Polymer-Grafted Ti-TADDOL Complexes
J . Org. Chem., Vol. 62, No. 10, 1997 3133
112.9, 116.9, 118.7, 124-141 (19 peaks), 155.6. MS (FAB,
m/ z) 643 (M+ + 1), 642 (M+). Anal. Calcd for C43H46O5: C,
80.3; H, 7.2. Found: C, 79.9; H, 7.5.
for 24 h. After cooling, a saturated solution of NH4Cl was
added until neutralization. The resulting solution was ex-
tracted with EtOAc, and the organic phase was dried (anhyd
MgSO4) and vacuum evaporated. The crude product was
purified by column chromatography (SiO2) using hexanes/
EtOAc (10/1) as the eluent. Yield: 400 mg, 29%. Mp 80-85
°C. [R]25D: +35 (c 0.011, THF). IR 3560, 1608, 1497, 1174,
1026. 1H NMR 4.95 (s, 2 H), 5.23 (d, 1 H), 5.41 (d, 1 H), 5.17
(s, 1 H), 6.8-7.7 (m, 29 H). 13C NMR 70.1, 78.7, 78.8, 81.0,
81.8, 104.9, 113.1, 116.1, 119.5, 127.0, 127.2, 127.3, 127.5,
127.7, 127.8, 128.1, 128.3, 128.4, 128.7, 129.6, 137.0, 138.8,
143.2, 144.4, 144.5, 146.2, 158.9. Anal. Calcd for
TADDOL 17c. Prepared from ketal 14 (1.5 g, 5.3 mmol)
and 2-naphthylmagnesium bromide (70 mmol), obtained from
2-bromonaphthalene (14.3 g, 70 mmol) and Mg (1.5 g, 70
mmol). Purified by column chromatography as for 17b.
Yield: 1.8 g, 25%. Mp 165-173 °C. [R]25D: +137 (c 0.006,
THF), IR 3391, 1178, 1122, 1103. 1H NMR 3.4 (s, 1 H), 4.6 (s,
1 H), 5.6 (d, 1 H), 5.8 (d, 1 H), 5.9 (s, 1 H) 6.5-8.5 (m, 33 H).
13C NMR 79.4, 80.4, 81.4, 81.6, 105.6, 113.2, 116.5, 118.6,
124.6, 124.8, 125.0, 125.1, 126-129 (13 peaks), 129.8, 132-
133 (6 peaks), 139.2, 140.6, 141.4, 141.7, 141.9, 142.2, 156.2.
MS (EI, m/ z) 730 (M+). Anal. Calcd for C51H38O5 2H2O: C,
79.9, H, 5.5. Found: C, 80.2; H, 5.7.
TADDOL 17d . Prepared from ketal 14 (13 g, 4.6 mmol)
and (p-methoxyphenyl)magnesium bromide (70 mmol), ob-
tained from 1-bromo-4-methoxybenzene (13.4 g, 70 mmol) and
Mg (1.5 g, 70 mmol). Purified by column chromatography as
for 17b. Yield: 1.3 g, 44%. Mp 113-118 °C. [R]25D: +25 (c
0.012, THF). IR 3538, 3383, 1177, 1098. 1H NMR 2.35 (s, 1
H), 3.24 (s, 1 H), 3.74 (s, 3 H), 3.77 (s, 3 H), 3.79 (s, 3 H), 3.81
(s, 3 H), 4.96 (s, 1 H), 5.07 (d, 1 H), 5.21 (d, 1 H), 5.29 (s, 1 H),
6.5-7.5 (m, 20 H). 13C NMR 55.2, 55.3, 78.1, 78.6, 81.1, 82.0,
104.7, 113.1, 113.3, 113.5, 113.8, 116.5, 118.8, 128.2, 128.4,
129.3, 129.5, 129.6, 135.9, 136.6, 136.6, 138.2, 138.9, 156.0,
158.4, 158.5, 158.8. MS (EI, m/ z) 650 (M+). Anal. Calcd for
C39H38O9: C, 72.0; H, 5.9. Found: C, 71.5; H, 6.1.
TADDOL 18a . Prepared from ketal 16 (5.5 g, 19 mmol)
and PhMgBr (0.56 mol) obtained from bromobenzene (29.4 mL,
0.56 mol) and Mg (13.5 g, 0.56 mol). Purified by column
chromatography (SiO2) with hexanes/EtOAc (80:20) as the
eluent to give 18a as a white solid. Yield: 1.55 g, 15%. Mp
110-115 °C. [R]25D: +53.67 (c 0.0086, THF). IR 3550, 3316,
1241, 1169, 1043. 1H NMR 1.33 (s, 3 H), 2.40 (s, 1 H), 2.64 (s,
1 H), 5.12 (d, 1 H), 5.18 (d, 1 H), 5.48 (s, 1 H), 6.7 (d, 2 H),
7.0-7.6 (m, 22 H). 13C NMR 30.1, 78.5, 79.2, 81.7, 83.3, 111.5,
115.3, 126-128 (several peaks), 137.3, 143.2, 143.5, 145.1,
145.2, 155.5. MS (EI, m/ z) 544 (M+). Anal. Calcd for
C36H32O5.H2O: C, 76.9; H, 5.9. Found: C, 76, 6; H, 6.0.
TADDOL 18b. Prepared from ketal 16 (3.55 g, 12 mmol)
and (p-methoxyphenyl)magnesium bromide (0.1 mol) prepared
from 1-bromo-4-methoxybenzene (12.5 mL, 0.1 mol) and Mg
(2.5 g, 0.1 mol). Purified by column chromatography (SiO2)
with mixtures hexanes/EtOAc (100:0, 100:10, 100:20) as the
eluent, to give 18b as a white solid. Yield: 2.8 g, 35%. Mp
122.5 °C. [R]25D: +55.37 (c 0.0051, THF). IR 3355, 1251, 1177,
1034. 1H NMR 1.41 (s, 3 H), 2.75 (s, 1 H), 2.87 (s, 1 H), 3.71
(s, 3 H), 3.76 (s, 6 H), 3.83 (s, 3 H), 5.04 (broad, 2 H), 5.7 (s, 1
H), 6.5-7.5 (m, 20 H). 13C NMR 30.2, 55.1, 78.2, 78.6, 81.9,
83.2, 111.2, 112.9, 113.4, 115.2, 126.4, 127.7, 128.2, 128.6,
129.4, 136.4, 137.3, 137.5, 155.5, 158.2, 158.3, 158.3, 158.6.
MS (EI, m/ z) 664 (M+). Anal. Calcd for C40H40O9‚H2O: C,-
70.4; H, 6.2. Found: C, 69.9; H, 6.0.
C
42H36O5.H2O: C,79.0; H, 6.0. Found: C, 78.7; H, 5.9.
TADDOL 26. Prepared from TADDOL 17b (300 mg, 0.45
mmol). Yield: 250 mg, 78%. Mp 103 °C. [R]25D: +75 (c 0.006,
THF). IR 3564, 1613, 1496, 1455, 1380, 1265, 1179, 1028, 814.
1H NMR (50 °C) 2.22 (s), 2.26 (s), 2.27 (s), 2.32 (s) (24 H), 4.97
(s, 2 H), 5.42 (s, 1 H), 5.65 (s, 1H), 6.5-8.0 (m, 21 H). 13C
NMR (50 °C) 20.8, 22.1, 79.8, 82.2, 112.9, 115.6, 118.9, 128-
137 (several overlapped peaks), 158.7. Anal. Calcd for
C
35H30O5: C,82.0; H, 7.1. Found: C, 81.8; H, 7.4.
Gen er a l P r oced u r e for th e P r ep a r a tion of P olym er
Su p p or ted Ti-TADDOL Com p lexes. A solution of TiCl4
(1 mL of a 1 M solution in toluene) and 1 mmol of Ti(OCHMe2)4
in 10 mL of dry toluene was stirred at -30°C for 30 min and
then at rt for 20 min. After this time the solution was diluted
with 10 mL of dry CCl4 and added to a suspension of the
corresponding polymer (19-24) in dry CCl4 (16 mL g-1 of
polymer). The amount of polymer depends on the degree of
functionalization and it is calculated to have 2 mmol of
TADDOL. The resulting mixture was heated under reflux for
24 h, and after this time the polymer was separated by
filtration and thoroughly washed with dry toluene. The
loading of titanium was determined by plasma emission
spectroscopy.
Gen er a l P r oced u r e for Diels-Ald er Rea ction s Usin g
Hom ogen eou s Ca ta lysts. A solution of TiCl4 (1 mL of a
solution 1 M in toluene) and 1 mmol of Ti(OCHMe2)4 in 6 mL
of dry toluene was stirred at -30°C for 30 min and then at rt
for 20 min. After this time a solution of 1 mmol of the
corresponding TADDOL (25, 26) in 20 mL of dry toluene, and
3.56 g of molecular sieves (4 Å) were added and stirring was
maintained for additional 60 min at 0°C. After this time a
solution of 3-crotonoyl-1,3-oxazolidin-2-one (1.395 g, 9 mmol)
in 30 mL of dry toluene, and freshly distilled cyclopentadiene
(7.92 g, 120 mmol) were added. The mixture was stirred for
24 h. Then 200 mL of 1 N HCl were added, and the mixture
was stirred for 15 min. The organic phase was filtered through
Celite, and the Celite was washed with 200 mL of 1 N HCl
and 200 mL of Et2O. The organic phase was separated and
dried over anhyd Na2SO4. The conversion was determined by
GC (FID, cross-linked methyl silicone column 25 m × 0.2 mm
× 0.33 µm, helium as carrier gas 18 psi, oven temperature
program 190°C (1 min), 5°C/min to 200°C (10 min), tR: 27 3.6
min, 28-31 7.7 min). The solvent was eliminated under
reduced pressure, and the conversion and endo/exo selectivity
were determined by 1H NMR integrating the signals corre-
sponding to the methyl group (exo cycloadducts 30 + 31 0.83
ppm, endo cycloadducts 28 + 29 1.10 ppm, 3-crotonoyl-1,3-
oxazolidin-2-one 1.94 ppm). The endo cycloadducts were
purified by column chromatography on silica gel using n-
hexane:EtOAc (2:1) as an eluent and the spectral data agree
with the previously described.19b The enantiomeric excess of
the endo cycloadducts was determined by 1H NMR in the
presence of Eu(hfc)3 (L/S molar ratio 0.3). Under these
conditions the signals corresponding to the vinyl protons of
the cycloadducts are split (Figure 4). The ee was confirmed
by polarimetry, and the mixture of endo cycloadducts coming
from the reaction promoted by the complex Ti-TADDOL 25
Gen er a l P r oced u r e for th e P r ep a r a tion of P olym er -
Su p p or ted TADDOLs 19-24. Obten tion of 19. A mixture
of TADDOL 17a (0.314 g, 0.6 mmol), NaH (24 mg, 0.6 mmol),
INBu4 (23 mg, 0.06 mmol), and a small amount of 18C6 in
dry THF (30 mL) were stirred at rt for 30 min. After that
period, a chloromethylated resin (1 mmol Cl/g, 1% DVB, 200
mg, 0.2 mmol) (C10H10)0.01(C8H8)0.88(C9H9Cl)0.11) was added, and
the suspension was refluxed for 48 h. The polymer was filtered
and washed with THF (3×), THF/H2O (1:1) (3×), THF/MeOH
(3×), MeOH (3×), CH2Cl2 (3×), and acetone (3×) to give resin
19 containing 0.69 mmol of functional group/g (DF ) 0.11,
100% conversion). IR 3557, 1179, 1155, 1108, 1029, 1017. 13
C
NMR (gel phase) 40.7, 69.9, 78.5, 80.8, 81.4, 104.8, 112.7,
115.6, 125-130, 143.0, 144.3. Anal. Calcd for (C10H10
)
-
0.01
(C8H8)0.88(C44H38O5)0.11: C, 88.0; H, 7.0. Found: C, 87.9; H,
7.1.
(Table 3, entry 5) gave [R]25 ) -62.8 (c 3.36, CCl4), which,
Gen er a l P r oced u r e for th e P r ep a r a tion of TADDOLs
25 a n d 26. Obten tion of 25. A mixture of TADDOL 17a
(1.5 g, 2.8 mmol), NaH (112 mg, 2.8 mmol), INBu4 (103 mg,
0.28 mmol), and a small amount of 18C6 in dry THF (30 mL)
were stirred at rt for 30 min. After that period, benzyl bromide
(0.34 mL, 2.8 mmol) was added, and the reaction was refluxed
D
taking into account the specific rotation of the pure enan-
tiomer,19b corresponds to a 33% ee of the 2S,3R-cycloadduct
28. This determination allowed us to assign the signals in
the 1H NMR spectrum to the corresponding enantiomers
(Figure 4).