R. Annunziata et al. / Tetrahedron: Asymmetry 13 (2002) 2727–2734
2733
12.0, 4H), 2.43 (d, J=4.0 Hz, 2H), 1.90 (m, 2H),
Synthesis of 34: to a solution of benzoyl chloride (3
equiv.) and triethylamine (4 equiv.) in dry CH2Cl2 (5
ml) kept at 0°C under a nitrogen atmosphere, a solu-
tion of (R,R,S,S)-29 (1 equiv.) in 5 ml of dry CH2Cl2
was added. The reaction was kept at rt for 20 h, and
then quenched with H2O. The two phases were sepa-
rated, and the aqueous layers extracted twice with
CH2Cl2. Organic phases were dried over Na2SO4 and
filtered before removal of the solvent under reduced
pressure. The compound was purified by flash chro-
matography with hexanes/Et2O 50/50 as eluents (90%)
Found: C, 81.52; H, 6.49; N, 5.53; C34H32N2O2 requires
C, 81.57; H, 6.44; N, 5.60%; mp 228–230°C; [h]2D0=
+43.0° (c 0.360, CH2Cl2); w 1695 cm−1; 1H NMR: l=7.50–
7.15 (m, 20H), 5.51 (s, 2H), 3.80 (m, 2H), 1.78 (m, 4H),
1.53 (m, 4H); 13C NMR: l=173.9, 135.9, 133.4, 130.1,
129.1, 128.4, 127.3, 126.0, 65.45, 56.6, 32.1, 25.1.
1
1.87–1.00 (m, 20H). 13b: H NMR: l=7.40–7.20 (m,
10H), 3.67 (AB system, J=6.0, 4H), 2.10 (d, J=7.0 Hz,
2H), 1.92 (m, 2H), 1.87–1.00 (m, 20H).
Compounds 24a,b were purified with CH2Cl2/MeOH
95/5 as eluents. Found: C, 86.14; H, 7.19; N, 6.64;
C30H30N2 requires C, 86.08; H, 7.22; N, 6.69%. 24a:
1
[h]2D0=+152° (c 0.548, CH2Cl2); H NMR: l=7.33–7.20
(m, 16H), 3.90 (s, 2H), 3.75 (s, 4H), 2.32 ( s, 6H); 13C
NMR: l=130.8, 128.2, 128.0, 127.8, 126.7, 61.1, 51.05,
1
20.8. 24b: H NMR: l=7.38–7.10 (m, 16H), 3.96 (B
part of an AB system, J=13.5 Hz, 2H), 3.75 (m, 4H),
2.31 (s, 3H), 2.28 (s, 3H).
Compound 30 was purified with CH2Cl2/MeOH 95/5 as
eluents. Found: C, 73.15; H, 6.75; N, 8.53; C20H22N2F2
requires C, 73.08; H, 6.79; N, 8.61%; mp 85–88°C;
1
[h]2D0=−61.0° (c 0.384, CH2Cl2); H NMR: l=7.07 (dd,
Synthesis of 35: LiAlH4 (5 equiv.) was suspended in 20
ml of dry THF and kept under a nitrogen atmosphere.
(R,R,S,S)-34 dissolved in dry THF (10 ml) was added,
and the reaction mixture refluxed for 3.5 h, then
quenched with H2O (86.4 ml). Salts were filtered and
washed with Et2O; organics were then dried over
Na2SO4 and filtered before removal of the solvent
under reduced pressure. The compound was purified by
flash chromatography with hexanes/Et2O 50/50 as elu-
ents (64%). Found: C, 86.31; H, 7.72; N, 5.98;
C34H36N2 requires C, 86.40; H, 7.68; N, 5.93%; mp
J=5.5, 8.6 Hz, 4H), 6.83 (t, J=8.6 Hz, 4H), 3.77 (s,
2H), 2.65 (m, 2H), 1.78 (m, 4H), 1.43 (m, 4H); 13C
NMR: l=163.6, 160.3, 136.6, 129.6, 129.5, 114.8,
114.5, 113.3, 67.7, 61.3, 31.5, 24.75.
Compound 31: the compound was purified with CH2Cl2/
MeOH 95/5 as eluents. Found: C, 75.02; H, 7.97; N,
8.00; C22H28N2O2 requires C, 74.97; H, 8.01; N, 7.95%;
mp 108–125°C; [h]D20=−114.7° (c 0.204, CH2Cl2); 1H
NMR: l=7.08 (d, J=8.2 Hz, 4H), 7.00 (d, J=8.2 Hz,
4H), 3.84 (s, 2H), 3.73 (s, 6H), 2.67 (m, 2H), 1.78 (m,
4H), 1.43 (m, 4H); 13C NMR: l=158.7, 153.9, 129.3,
113.3, 67.1, 61.1, 55.05, 31.2, 24.65.
1
149–151°C; [h]2D0=−156.0° (c 0.442, CH2Cl2); H NMR:
l=7.23 (m, 12H), 6.98 (s, 8H), 3.85 (B part of an AB
system, J=16.5 Hz, 2H), 3.65 (s, 2H), 3.37 (A part of
an AB system, J=13.5 Hz, 2H), 3.00 (m, 2H), 1.60 (m,
2H), 1.27–1.07 (m, 4H); 13C NMR: l=141.6, 129.2,
127.6, 127.5, 127.4, 126.5, 125.7, 75.0, 67.9, 56.1, 31.7,
25.1.
Compound 32: the compound was purified with CH2Cl2/
MeOH 95/5 as eluents. Found: C, 74.01; H, 7.49; N,
8.67; C20H24N2O2 requires C, 74.05; H, 7.46; N, 8.64%;
mp 205–210°C; [h]D20=−20.5° (c 1.186, CH2Cl2); 1H
NMR: l=7.09 (dt, J=7.8, 1.6 Hz, 2H), 6.87 (d, J=7.8
Hz, 2H), 6.45 (dt, J=7.8, 1.0 Hz, 2H), 6.15 (dd,
J=7.8,1.6 Hz, 2H), 4.20 (s, 2H), 2.73 (m, 2H), 1.83 (m,
4H), 1.43(m, 4H); 13C NMR: l=156.8, 130.15, 129.0,
123.0, 118.65, 116.6, 63.3, 59.7, 31.4, 24.3.
Synthesis of 36: NaH (2.2 equiv.) was washed with
pentane and suspended in dry THF (10 ml) in a nitro-
gen atmosphere. A solution of (R,R,S,S)-29 (1 equiv.)
in dry THF (5 ml) was then added at rt. After 1 h,
phthaloyl chloride (1 equiv.) was added; the reaction
was refluxed for 27 h, and then quenched with satu-
rated aqueous NH4Cl. The two phases were separated,
and the aqueous layers extracted twice with Et2O and
twice with CH2Cl2. Organic phases were dried over
Na2SO4 and filtered before removal of the solvent
under reduced pressure. The compound was purified by
flash chromatography with CH2Cl2/MeOH 95/5 as elu-
ents (56%). Found: C, 79.67; H, 6.24; N, 6.59;
C28H26N2O2 requires C, 79.60; H, 6.20; N, 6.63%; mp
>250°C; [h]2D0=+248.0° (c 0.364, CH2Cl2); w 1695 cm−1;
1H NMR: l=7.65 (bs, 4H), 7.30 (bs, 8H), 7.03 (bs,
2H), 6.65 (bs, 2H), 6.07 (bs, 2H), 3.37 (bs, 2H), 1.86 (m,
2H), 1.33–1.13 (m, 6H); 13C NMR: l=171.1, 139.8,
128.9, 127.1, 126.1, 124.1, 59.0, 33.5, 24.4.
Synthesis of 33: NaH (2.2 equiv.) was washed with
pentane and suspended in dry THF (10 ml) in a nitro-
gen atmosphere. A solution of (R,R,S,S)-29 (1 equiv.)
in dry THF (5 ml) was then added at rt. After 1 h, allyl
bromide (3.3 equiv.) was added dropwise; the reaction
was refluxed for 27 h and then quenched with saturated
aqueous NH4Cl. The two phases were separated, and
the aqueous layers extracted twice with Et2O and twice
with CH2Cl2. Organic phases were dried over Na2SO4
and filtered before removal of the solvent under
reduced pressure. The compound was purified by flash
chromatography with hexanes/Et2O 50/50 as eluents
(52%). Found: C, 83.78; H, 8.64; N, 7.57; C26H32N2
requires C, 83.82; H, 8.66; N, 7.52%; mp 110–116°C;
[h]2D0=−73.8° (c 0.336, CH2Cl2); 1H NMR: l=7.07–
6.93 (m, 10H), 5.91 (m, 2H), 5.07 (dd, J=10.5, 1.2 Hz,
2H), 4.90 (dd, J=17.2, 1.4 Hz, 2H), 3.63 (s, 2H), 3.33
(B part of an AB system, J=16.0, 6.3 Hz, 2H), 2.91 (A
part of an AB system, J=16.0, 6.8 Hz, 2H), 2.54 (bd,
J=8.5 Hz, 2H), 2.27 (d, J=8.5 Hz, 2H), 1.80 (m, 2H),
1.32 (m, 4H).
Acknowledgements
We thank Sara Nemfardi and Andrea Tam for their
helpful collaboration. Partial financial support by
MIUR and CNR-ISTM is gratefully acknowledged.