S. D. Bull, M. G. Davidson et al.
FULL PAPERS
Table 4. Titanium triflate 6 catalyzed Diels–Alder reaction of (S)-4-benzyl-N-but-2-enoyloxazolidin-2-one 17
with cyclopentadiene 14.
under vacuum to afford the title com-
pound as a red/orange powder (6.05 g,
9.8 mmol, 98%); m.p.: (dec.) 285–
2878C (from hexane); n˜max =640, 860,
1029, 1160, 1243, 1416, 1477, 1685,
Entry
Catalyst
t [h]
Endo-18/endo-19/
Yield [%]
exo-major/exo-minor
1
2922 cmꢀ1; H NMR (300 MHz, CDCl3,
1
2
3
Titanium triflate 6
3
24
2
88:1:11:0
77:2:21:0
70:2:16:12
82
69
58
TiCl
N
ꢀ508C): d=2.14 (9H, s, ArCH3), 2.18
(9H, s, ArCH3), 3.09 (3H, J=10.6 Hz,
CHAHB), 4.04 (3H, J=10.6 Hz,
CHAHB), 6.70 (3H, s, ArH), 6.82 ppm
(3H, s, ArH); 13C NMR (75 MHz,
2,4-(dimethylphenoxy)3TiCl
CDCl3): d=16.1 (CH3), 21.1 (CH3), 59.3 (CH2), 123.4, 124.6, 128.9, 132.1,
133.1, 160.9 ppm (ArCO); 19F NMR (376 MHz): d=78.15 ppm; MS
(FAB): m/z 613.5 [M+]; elemental analysis: calcd (%) for
C28H30F3NO6STi: C 54.8, H 5.0, N 2.3; found: C 54.8; H 4.9; N 2.3;
C59.5H64F6N2O3S2Ti2, M=1273.04, red blocks, crystal size 0.20ꢅ0.22ꢅ
0.15 mm, triclinic, P-1, a=10.1340(2), b=16.8420(3), c=18.2010(4) ꢁ,
a=101.613(1), b=93.762(1), g=95.259(1)8, V=3018.8(1) ꢁ3, Z=2,
1cald =1.401 gcmꢀ3
, T=150(2) K, 41484 reflections measured, 10600
unique reflections (2q=25.038, Rint =0.0420) against 786 parameters gave
R1 =0.0436 and wR2 =0.1056 [I>2s(I)] (R1 =0.0630 and wR2 =0.1159 for
all data). CCDC 209585 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The Cam-
quest/cif.
Scheme 9. Titanium triflate 6 mediated syn-aldol reaction of N-acyl-oxa-
zolidin-2-one (S)-21.
General Procedure for Aza-Diels–Alder Reactions Catalyzed by Titanium
Triflate 6
Titanium triflate catalyst 6 (0.042 mmol) was added to a solution of Dani-
shefskyꢃs diene
4 (1.26 mmol) and the corresponding imine 3a–f
(0.42 mmol) in CH2Cl2 (1 mL) at room temperature. The mixture was
then stirred for 2 h before addition of silica (0.50 g) and removal of sol-
vent under vacuum. The crude reaction mixture was then purified using
column chromatography to afford the desired dihydropyridones 5a–f.
Scheme 10. Titanium triflate 6 catalyzed allylation and alkylation reac-
tions of benzaldehyde.
General Procedure for Diels–Alder Reactions Catalyzed by Titanium
Triflate 6
(ArCOH); MS (ES+) m/z calcd for C27H33NO3 [MꢀH]+, 420.2533;
found: 420.2531.
The relevant dienophile (0.5 mmol) and titanium triflate 6 (0.05 mmol)
were stirred together in CH2Cl2 (2 mL) at room temperature for 15 min.
The diene (1.5 mmol) was then added using a syringe and the reaction
mixture stirred at room temperature until no dienophile remained. The
reaction mixture was then filtered through a small plug of silica which
was washed with CH2Cl2 (2 mL), before the combined organic solvent
and excess diene were removed under vacuum to afford a crude product
that was purified by chromatography to afford the title compounds 11,
13a–b, 15a–c, 19.
Amine-(tris-phenolate) titanium iso-propoxide 2a[22]: Titanium tetra iso-
propoxide (6.2 mL, 20 mmol) was added to a suspension of amine-(tris-
phenol) 1a (8.4 g, 20 mmol) in toluene (50 mL) under a nitrogen atmos-
phere. The resulting yellow solution was heated to reflux and concentrat-
ed under vacuum to afford the title compound as a yellow powder (9.2 g,
17.6 mmol, 88%): m.p.: 193–1968C (from hexane); n˜max =862, 1160, 1362,
1379, 1476, 1607, 2853 cmꢀ1
d, J=6.0 Hz, OCH(CH3)2), 2.14 (9H, s, ArCH3), 2.17 (9H, s, ArCH3),
2.75 (3H, J=10.6 Hz, CHAHB) 3.90 (3H, J=10.6 Hz, CHAHB), 5.13 (1H,
hept, J=6.0 Hz, OCH(CH3)2), 6.62 (3H, s, ArH), 6.78 ppm (3H, s, ArH);
13C NMR (100 MHz, CDCl3): d=16.4 (ArCH3), 20.7 (ArCH3), 25.7 (CH-
(CH3)2), 58.6 (CH2) 79.8 (CH(CH3)2), 123.5, 124.1, 127.3, 129.1, 130.5,
;
1H NMR (400 MHz, CDCl3): d=1.45 (6H,
ACHTUNGTRENNUNG
Titanium Triflate 6 Mediated syn-Aldol Reaction
ACHTUNGTRENNUNG
(S)-4-Benzyl-3-propionyloxazolidin-2-one 20 (0.117 g, 0.5 mmol) and dii-
sopropylethylamine (0.9 mL, 0.53 mmol) were added to a solution of
(rac)-titanium triflate 6 (0.307 g, 0.5 mmol) in CH2Cl2 (3 mL) at 08C, and
the reaction stirred at 08C for one hour before benzaldehyde (0.5 mL,
0.5 mmol) was added. The reaction was allowed to warm to room tem-
perature and stirred for 48 h, before being filtered. The organic solvent
was removed to afford a crude product that was purified by chromatogra-
phy resulting in (S,S,S)-4-benzyl-3-(3-hydroxy-2-methyl-3-phenylpropa-
noyl)oxazolidin-2-one 21 (0.125 g, 0.36 mmol, 74% yield, 85% conver-
sion, ½aꢁ2D5 =+54 (c=1.3, CHCl3)) as a colourless oil.
A
ACHTUNGTRENNUNG
159.4 ppm (ArCO); MS (FAB): m/z 523.5 [M+], elemental analysis:
calcd (%) for C30H37NO4Ti: C 68.5, H 7.1, N 2.6; found: C 68.8, H 7.1,
N 2.7. Crystal data for C30H37N1O4Ti1, M=523.51, yellow blocks, crystal
size 0.25ꢅ0.22ꢅ0.17 mm, triclinic, P-1, a=13.0760(1), b=14.2000(2), c=
16.4720(3) ꢁ,
a=82.170(1),
b=88.758(1),
g=62.785(1)8,
V=
2691.70(7) ꢁ3, Z=4, 1cald =1.292 gcmꢀ3, T=150(2) K, 52968 reflections
measured, 12285 unique reflections (2q=27.518, Rint =0.0556) against 666
parameters gave R1 =0.0500 and wR2 =0.1181 [I>2s(I)] (R1 =0.0803 and
wR2 =0.1306 for all data). CCDC 209584 contains the supplementary
crystallographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre at
Titanium Triflate 6 Catalyzed Allylation Reaction
Benzaldehyde (0.1 mL, 1 mmol) and allyltributyltin (0.34 mL, 1.1 mmol)
were added to a solution of titanium triflate 6 (0.026 g, 0.05 mmol) in
CH2Cl2 (2 mL) at room temperature and the resultant solution stirred for
4 h before being quenched by addition of 1.0n HCl (4 mL). The organic
layer was washed with water before being dried over MgSO4 and the sol-
vent removed under vacuum to afford a crude product that was purified
by chromatography to afford 1-phenylbut-3-en-1-ol 22 (0.094 g,
0.64 mmol, 64%) as a yellow oil.
Amine-(tris-phenolate) titanium triflate 6[22]: Amine-(tris-phenolate) tita-
nium iso-propoxide 2a (5.23 g, 10 mmol) in toluene was treated with tri-
methylsilyl triflate (1.8 mL, 10 mmol), under a nitrogen atmosphere. The
resulting red suspension was heated to reflux for six hours and concen-
trated under vacuum which gave a red/orange solid that was suspended
in hexane and filtered. The residue was washed with hexane and dried
618
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2010, 5, 612 – 620