Reductive Radical Cyclization of Cyanoketones
J . Org. Chem., Vol. 64, No. 9, 1999 3229
H, m), 7.00-7.65 (5 H, m); 13C NMR δ 16.8, 21.5, 25.47, 27.1,
27.5, 29.6, 43.7, 50.9, 76.3, 76.9, 84.0, 120.0, 125.0, 126.7, 128.3,
146.0. Anal. Calcd for C16H21NO: C, 78.97; H, 8.70; N, 5.76.
Found: C, 79.11; H, 9.04; N, 5.57.
Sp ectr a l d a ta for 13: oil (eluant, hexane-AcOEt, 5:1); IR
(neat) 3493 (OH), 1682 (CdO) cm-1; 1H NMR δ 1.00-3.10 (16
H, m), 7.00-8.10 (10 H, m); 13C NMR δ 21.5, 24.2, 27.6, 28.0,
29.5, 38.2, 43.6, 50.7, 80.0, 125.1, 126.5, 128.2, 128.3, 128.7,
133.0, 137.2, 146.3, 200.8. Anal. Calcd for C22H26O2: C, 81.95;
H, 8.13. Found: C, 81.84; H, 8.23.
Red u ctive Cycliza tion of 5e Usin g Cp 2Ti(P h )Cl/Zn /
Me3SiCl. To a solution of Cp2Ti(Ph)Cl (149 mg, 0.6 mmol) and
Zn (39 mg, 0.6 mmol) in dry degassed THF (7 mL) was added
Me3SiCl (0.11 mL, 0.9 mmol), and the solution was stirred for
1 h under Ar atmosphere at room temperature. To the
resultant green solution was added a solution of 9 (60 mg, 0.3
mmol) in dry degassed THF (5 mL) at room temperature, and
the reaction mixture was stirred for a further 2 h. The
standard workup as described above gave 11 (43 mg, 71%).
Cp2TiP h -Mediated Dou ble Cyclization of Dicyan odike-
ton e. According to the procedure for 7d -h , dicyanodiketone
14a (126 mg, 0.5 mmol) was cyclized to afford 96 mg of
tetracyclic R-hydroxyketone 15a (0.37 mmol, 75%) as a solid:
mp 171.5-172.0 °C (eluant, hexane-AcOEt 2:1); IR (CH2Cl2)
Sp ectr a l d a ta for 19: solid; mp 115.5-116.0 °C (eluant,
1
hexane-AcOEt 5:1); IR (CH2Cl2) 3586 (OH) cm-1; H NMR δ
0.66 (1 H, br s), 1.40 (3 H, s), 1.66-2.09 (6 H, m), 1.73 (1 H, br
s), 2.33 (1 H, q, J ) 6.6 Hz), 2.62 (1 H, ddd, J ) 15.3, 6.9, 4.5
Hz), 2.79 (1 H, ddd, J ) 15.3, 9.3, 4.8 Hz), 7.13-7.29 (3 H, m),
7.66 (1 H, dd, J ) 7.5, 1.5 Hz); 13C NMR δ 22.4, 27.7, 27.8,
27.9, 37.5, 48.9, 81.9, 83.8, 126.0, 126.8, 127.3, 128.1, 137.9,
140.9; MS (EI) m/z (rel intensity) 218 (M+, 98), 200 (85), 159
(63), 145 (100). Anal. Calcd for C14H18O2: C, 77.03; H, 8.31.
Found: C, 77.00; H, 8.34.
3530 (OH), 1744 (CdO) cm-1 1H NMR δ 1.71 (2 H, dt, J )
;
12.5, 7 Hz), 2.30 (1 H, dd, J ) 17, 1.5 Hz), 2.32 (1 H, dd, J )
16.5, 0.5 Hz), 2.57 (2 H, ddd, J ) 16.5, 12.5, 7 Hz), 2.64 (1 H,
dd, J ) 9.5, 0.5 Hz), 2.66 (1 H, dd, J ) 9.5, 1.5 Hz), 7.32-7.35
(2 H, m), 7.36-7.39 (2 H, m); 13C NMR δ 26.8, 35.3, 56.1, 87.2,
123.9, 130.5, 142.7, 216.0; MS (EI) m/z (rel intensity) 258 (M+,
85), 240 (82), 185 (93), 159 (100). Anal. Calcd for C15H14O4:
C, 69.76; H, 5.46. Found: C, 69.85; H, 5.37.
Sp ectr a l d a ta for 23: oil (eluant, hexane-AcOEt 2:1); IR
(neat) 3446 (OH), 2249 (CtN) cm-1; 1H NMR δ 1.20-1.80 (12
H, m), 1.90-2.25 (4 H, m), 2.46 (1 H, dd, J ) 16, 5 Hz) [minor
isomer δ 1.05-1.71 (8 H, m), 1.75 (1 H, m), 1.84-2.19 (3 H,
m), 2.22-2.51 (2 H, m)]; 13C NMR δ 16.4, 19.8, 20.7, 22.8, 23.5,
25.6, 27.4, 44.2, 46.9, 77.5, 119.5 [minor isomer δ 17.1, 22.9,
24.3, 27.3, 27.8, 30.0, 34.2, 39.3, 47.6, 80.1, 120.4]; MS (EI)
m/z (rel intensity) 179 (M+, 31), 162 (8), 111 (100). Anal. Calcd
for C11H17NO: C, 73.70; H, 9.56; N, 7.81. Found: C, 73.53; H,
9.73; N, 7.50.
In the same manner, 14b was converted into 15b: solid;
mp 122.5-123.8 °C (eluant, hexane-AcOEt 1:1); IR (CH2Cl2)
3550 (OH), 1742 (CdO) cm-1; 1H NMR δ 1.67 (4 H, m), 2.15 (2
H, m), 2.35-2.64 (6 H, m), 2.79 (2 H, br s); 13C NMR δ 26.2,
35.6, 35.8, 58.8, 86.8, 219.6; MS (EI) m/z (rel intensity) 210
(M+, 10), 192 (19), 182 (50), 137 (100). Anal. Calcd for
C11H14O4: C, 62.85; H, 6.71. Found: C, 62.75; H, 6.81.
Cp 2TiP h -Med ia ted Red u ctive Cycliza tion of 9 in th e
P r esen ce of i-P r OH. To the Cp2TiPh solution prepared as
above [Cp2TiCl2 (747 mg, 3.0 mmol)/toluene (10 mL) with
i-PrMgCl (3.3 mmol)/ether (5 mL) and PhMgBr (3.0 mmol)/
ether (5 mL)] was added a solution of cyanoketone 9 (199 mg,
1 mmol) in toluene (10 mL) and i-PrOH (10 mL) at room
temperature, and the reaction mixture was stirred for 2 h. The
standard workup as described above gave 11 (83 mg, 41%).
Ack n ow led gm en t. We gratefully acknowledge the
financial support (09750947 and 09305059) from the
Ministry of Education, Science, Sports and Culture,
J apanese Government.
J O982492S