Chiral Ligands in Grignard Reactions
957
69.4 (t, Ph-CH2-O-CH2), 65.8 (t, O-CH-O-CH2), 48.4 (d, C-4), 47.5 (s, C-7), 47.0 (s, C-8), 45.9 (d,
C-3a), 38.6 (t, C-3), 32.4 (t, C-6), 28.9 (t, C-5), 22.9, 20.4, and 11.6 (3q, 3 CH3) ppm.
(2R-(2ꢀ,3aꢀ,4ꢁ,7ꢁ,7aꢀ))-Octahydro-2-((2-(methoxy)phenyl)methoxy)-7,8,8-trimethyl-
4,7-methanobenzofuran (2c; C20H28O3)
Prepared analogously to 2b from 4.49 g (12.9 mmol) of (MBE)2O and 3.57 g (25.8 mmol) of 2-
methoxybenzenemethanol [14]; yield after VFC (220 g, PE/Et2O (50:1)) and Kugelrohr distillation:
4.75 g (58%) of 2c as a colorless oil.
25
D
1
B.p.: 80ꢀC/1.1 Pa (Kugelrohr); ꢀ ꢁ90:8 ꢂc 1, CH2Cl2); H NMR (200 MHz, ꢂ, CDCl3):
7.42±7.18, and 7.01±6.82 (2m, 4H, Ph-H), 5.25 (dd, 1H, 2-H), 4.71 and 4.51 (2d, J 13 Hz, 2 H, Ph-
CH2-O) 3.97 (d, J 6.6 Hz, 1H, 7a-H), 3.80 (s, 3H, OCH3), 2.4±0.8 (m, 17H, aliphatic H, therein:
1.01, 0.98, and 0.80 (3s; 9H, 3 CH3)) ppm; 13C NMR (50 MHz, ꢂ, CDCl3): 157.1 (s, C(ph)- 2), 128.7,
128.3 (2d, C(ph)-3, C(ph)-5), 127.1 (s, C(ph)-1), 120.3 (d, C(ph)-4), 110.2 (d, C(ph)-6), 104.5 (d, C-
2), 91.1 (d, C-7a), 63.2 (t, Ph-CH2-O), 55.3 (q, CH3-OPh), 48.5 (d, C-4), 47.6 (s, C-7), 47.0 (s, C-8),
46.0 (d, C-3a), 38.6 (t, C-3), 32.5 (t, C-6), 28.9 (t, C-5), 22.9, 20.5, and 11.6 (3q, 3 CH3) ppm.
General procedure of selectivity experiments
To a solution of 4 mmol of 2a±e in 18 ml of anhydrous Et2O and THF, resp., a solution of 4 mmol of
the organometallic compound (BuMgBr and BuLi, resp.) was added at 0ꢀC within 10 min. The
mixture was stirred for 30 min, cooled to ꢁ78ꢀC, a solution of 0.106 g (1 mmol) of benzaldehyde in
the corresponding solvent was added within 10 min, and the mixture was stirred for 1 h. After adding
5 ml of water the mixture was allowed to reach room temp. When THF was used as solvent, the
mixture was concentrated in vacuo and diluted with a mixture of Et2O and water. If BuMgBr was
used as organometallic component, ammonium chloride was added to dissolve the magnesium salts.
The aqueous phase was separated and extracted twice with Et2O. The combined organic layers were
dried with sodium sulfate, and the solvent was evaporated. VFC (20±30 g, PE/Et2O (50:1±4:1)) and
CC (150±300 g, PE/Et2O (20:1±4:1)), resp., yielded 1-phenyl-1-pentanol (4) and recovered 2a-e
which could be reused after Kugelrohr distillation. Additionally in experiments 5 and 6 (2b, BuLi,
THF) and 10 (2c, BuLi, THF) larger amounts (about 40%) of by-products were obtained which were
identi®ed as enolether 5, vinylacetal 6, and alcohol 7.
(3aS-(3aꢀ,4ꢁ,7ꢁ,7aꢀ))-3a,4,5,6,7,7a-Hexahydro-7,8,8-trimethyl-4,7-methanobenzofuran
(5; C12H18O)[15]
Colorless oil; 1H NMR (200 MHz, ꢂ, CDCl3): 6.10±6.02 (m, 1H, 2-H), 5.15±5.05 (m, 1H, 3-H), 4.35
(d, J 9.9 Hz, 1H, 7a-H), 2.86±2.74 (m, 1H, 3a-H), 1.8±0.75 (m, 14H, aliphatic H, therein: 1.11,
1.05, and 0.83 (3s, 9H, 3 CH3)) ppm; 13C NMR (50 MHz, ꢂ, CDCl3): 146.6 (d, C-2), 105.6 (d,C-3),
93.6 (d, C-7a), 52.5 (d, C-3a), 48.6 (d, C-4), 47.6 (s, C-7), 46.1 (s, C-8), 32.6 (t, C-6), 28.1 (t, C-5),
23.3, 18.9, and 11.2 (3q, 3 CH3) ppm; MS: m/z 178 [M ].
(2R-(2ꢀ,3aꢀ, 4ꢁ, 7ꢁ, 7aꢀ))-2-(Ethenyloxy)-octahydro-7,8,8-trimethyl-4,7-methanobenzofuran
(6; C14H22O2)
25
D
Colorless oil; ꢀ ꢁ103:3 ꢂc 1, CH2Cl2); 1H NMR (200 MHz, ꢂ, CDCl3): 6.43 (dd, J1 20 Hz,
J2 6.6 Hz, 1H, O-CH=CH2), 5.40 (dd, 1H, 2-H), 4.41 (d, J 20 Hz, 1H, O-CH=CH2 trans), 4.09 (d,
J 6.6 Hz, 1H, O-CH=CH2 cis), 3.98 (d, J 6.6 Hz, 1H, 7a-H), 2.4±0.75 (m, 17H, aliphatic H,
therein: 0.99, 0.96, and 0.80 (3s, 9H, 3 CH3)) ppm; 13C NMR (50 MHz, ꢂ, CDCl3): 148.9 (d, O-
CH=CH2), 104.7 (d, C-2), 91.8 (d, C-7a), 90.5 (t, O-CH=CH2), 48.4 (d, C-4), 47.6 (s, C-7), 47.0 (s,
C-8), 45.5 (d, C-3a), 38.3 (t, C-3), 32.3 (t, C-6), 28.8 (t, C-5), 22.9, 20.4, and 11.5 (3q, 3 CH3) ppm.