Stereoselective Radical Reactions
531 542
2.28 (brs, 1H), 2.24 2.17 (m, 2H), 2.20 (dd, 3J 7.2, 7.2 Hz, 1H), 2.01 (dm,
J 3.0 Hz, 1H), 1.86 (dd, 2J 14.5, 3J 7.3 Hz, 1H), 1.67 1.47 (m, 5H),
1.41 (s, 9H), 1.35 (dd, 2J 12.3, 3J 5.8 Hz, 1H), 1.24 (d, 2J 10.3 Hz, 1H),
39.4, 33.6, 32.8, 30.7, 30.5, 28.7, 28.1, 27.6, 27.5, 22.8, 16.1; IR (KBr): nÄ 3490,
2960, 1735, 1465, 1365, 1255, 1165, 1150, 1105, 1045, 920, 845, 760 cmÀ1
;
elemental analysis calcd (%) for C19H36O3 (312.3): C 73.03, H 11.61; found:
C 72.63, H 11.28.
2
3
2
1.18 (dd, J 9.0, J 6.3 Hz, 1H), 1.12 0.98 (m, 1H), 0.70 (dd, J 12.3,
3J 2.5 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 174.8, 80.7, 65.0, 45.5,
43.5, 40.4, 37.7, 37.2, 30.2, 30.2, 28.5, 28.1, 24.7; IR (KBr): nÄ 3310, 2950,
(1S*,2R*,4R*)- and (1R*,2S*,4R*)-3-(1-Hydroxymethyl-4-isopropyl-2-
methyl-cyclohexyl)-propionic acid tert-butyl ester (36):
1730, 1455, 1415, 1365, 1315, 1255, 1155, 1035, 945, 880, 850, 805, 765 cmÀ1
;
Table 7, entry 2: According to GP 2 35 (182 mg, 1.0 mmol), acrylic acid tert-
butylester (389 mg, 3.0 mmol), Cp2TiCl2 (25 mg, 0.1 mmol), zinc dust
(131 mg, 2.0 mmol), and collidine hydrochloride (394 mg, 2.5 mmol) in
THF (10 mL) for 15 h. Silica gel chromatography (CH:EE 5:1) gave 36
(240 mg, 77%) as 56:44 mixture of isomers. M.p. 808C; 1H NMR
(300 MHz, C6D6): d 3.42 (d, 2J 10.6 Hz, 1H), 3.33 (d, 2J 10.6 Hz,
1H), 3.24 (s, 1H)*, 2.20 (m, 4H), 2.19 (m, 2H), 1.72 (m, 3H), 1.57 (m, 3H),
1.40 (s, 9H)*, 1.38 (m, 2H), 1.37 (s, 9H), 1.22 (m, 2H), 0.98 (m, 8H), 0.86 (d,
3J 7.0 Hz, 3H), 0.82 (s, 9H), 0.82 (s, 9H)*, 0.78 (d, 3J 7.0 Hz, 3H)*;
13C NMR (75 MHz, C6D6): d 174.6, 174.5*, 80.4*, 80.2, 70.6*, 64.3, 49.1,
49.0*, 39.8, 39.6*, 39.1, 38.5*, 33.4, 33.0, 33.0*, 32.5, 32.1*, 31.0*, 30.8, 28.8*
28.7, 23.6*, 23.1, 23.0*, 17.1*, 17.1; IR (KBr): nÄ 3505, 2960, 2870, 1720,
1470, 1365, 1320, 1215, 1150, 1050, 980, 850, 760 cmÀ1; elemental analysis
calcd (%) for C19H36O3 (312.3): C 73.03, H 11.61; found: C 72.92, H 11.62.
elemental analysis calcd (%) for C15H26O3 (254.4): C 70.83, H 10.30; found:
C 70.85, H 10.32.
Conversion of 29 to 30: Hydroxyester 29 (50 mg, 0.2 mmol) and 10-
camphorsulfonic acid (9.3 mg, 0.04 mmol) were dissolved in CH2Cl2
(10 mL). After 19 h of stirring at room temperature and washing with
sat. aq. NaHCO3 (10 mL) and H2O (10 mL) the solvent was evaporated to
give pure 30 (23 mg, 64%). For spectral details see: Table 6, entry 7.
Table 6, entry 6: According to GP 2 28 (124 mg, 1.0 mmol), acrylic acid tert-
butylester (389 mg, 3.0 mmol), 18 (18 mg, 0.05 mmol), zinc dust (131 mg,
2.0 mmol) and collidine hydrochloride (394 mg, 2.5 mmol) in THF (10 mL)
for 15 h. Silica gel chromatography (PE:MTBE 4:1) gave 29 (130 mg,
51%).
5-Bicyclo[2.2.1]hepta-2-yliden-tetrahydropyran-2-on (30): Table 6, entry 7:
According to GP 2 28 (124 mg, 1.0 mmol) acrylonitrile (161 mg, 3.0 mmol),
Cp2TiCl2 (12.5 mg, 0.05 mmol), zinc dust (131 mg, 2.0 mmol), and collidine
hydrochloride (394 mg, 2.5 mmol) in THF (10 mL) for 19 and 5 h of reflux.
Aqueous layer re-extracted with EE (3 Â 20 mL). Silica gel chromatog-
raphy (CH/EE 2:1) gave 30 (161 mg, 89%). M.p. 39 418C; Rf (CH/EE
Table 7, entry 3: According to GP 2 35 (182 mg, 1.0 mmol), acrylic acid tert-
butylester (389 mg, 3.0 mmol), 18 (36 mg, 0.1 mmol), zinc dust (131 mg,
2.0 mmol) and hydrochloride (394 mg, 2.5 mmol) in THF (10 mL) for 15 h.
Silica gel chromatography (PE:MTBE 4:1) gave 36 (140 mg, 45%) as 48:52
mixture of diastereoisomers.
2:1) 0.41; 1H NMR (400 MHz, CDCl3): d AB-signal (dA1 4.11, dB1
9-tert-Butyl-7-methyl-2-oxa-spiro[5.5]undecan-3-one (37): Compound 36
(80 mg, 0.26 mmol) was added to a solution of camphorsulfonic acid
(51 mg, 0.22 mmol) and the mixture was stirred for 19 h at room temper-
ature. After washing with sat. aq. NaHCO3 (10 mL) and H2O(10 mL) the
organic phase was dried (MgSO4) and the solvent evaporated to yield 37
(50 mg, 82%). M.p. 598C; 1H NMR (300 MHz, C6D6): d 4.06 (d, 2J 11.3,
3J 5.0 Hz, 1H), 3.88 (d, 2J 11.3 Hz, 1H), 2.51 (t, 3J 7.5 Hz, 2H), 1.82
4.06, JAB 11.2 Hz, 2H), 2.55 (t, 3J 7.1 Hz, 2H), 2.26 (dd, 3J 3.5, 3.9 Hz,
1H), 2.04 (dm, 3J 3.2 Hz, 1H), 1.84 1.62 (m, 2H), AB-signal (dA2 1.80,
dB2 1.66, JAB ꢀ14.0 Hz, additionally split by 3J 7.0, 7.0 Hz, 2H), 1.59 (dd,
J 12.3, 3J 3.5 Hz, 1H), 1.53 (ddd, 2J 8.2, 3J 2.0, 2.0 Hz, 1H), 1.49 (dd,
3
2
2J ꢀ10.5, J 3.0 Hz, 1H), 1.42 (ddd, J ꢀ10.5, 3J 5.5, 4.2 Hz, 1H), 1.35
(ddd, 2J 12.6, 3J 4.0, 3.0 Hz, 1H), 1.25 (brd, 2J ꢀ9.0 Hz, 1H), 1.10 (ddd,
2J 12.0, 3J 6.0, 2.7 Hz, 1H), 1.09 (dd, 2J 12.3, 3J 2.7 Hz, 1H);
13C NMR (100 MHz, CDCl3): d 171.9, 75.7, 43.1, 41.9, 39.5, 37.5, 37.0,
33.0, 28.1, 27.4, 24.0; IR (KBr): nÄ 2945, 1730, 1465, 1390, 1350, 1295, 1240,
1205, 1180, 1065, 1035 cmÀ1; elemental analysis calcd (%) for C11H16O2
(180.2): C 73.30, H 8.95; found: C 73.06, H 8.72.
3
(m, 2H), 1.76 (m, 1H), 1.61 (m, 1H), 1.43 (brm, 2H), 1.40 (t, J 4.0 Hz,
2H), 1.21 (m, 1H), 1.08 (td, 2J 12.2, 3J 5.2 Hz, 1H), 0.97 (d, 3J 7.0 Hz,
3H), 0.78 (s, 9H); 13C NMR (75 MHz, C6D6): d 173.0, 41.2, 34.7, 33.8, 32.4,
29.9, 29.2, 29.0, 27.7, 27.4, 22.3, 11.1; IR (KBr): nÄ 2960, 2865, 1740, 1465,
1375, 1365, 1290, 1240, 1190, 1170, 1125, 1095, 1050, 1040, 1015, 990, 920,
880, 840, 735 cmÀ1; elemental analysis calcd (%) for C15H26O2 (238.2): C
75.58, H 10.99; found: C 75.30, H 11.06.
3-(2-endo-Hydroxymethyl-bicyclo[2.2.1]hept-5-ene-2exo-yl)-propionic
acid-tert-butylester (32):
Table 6, entry 8: According to GP 2 31 (122 mg, 1.0 mmol), acrylic acid tert-
butylester (389 mg, 3.0 mmol), Cp2TiCl2 (13 mg, 0.05 mmol), zinc dust
(131 mg, 2.0 mmol) and collidine hydrochloride (394 mg, 5.0 mmol) in THF
(10 mL) for 15 h. Silica gel chromatography (CH:EE 5:1) gave 32 (173 mg,
69%). M.p. 44 458C; Rf (80% CH, 20% EE) 0.24; 1H NMR (400 MHz,
C6D6): d 6.11 (d, 3J 3.0 Hz, 1H), 5.93 (dd, 3J 4.6, 3.3 Hz, 1H), 3.15
(brs, 1H), 2.59 (brs, 1H), 2.53 (brs, 1H), 2.32 (dd, 2J ꢀ15.0, 3J 7.8 Hz,
1H), 2.26 (dd, 2J 13.8, 3J 6.2 Hz, 1H), 2.19 (t, 3J 7.5 Hz, 1H), 2.17 (dd,
Acknowledgement
We are indebted to the Deutsche Forschungsgemeinschaft (Ga 619/1-2 and
Gerhard Hess-Programm), the Fonds der Chemischen Industrie (Dozen-
tenstipendium to A.G.) and the Alexander von Humboldt-Stiftung
(Forschungsstipendium to S.N.) for financial support.
3
2
2J 13.8, 3J 7.4 Hz, 1H), 2.14 (t, J 7.5 Hz, 1H), 1.76 (dd, J 14.1, 3J
7.3 Hz, 1H), 1.10 (dd, 2J 11.7, 3J 3.7 Hz, 1H), 0.92 (t, 3J 7.1 Hz, 1H),
0.50 (d, 2J 11.7 Hz, 1H); 13C NMR (100 MHz, C6D6): d 136.4, 136.0,
80.1, 66.3, 49.1, 47.7, 42.9, 35.0, 31.9, 31.4, 28.1; IR (KBr): nÄ 3295, 2970,
1725, 1445, 1365, 1310, 1160, 1025, 945, 850, 770, 720 cmÀ1; elemental
analysis calcd (%) for C15H24O3 (252.4): C 71.39, H 9.59; found: C 71.38, H
9.56.
[1] D. P. Curran, N. A. Porter, B. Giese, Stereochemistry of Radical
Reactions, VCH, Weinheim, 1996.
[2] a) B. Giese, Angew. Chem. 1989, 101, 993; Angew. Chem. Int. Ed. Engl.
1989, 28, 969; b) P. Renaud, M. Gerster, Angew. Chem. 1998, 110,
2704; Angew. Chem. Int. Ed. 1998, 37, 2562.
Conversion of 32 to 29: A mixture of 32 (90 mg, 0.36 mmol) and Pd/C
(10%, 30 mg) in methanol was stirred under a hydrogen atmosphere for 5 h
at room temperature. The solvent was removed under reduced pressure
and the crude product filtered through silica gel with pentane to yield 29
(85 mg, 94%).
[3] For recent reviews see: a) B. P. Roberts, Chem. Soc. Rev. 1999, 28, 35;
b) M. P. Sibi, N. A. Porter, Acc. Chem. Res. 1999, 32, 163; c) A.
Gans‰uer, H. Bluhm, Chem. Rev. 2000, 100, 2771; d) M. P. Sibi, in
Radicals in Organic Synthesis Vol.1 (Eds.: P. Renaud, M. P. Sibi),
Wiley-VCH, Weinheim, 2001, p. 461.
[4] a) A. Gans‰uer, T. Lauterbach, H. Bluhm, M. Noltemeyer, Angew.
Chem. 1999, 111, 3113; Angew. Chem. Int. Ed. 1999, 38, 2909; b) A.
Gans‰uer, H. Bluhm, T. Lauterbach, Adv. Synth. Catal. 2001, 343, 785.
[5] a) W. A. Nugent, T. V. RajanBabu, J. Am. Chem. Soc. 1988, 110, 8561;
b) T. V. RajanBabu, W. A. Nugent,J. Am. Chem. Soc. 1989, 111, 4525;
c) T. V. RajanBabu, W. A. Nugent, M. S. Beattie, J. Am. Chem. Soc.
1990, 112, 6408; d) T. V. RajanBabu, W. A. Nugent,J. Am. Chem. Soc.
1994, 116, 986.
(1S*,2S*,4R*)-3-(1-Hydroxymethyl-4-tert-butyl-2-methy-cyclohexyl)-pro-
pionic acid tert-butyl ester (34):
Table 7, entry 1: According to GP 2 33 (182 mg, 1.0 mmol), acrylic acid tert-
butylester (389 mg, 3.0 mmol), Cp2TiCl2 (25 mg, 0.1 mmol), zinc dust
(131 mg, 2.0 mmol) and hydrochloride (394 mg, 2.5 mmol) in THF (10 mL)
for 15 h. Silica gel chromatography (PE:MTBE 4:1) gave 34 (227 mg,
73%). 1H NMR (300 MHz, C6D6); d 3.24 (dd, 2J 11.3, 3J 5.0 Hz, 1H),
3.11 (dd, 2J 11.3, 3J 3.9 Hz, 1H), 2.30 (brm, 1H), 2.20 (t, 3J 7.6 Hz,
2H), 1.93 (t, 3J 7.7 Hz, 2H), 1.80 (brm, 1H), 1.45 (dd, 2J 12.8, 3J
4.3 Hz, 1H), 1.40 (m, 1H), 1.36 (s, 9H), 1.25 (m, 1H), 0.95 (d, 3J 7.2,
1H), 0.78 (s, 9H); 13C NMR (75 MHz, C6D6): d 175.0, 80.5, 67.4, 42.2,
[6] a) A. Gans‰uer, M. Pierobon, H. Bluhm, Angew. Chem. 1998, 110,
107; Angew. Chem. Int. Ed. 1998, 37, 101; b) A. Gans‰uer, H. Bluhm,
Chem. Eur. J. 2003, 9, No. 2
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