylbenzenemethanamine in 30 mL
CH2Cl2 was added dropwise a solution of 812 mg
(2.97 mmol) of 1,3-dioxo-1H-benz[de]isoquinoline-
2(3H)-acetyl chloride in 34 mL CH2Cl2 at room tem-
perature (ca. 20°C). The mixture was stirred for 1 h,
the colorless precipitate was collected by filtration and
recrystallized from hot acetone. The product was dried
(20°C at 1 torr) to afford 503 mg (1.15 mmol, 39%
yield) of the hydroxamic acid 4 as colorless powder;
1
273°C (lit.:18 250°C); H NMR (200 MHz, d6-DMSO)
l 4.73 (s, 2H, CH2), 7.86 (t, J=8 Hz, 2H, H arom.),
8.49–8.54 (m, 4H, H arom.); 13C NMR (63 MHz,
d6-DMSO) l 41.2 (t, CH2), 121.4 (2×s, C arom.), 127.3
(2×d, C arom.), 127.3 (s, C arom.), 131.1 (2×d, C
arom.), 131.3 (s, C arom.), 134.8 (2×d, C arom.), 163.1
(2×s, C(O)–N), 169.3 (s, CO2H).
1
mp 184–185°C; H NMR (200 MHz, d6-DMSO) l 5.11
(s, 2H, CH2), 6.70 (s, 1H, CHPh2), 7.27–7.43 (m, 10H,
2×Ph), 7.86–7.94 (m, 2H, H arom.), 8.49–8.54 (m, 4H,
H arom.); 13C NMR (63 MHz, d6-DMSO) l 41.4 (t,
CH2), 62.5 (d, CHPh2), 121.7 (2×s, C arom.), 127.3
(2×d, C arom.), 127.3 (s, C arom.), 127.4 (2×d, C
arom.), 128.3 (4×d, C arom.), 128.8 (4×d, C arom.),
131.0 (2×d, C arom.), 131.4 (s, C arom.), 134.7 (2×d,
C arom.), 138.9 (2×s, C arom.), 163.3 [2×s, C(O)-N-
C(O)], 167.5 (s, C=O); IR (KBr) 3143 (OH), 2885,
4.2.2. 1,3-Dioxo-1H-benz[de]isoquinoline-2(3H)-acetyl
chloride. To a suspension of 1.25 g (4.88 mmol) of
1,3-dioxo-1H-benz[de]isoquinoline-2(3H)-acetic acid in
35 mL CH2Cl2 and three drops of DMF was added a
fivefold excess of oxalic chloride (2.15 mL, 3.17 g, 25.0
mmol) at ca. 20°C. The mixture was stirred for 4 h,
the solvent and excess oxalic chloride were removed
(20°C at 20 torr) and the solid, green residue was
recrystallized from CH2Cl2/petroleum ether (30–50°C).
The product was obtained as light brown powder in
–
1699 [–C(O)–N–C(O)–], 1663 [ C(O)–N–], 1615, 1454,
1380, 1239 cm−1; MS [m/z] (rel. intensity in%): 418
(M+−H2O, 7), 238 (19), 221 (25), 211 (20), 210 (55),
208 (58), 182 (100), 180 (32), 167 (37), 77 (27).
C27H18N2O3 (418.1) [M−H2O]+, HRMS (EI): Anal.
calcd 418.1317; found: 418.1319.
1
92% yield (1.23 g, 4.50 mmol); H NMR (200 MHz,
CDCl3) l 5.32 (s, 2H, CH2), 7.77 (t, J=8.0 Hz, 2H, H
arom.), 8.25 (dd, J=8.0 Hz, J=0.6 Hz, 2H, H arom.),
8.60 (dd, J=8.0 Hz, J=0.6 Hz, 2H, H arom.); 13C
NMR (63 MHz, d6-DMSO) l=41.2 (CH2), 121.4 (2×s,
C arom.), 129.0 (2×d, C arom.), 129.0 (s, C arom.),
131.1 (2×d, C arom.), 131.3 (s, C arom.), 134.8 (2×d,
C arom.), 164.7 (2×s, C(O)–N), 169.3 (s, C(O)-Cl); IR
(KBr) 2994, 2954, 1803 [C(O)Cl], 1725 and 1702 (–
CO–N–CO–), 1660, 1386, 1237, 968 cm−1. Anal. calcd
for C14H8ClNO3 (273.7): C, 61.44; H, 2.95; N, 5.12.
Found C, 61.77; H, 3.24; N, 5.16.
4.3. Preparation of the hydroxy-protected hydroperox-
ide TADOOMe, (4R,5R)-3d
4.3.1. [(4R,5R)-5-(Methoxydiphenylmethyl)-2,2-dimethyl-
1,3-dioxolan-4-yl]diphenyl-methanol (I). A suspension of
the TADDOL monochloride20 (3.86 g, 7.96 mmol) in
MeOH (60 mL) was treated with Et3N (1.20 mL, 8.61
mmol) and heated under reflux for 1.5 h. After cooling
to ca. 20°C, the suspension was filtered to yield analyt-
ically pure I (3.16 g, 83%) as white solid. Mp 165–
166°C, (lit.20b169.8–170.4°C); [h]rDt=−30.1 (c 1.35,
CHCl3), (lit.:20b [h]Drt=−27.0 (c 1.00, CHCl3); IR
(CHCl3) 3321, 3059, 2941, 1957, 1817, 1600, 1495,
1447s, 1381, 1372, 1168, 1087, 1048, 882, 641; 1H
NMR (300 MHz, CDCl3): 0.93 (s, Me), 1.03 (s, Me),
2.97 (s, OMe), 4.25 (d, J=8.1, CH), 4.59 (d, J=8.1,
CH), 6.35 (s, OH), 7.20–7.50 (m, 18 arom. H), 7.62–
7.65 (m, 2 arom. H); 13C NMR (75 MHz, CDCl3):
26.85, 27.06, 52.41 (Me); 77.24 (C); 79.30, 81.51 (CH);
84.75, 108.87 (C); 126.91, 127.07, 127.20, 127.64,
127.70, 127.88, 128.40, 128.66, 129.98 (CH); 137.11,
138.86, 143.85, 146.43 (C). MALDI-FT-ICR-MS:
503.2 (72, [M+Na]+), 413.2 (20, [M−OMe−OCMe2−1+
Na]+), 273.0 (100). HRMS calcd for [M+Na]+
(C32H32O4Na): 503.2193; found: 503.2191. Anal. calcd
for C32H32O4 (480.6): C 79.97, H 6.71; found: C, 79.94;
H, 6.63.
4.2.3. N-Hydroxy-a-phenylbenzenemethanamine19.
A
mixture of 2.96 g (15.0 mmol) benzophenone oxime
and 5.05 mL (4.65 g, 50 mmol) of the pyridine–borane
complex in 25 mL of ethanol was kept below 5°C. To
this solution was added dropwise 10% aqueous hydro-
chloric acid (50 mL) and the mixture was stirred for 15
min at room temperature (ca. 20°C). The solution was
made alkaline with sodium carbonate while cooling in
an ice-bath, and extracted with CHCl3 (3×120 mL).
The combined extracts were dried over MgSO4, and
after evaporation of the solvent (40°C at 110 torr), the
crude product was purified by silica-gel chromatogra-
phy with a 1:2 mixture of EtOAc and petroleum ether
(30–50°C) as eluent (TLC, Rf=0.48), to afford N-
hydroxy-a-phenylbenzenemethanamine as colorless
powder (1.37 g, 6.87 mmol, 46% yield); mp 77–78°C
4.3.2.
(4R,5R)-4-(Chlorodiphenylmethyl)-5-(methoxy-
1
(lit.:19b 80–81°C); H NMR (200 MHz, CDCl3) l 5.23
diphenylmethyl)-2,2-dimethyl-1,3-dioxolane II. A solu-
tion of I (2.50 g, 5.20 mmol) in CH2Cl2 (25 mL) was
treated with Et3N (1.10 mL, 7.80 mmol) and SOCl2
(0.50 mL, 6.87 mmol). The mixture was heated at
reflux under stirring for 1.5 h, whereby the color of the
(s, 1H, CHPh2), 5.52 (s, br, 2H, NH and OH), 7.21–
7.42 (m, 10H, H arom.); 13C NMR (63 MHz, CDCl3)
l 70.8 (NCH), 127.7 (2×d, C arom.), 127.9 (4×d, C
arom.), 128.7 (4×d, C arom.), 140.7 (2×s, C arom.).