m/z (rel. intensity) 473.3 (100, M + 1), 355.1 (70, [M − C9H12] +
1), 277.3 (40), 237.1 (30, [M − 2 × C9H12] + 1).
(d, 1H, J = 7.6 Hz), 4.7 (d, 1H, J = 12.8 Hz), 4.3 (d, 1H, J =
6.2 Hz), 4.1 (d, 1H, J = 13.0 Hz), 3.8 (d, 1H, J = 12.2 Hz), 3.65
(d, 1H, J = 12.6 Hz), 3.0 (q, 2H, J = 12.2 Hz), 2.34 (d, 3H, J =
6.6 Hz), 1.45 (d, 3H, J = 6.4 Hz); dC(100 MHz; CDCl3; Me4Si)
170.0 (CH), 141.5 (CIV, d, J = 6.4 Hz), 140.9 (CIV), 137.9 (CIV),
137.5 (CH), 136.4 (CIV), 136.0 (CIV), 134.4 (CIV), 133.6 (CIV), 133.0
(CH), 131.9 (CH), 131.8 (CIV), 131.6 (CH), 130.9 (CIV), 129.7 (CH),
129.1 (CH), 128.9 (CH), 127.9 (CH), 127.7 (CH), 127.3 (CH),
126.6 (CIV), 126.5 (CH), 126.2 (CH), 126.0 (CH), 125.9 (CH),
125.7 (CH), 124.7 (CH), 123.1 (CIV), 121.4 (CH), 114.2 (CIV, d,
J = 20.0 Hz), 68.1 (CH), 53.6 (CH2), 53.1 (CH2), 51.1 (CH2), 29.7
(CH2), 21.7 (CH), 18.6 (CH3), 14.2 (CH3); dP(162 MHz; CDCl3;
H3PO4) −80.99; MS-ES (+) m/z (rel. intensity) 575.3 (30), 543.7
(100, M+), 389.3 (60, M − C12H12), 235.3 (10, M − 2 × C12H12);
MS-ES (−) m/z (rel. intensity) 769.0 (100, TRISPHAT).
(S,M)-4d. This second eluted diastereomer was isolated using a
semi-preparative HPLC column (hexane–◦isopropanol 95 : 5). Rf
0.37 (benzene–diethyl ether 2 : 1); mp 89 C; [a]2D0 +51.0 (c 0.39,
MeOH); CD (c 1.0 × 10−5 M, MeOH) De (k) 19.3 (255); mmax/cm−1
2965, 2789, 1631, 1598, 1451, 1356, 1220, 1100; dH(400 MHz;
CDCl3; Me4Si) 7.52–7.31 (m, 16H), 3.81 (d, 4H, JAB = 12.4 Hz),
3.44 (dd, 2H, J = 9.6 and 3.5 Hz), 3.06 (d, 4H, JAB = 12.4 Hz),
2.04 (m, 2H), 1.74 (m, 2H), 0.69 (t, 6H, J = 7.6 Hz); dC(100 MHz;
CDCl3; Me4Si) 143.5, 140.3, 134.7, 129.0, 128.7, 128.3, 127.3,
126.9, 69.1, 53.0, 27.1, 10.3; MS-ES (+) m/z (rel. intensity) 473.3
(100, M), 355.1 (100, [M − C9H12] + 1), 237.3 (80, [M − 2 ×
C9H12] + 1).
Atropisomers 4e. Starting from 250 mg of biphenyl-2,2ꢀ,6,6ꢀ-
tetracarboxaldehyde, compound 4e was obtained as a mixture of
two diastereomers [58 : 42 ratio (S,M)/(S,P), 380 mg, 100%].
(S,M)-4e. This first eluted diastereomer was isolated by chro-
matography on silica gel using benzene as eluent and obtained
as a white solid (◦76 mg, 20%). Rf 0.91 (benzene–diethyl ether 1 :
1); mp 171–172 C; [a]2D0 +256.0 (c 0.41, CHCl3); CD (c 1.0 ×
10−5 M, MeOH) De (k) 16.4 (255); mmax/cm−1 2967, 2863, 1459,
1356, 1154, 1116; dH(400 MHz; CDCl3; Me4Si) 7.35 (m, 6H), 3.65
(d, 4H, JAB = 12.5 Hz), 3.48 (d, 4H, JAB = 12.5 Hz), 2.53 (q, 2H,
J = 7.0 Hz), 1.19 (d, 6H, J = 7.0 Hz), 0.99 (s, 18H); dC(100 MHz;
CDCl3; Me4Si) 139.6, 136.4, 128.9, 128.0, 68.2, 54.1, 27.0, 11.6;
MS-ES (+) m/z (rel. intensity) 405.7 (100, M + 1).
(S,P)-6d. Starting from (S,P)-4d (45 mg, 0.095 mmol), the
desired compound was obtained as a yellow solid (100 mg, 85%).
Rf 0.72 (CH2Cl2–MeOH 95 : 5, SiO2); mp 200 ◦C (decomp.); [a]2D0
−3552 (c 0.12, MeOH); mmax/cm−1 2934, 1640, 1593, 1562, 1445,
1389, 1301, 1235, 990, 819, 718, 669; dH(400 MHz; CDCl3; Me4Si)
9.85 (s, 1H), 7.81–7.1 (m, 13H), 6.3 (d, 1H, J = 7.5 Hz), 5.9 (t, 1H,
J = 7.2 Hz), 4.7 (d, 1H, J = 13.0 Hz), 4.3 (d, 1H, J = 13.2 Hz),
3.7 (dd, 2H, J = 25.0 and 37.9 Hz), 3.05 (t, 3H, J = 11.7 Hz), 2.55
(m, 3H), 2 (m, 1H), 1.65 (m, 2H), 1.15 (t, 3H, J = 7.2 Hz), 0.9 (m,
1H), 0.65 (t, 3H, J = 7.2 Hz); dC(100 MHz; CDCl3; Me4Si) 168.2
(CH), 142.7 (CIV), 141.9 (CIV), 141.5 (CIV, d, J = 6.4 Hz), 138.4
(CIV), 137.6 (CH), 136.5 (CIV), 136.0 (CIV), 133.4 (CH), 133.1 (CIV),
132.8 (CIV), 132.0 (CH), 130.4 (CH), 130.3 (CH), 129.3 (CH), 128.7
(CH), 128.6 (CH), 128.5 (CH), 127.9 (CH), 127.4 (CH), 127.0
(CH), 126.1 (CIV), 123.0 (CIV), 114.0 (CIV, d, J = 20.0 Hz), 68.7
(CH), 53.2 (CH2), 53.0 (CH2), 51.6 (CH2), 27.2 (CH2), 25.2 (CH),
23.9 (CH2), 11.0 (CH3), 10.1 (CH3); dP(162 MHz; CDCl3; H3PO4)
−80.97; MS-ES (−) m/z (rel. intensity) 768.5 (100, TRISPHAT);
MS-ES (+) m/z (rel. intensity) 471.5 (100, M+), 197.4 (20).
(S,P)-4e. This second eluted diastereomer was isolated by a
preparative chromatography on basic alumina using pentane–c-
hexane–ethyl acetate (50 : 50 : 1.2) as eluent and obtained as a pale
yellow viscous oil (22.8 mg, 6%). Rf 0.18 (c-hexane); [a]2D0 −100.0
(c 0.41, CHCl3); CD (c 1.0 × 10−5 M, MeOH) De (k) −11.4 (255);
mmax/cm−1 2949, 2902, 2865, 1637, 1480, 1548, 1355, 1154, 1114,
1074, 927; dH(400 MHz; CDCl3; Me4Si) 7.35 (m, 6H), 3.56 (dd,
8H, JAB = 12.0 Hz), 2.84 (q, 2H, J = 7.1 Hz), 1.19 (d, 6H, J =
7.0 Hz), 1.02 (s, 18H); dC(100 MHz; CDCl3; Me4Si) 139.6, 136.4,
128.1, 127.8, 69.8, 55.4, 27.4, 11.6; MS-ES (+) m/z (rel. intensity)
405.5 (100, M + 1), 321.5 (80, [M − C6H14] + 1), 237.1 (20, [M −
2 × C6H14] + 1).
(S,M)-6e. Starting from (S,M)-4e (20.0 mg, 0.050 mmol), the
desired compound was obtained as an orange solid (46 mg, 79%).
◦
Rf 0.42 (CH2Cl2, Al2O3 basic); mp 241.3 C; [a]2D0 −329.6 (c 0.1,
MeOH); mmax/cm−1 2959, 1634, 1591, 1559, 1446, 1388, 1302, 1235,
990, 819, 718, 669; dH(400 MHz; CDCl3; Me4Si) 8.80 (s, 1H), 7.82
(d, 1H, J = 7.8 Hz), 7.67–7.44 (m, 4H), 4.90 (d, 1H, J = 13.4 Hz),
4.12 (q, 1H, J = 6.8 Hz), 3.83 (d, 1H, J = 10.4 Hz), 3.79 (d, 1H,
J = 9.0 Hz), 3.64 (d, 1H, J = 12.5 Hz), 3.51 (d, 1H, J = 11.9 Hz),
3.25 (d, 1H, J = 13.1 Hz), 2.63 (q, 1H, J = 7.0 Hz), 1.75 (d,
3H, J = 7.1 Hz), 1.22 (d, 3H, J = 7.0 Hz), 1.12 (s, 9H), 1.01 (s,
9H); dP(162 MHz; CDCl3; H3PO4) −80.99; MS-ES (−) m/z (rel.
intensity) 768.7 (100, TRISPHAT); MS-ES (+) m/z (rel. intensity)
403.5 (100, M+), 197.5 (12).
General procedure for the synthesis of the iminium TRISPHAT
salts 6c–e
In a 50 mL round-bottomed flask equipped with a magnetic
stirring bar, diazepine 4c–e (0.25 mmol, 1.0 equiv.) was dissolved in
5 mL of CHCl3 and N-bromosuccinimide (0.32 mmol, 1.3 equiv.)
was added to the solution. The mixture was stirred at room
temperature for a few minutes (usually 5 min) then a solution
of [cinchonidinium][D-TRISPHAT] (0.275 mmol, 1.1 equiv.) in a
minimum amount of acetone was added. After 5 min of stirring
at room temperature the solvents were removed under reduced
pressure. The desired iminium salts 6c–e were recovered after
column chromatography (silica gel 60; CH2Cl2).
(S,P)-6e. Starting from (S,P)-4e (13 mg, 0.032 mmol), the
desired compound was obtained as a yellow solid (16.5 mg, 92%).
◦
Rf 0.65 (CH2Cl2–MeOH 9 : 1); mp 237.8 C; [a]2D0 −134.0 (c 0.1,
MeOH); mmax/cm−1 2963, 1633, 1591, 1559, 1447, 1389, 1302, 1260,
1235, 1096, 990, 819; dH(400 MHz; CDCl3; Me4Si) 9.28 (s, 1H),
7.91 (m, 1H), 7.78 (d, 1H, J = 7.5 Hz), 7.63 (m, 2H), 7.49 (d,
1H, J = 7.2 Hz), 7.31 (m, 1H), 4.83 (d, 1H, J = 13.3 Hz), 4.48
(d, 1H, J = 13.3 Hz) 4.21 (q, 1H, J = 7.0 Hz), 3.62 (m, 3H),
3.40 (d, 1H, J = 11.6 Hz), 2.91 (q, 1H, J = 7.1 Hz), 1.66 (d, 3H,
J = 7.0 Hz), 1.21 (s, 9H), 1.04 (m, 12 H); dP(162 MHz; CDCl3;
(S,P)-6c. Starting from (S,P)-4c (30 mg, 0.055 mmol), the
desired compound was obtained as a yellow solid (65 mg, 90%).
Mp 210.1 ◦C; [a]D20 −1588 (c 0.10, MeOH); mmax/cm−1 2928, 1692,
1640, 1594, 1448, 1390, 1302, 1236, 991, 823, 670; dH(400 MHz;
CDCl3; Me4Si) 10.5 (s, 1H), 8.4 (s, 1H), 8.3–6.5 (m, 20H), 5.45
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The Royal Society of Chemistry 2007
Org. Biomol. Chem., 2007, 5, 501–506 | 505
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