PAPER
Enantiotopic Discrimination on Achiral Substrates
3049
raphy (silica gel; hexanes–EtOAc, 9:1), a 35:65 inseparable mixture
of 2e and 3e.
3g
1H NMR (250 MHz, CDCl3): d = 1.60–1.85 (m, 6 H), 4.80 (d,
J = 11.7 Hz, 1 H), 5.12 (m, 1 H), 5.12 (d, J = 17.4 Hz, 1 H), 6.15 (t,
J = 4.8 Hz, 1 H), 6.25 (dd, J = 17.4, 11.7 Hz, 1 H), 7.71–7.88 (m,
4 H).
Yield: 84%; pale-yellow oil.
IR (neat): 2964, 2867, 1920, 1803, 1598 cm–1.
13C NMR (63 MHz, CDCl3): d = 20.1, 25.5, 29.4, 45.6, 110.9, 123.2,
2e
131.9, 132.5, 133.0, 137.2, 138.5, 168.5.
1H NMR (250 MHz, CDCl3): d = 1.37–1.47 (m, 2 H), 2.02–2.07 (m,
2 H), 2.16–2.22 (m, 2 H), 2.37 (m, 2 H), 2.45 (s, 3 H), 3.87 (dd,
J = 7.0, 5.7 Hz, 2 H), 5.73 (t, J = 7.0 Hz, 1 H), 7.32 (m, 2 H), 7.72
(d, J = 8.3 Hz, 2 H).
MS (EI): m/z (%) = 253 (1) [M+], 148 (100), 130 (34), 106 (95), 91
(71).
HRMS (ES): m/z calcd for C16H15NO3: 253.1103; found: 253.1098.
13C NMR (63 MHz, CDCl3): d = 20.4, 21.1, 21.6, 22.4, 59.7, 106.5,
128.5, 129.5, 136.5, 138.2, 143.0.
(1R)-N-2-Bicyclo[3.1.0]hex-6-ylethyl-1-phenylethenamine 2h1/
2h2 and [(1R)-1-Phenylethyl](2-vinylcyclohex-2-en-1-yl)amine
3h1 and 3h2
HRMS (EI): m/z calc for C15H18O2S: 262.1027; found: 262.1013.
The reaction using sodium (1R)-1-phenylethylamine as nucleophile
in THF at 20 °C for 12 h gave, after flash chromatography (silica
gel; hexanes–EtOAc, 9.5:0.5), a 31:69 mixture of inseparable dia-
stereomers 2h1 and 2h2 (ratio 68:32) and separable diastereomers
3h1 and 3h2 (ratio 40:60) in 80% overall yield. The ratio of the in-
separable diastereomers 2h1 and 2h2 was determined by HPLC
[Regis (S,S)-Whelk® 01] after amidation to the benzoyl derivatives.
When the reaction was carried out in DMSO at 80 °C for 12 h, only
the separable diastereomers 3h1 and 3h2 (ratio 46:54) were ob-
tained.
3e
1H NMR (250 MHz, CDCl3): d = 1.56–1.81 (m, 6 H), 2.46 (s, 3 H),
4.04 (d, J = 4.8 Hz, 1 H), 4.89 (d, J = 10.9 Hz, 1 H), 5.10 (d,
J = 17.5 Hz, 1 H), 6.17 (t, J = 3.9 Hz, 1 H), 6.24 (dd, J = 17.5, 10.9
Hz, 1 H), 7.32 (m, 2 H), 7.75 (d, J = 8.3 Hz, 2 H).
13C NMR (63 MHz, CDCl3): d = 16.8, 23.6, 24.7, 27.4, 61.2, 112.3,
124.2, 128.9, 129.1, 135.6, 137.6, 142.6, 144.4.
HRMS (EI): m/z calcd for C15H18O2S: 262.1027; found: 262.1008.
{2-Bicyclo[3.1.0]hex-6-ylidenethyl(diphenyl)phosphonio}(tri-
hydrido)borate (2f)
Diastereomers 2h1 and 2h2
Yield: 25% (THF, 20 °C); 0% (DMSO, 80 °C); colorless oil;
Rf = 0.1 (EtOAc).
1H NMR (360 MHz, CDCl3): d = 1.11–1.35 (m, 2 H), 1.39 (d,
J = 6.8 Hz, 6 H), 1.52–1.56 (m, 2 H), 1.70–1.90 (m, 12 H), 2.03–
2.28 (m, 2 H), 3.22–3.24 (m, 4 H), 3.86 (q, J = 6.8 Hz, 2 H), 5.82 (t,
J = 6.5 Hz, 2 H), 7.24–7.37 (m, 10 H).
The nucleophile was prepared at –78 °C by addition of n-BuLi (1.6
M in hexane, 0.32 mL) to a solution of diphenylphosphine borane
(100 mg, 0.5 mmol) in THF (2 mL) then allowed to warm to r.t. be-
fore addition of the p-allyl complex. After flash chromatography
(silica gel; hexanes–EtOAc, 9:1), the cyclopropylidene 2f was ob-
tained as the unique product.
13C NMR (90 MHz, CDCl3): d = 20.3, 20.5, 21.3, 24.1, 24.4, 29.5,
29.6, 48.6, 48.7, 57.3, 118.1, 118.3, 126.6, 126.8, 128.4, 131.8,
132.0, 145.7.
MS (EI): m/z (%) = 227 (2) [M+], 122 (16), 120 (16), 106 (22), 105
(100), 79 (22).
Yield: 130 mg (85%); pale-yellow oil.
IR (neat): 3369, 2953, 2862, 2381 cm–1.
1H NMR (250 MHz, CDCl3): d = 1.21–1.75 (m, 11 H), 3.14 (m,
2 H), 5.74 (q, J = 7.6 Hz, 1 H), 7.46 (m, 6 H), 7.67 (m, 4 H).
13C NMR (63 MHz, CDCl3): d = 20.5, 21.2, 29.6, 30.5, 109.5, 128.6,
128.7, 131.1, 131.2, 132.1, 132.2, 132.3, 137.0.
HRMS (ESI+): m/z calcd for C16H22N: 228.1747; found: 228.1752.
31P NMR (101 MHz, CDCl3): d = 16.0 (d, J = 69 Hz).
Diastereomer 3h1
HRMS (ES): m/z calcd for C20H24BPNa: 329.1606; found:
329.1601.
Yield: 22% (THF, 20 °C); 37% (DMSO, 80 °C); pale-yellow oil;
Rf = 0.8 (EtOAc); [a]D20 +50 (c 1.18, CHCl3).
IR (neat): 3435, 2959, 2863, 1641 cm–1.
2-(2-Bicyclo[3.1.0]hex-6-ylideneethyl)-1H-isoindole-1,3(2H)-di-
one (2g) and 2-(2-Vinylcyclohex-2-en-1-yl)-1H-isoindole-
1,3(2H)-dione (3g)
The reaction using potassium phthalimide as nucleophile, per-
formed in DMSO at 80 °C for 12 h gave, after flash chromatography
(silica gel; hexanes––EtOAc, 9:1), an 80:20 inseparable mixture of
2g and 3g.
1H NMR (250 MHz, CDCl3): d = 1.20–2.20 [m, 7 H including 1.36
(d, J = 6.9 Hz, 3 H)], 3.53 (m, 1 H), 3.92 (q, J = 6.9 Hz, 1 H), 5.00
(d, J = 11.0 Hz, 1 H), 5.31 (d, J = 17.5 Hz, 1 H), 5.81 (t, J = 4.0 Hz,
1 H), 6.29 (dd, J = 17.5, 11.0 Hz, 1 H), 7.20–7.43 (m, 5 H).
13C NMR (90 MHz, CDCl3): d = 16.5, 24.4, 25.9, 27.1, 50.2, 58.0,
110.1, 126.6, 126.7, 128.2, 131.8, 138.3, 138.9, 147.4.
MS (EI): m/z (%) = 227 (15) [M+], 120 (24), 106 (52), 105 (100), 79
(30), 77 (19).
Yield: 79%; pale-yellow oil.
IR (neat): 2977, 2863, 1772, 1713 cm–1.
Anal. Calcd for C16H21N (227.34): C, 84.53; H, 9.31. Found: C,
84.29; H, 9.28.
2g
1H NMR (250 MHz, CDCl3): d = 1.04–1.50 (m, 4 H), 2.05 (m, 2 H),
2.10–2.20 (m, 2 H), 4.39 (d, J = 5.4 Hz, 2 H), 5.84 (t, J = 5.4 Hz,
1 H), 7.71–7.88 (m, 4 H).
Diastereomer 3h2
Yield: 33% (THF, 20 °C); 44% (DMSO, 80 °C); pale-yellow oil;
Rf = 0.7 (EtOAc); [a]D20 +24 (c 1.31, CHCl3).
13C NMR (63 MHz, CDCl3): d = 20.0, 20.5, 21.2, 29.4, 38.8, 113.2,
123.2, 132.3, 133.7, 133.8, 168.1.
MS (EI): m/z (%) = 253 (4) [M+], 160 (61), 148 (83), 130 (36), 106
(100), 91 (71).
IR (neat): 3430, 2934, 2864, 1643 cm–1.
1H NMR (360 MHz, CDCl3): d = 0.85–2.30 [m, 7 H including 1.38
(d, J = 6.5 Hz, 3 H)], 3.18 (m, 1 H), 3.91 (q, J = 6.5 Hz, 1 H), 4.72
(d, J = 17.6 Hz, 1 H), 4.76 (d, J = 10.8 Hz, 1 H), 5.78 (t, J = 4.0 Hz,
1 H), 6.14 (dd, J = 17.6, 10.8 Hz, 1 H), 7.20–7.37 (m, 5 H).
HRMS (ES): m/z calcd for C16H15NO3: 253.1103; found: 253.1101.
Synthesis 2009, No. 18, 3047–3050 © Thieme Stuttgart · New York