organocatalytic enantioselective desymmetrization of ... · (esi) m/z : 353 [m+na]+; melting point:...
TRANSCRIPT
1
Organocatalytic Enantioselective Desymmetrization of Cyclic
Enones via Phosphine Promoted [3+2] Annulations
Nathalie Pinto, Pascal Retailleau, Arnaud Voituriez and Angela Marinetti*
Institut de Chimie des Substances Naturelles
CNRS UPR 2301, Centre de Recherche de Gif
1 av. de la Terrasse, 91198 Gif sur Yvette, France
Table of Contents :
1) General methods
2) Substrates
3) Phosphine promoted [3+2] cyclisations on enones 1.
4) NMRspectra and HPLC analysis
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
2
1) General methods
All reactions were run under argon by using standard techniques for manipulating air-
sensitive compounds. Anhydrous solvents were obtained by filtration through drying columns
(THF, Et2O, CH2Cl2). All reagents were of commercial quality and were used without further
purification. Flash column chromatography was performed using 40-63 mesh silica. Nuclear
magnetic resonance spectra (1H, 13C, 31P) were recorded either on Brucker AV 500 or AV 300
spectrometers. IR spectra were recorded with a Perkin-Elmer FT-IR spectrophotometer. High
resolution mass spectra (HRMS-ESI) were obtained on LCT Waters equipment. Optical
rotations were determined with a JASCO P-1010 polarimeter. HPLC was performed at a
column temperature of 30°C on a Waters 2695 Separations Module equipped with a diode
array UV detector. Data are reported as follows: column type, eluent, flow rate, retention
time.
2) Substrates
4-methylcyclohexanone, 4-tert-butylcyclohexanone, 4-phenylcyclohexanone and 4-
isopropylcyclohexanone are commercially available. The diarylidenecyclohexanones
1a,c,d,f,e are known compounds. 1 , 2 They have been prepared as shown hereafter. 2,4-
dibenzylidenebicyclo[3.1.0]hexan-3-one 4a and 2,4-dibenzylidene-6-
methylbicyclo[3.1.0]hexan-3-one 4b were prepared according to literature procedure.3
(2E,6E)-2,6-dibenzylidene-4-methylcyclohexanone 1a. Method
A: 4-methylcyclohexanone (10 mmol, 1.12 g) was dissolved in
a mixture of ethanol (20 mL) and water (10 mL).
Benzaldehyde (20 mmol, 2 mL) and NaOH [1M] (10 mL) were
then added at 0°C. The mixture was stirred at room temperature overnight. The yellow
precipitate was filtrated and the desired compound was obtained as a yellow solid (2.27 g,
79%). 1H NMR (500 MHz, CDCl3) δ 7.81 (bs, 2H, C=CHC6H5), 7.50-7.25 (m, 10H), 3.07
1 Frey, H. Synthesis 1992, 387-390. 2 Dimmock, J. R.; Padmanilayam, M. P.; Zello, G. A.; Nienaber, K. H.; Allen, T. M.; Santos, C. L.; De Clercq, E.; Balzarini, J.; Manavathu E. K. ; Stables, J. P. Eur. J. Med. Chem., 2003, 38, 169-177 3 Kearley, M. L.; Lahti, P. M. Tetrahedron Lett.1991, 32, 5869-5872 ; Kearley, M. L.; Ichimura, A. S.; Lahti, P. M. J. Am. Chem. Soc. 1995, 117, 5235-5244; Flaugh, M. E.; Crowell, T. A.; Farlow, D. S. J. Org. Chem. 1980, 45, 5399-5400.
O
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
3
(dd, 2JAB = 16.0, 3J = 3.5 Hz, 2H, CHH), 2.52 (m, 2H, 2CHH), 1.89 (m, 1H, CHCH3), 1.08 (d, 3J = 6.5 Hz, 3H, CHCH3); 13C NMR (75 MHz, CDCl3) δ 190.3 (Cq), 137.3 (C=CHC6H5),
136.1 (Cq), 135.5 (Cq), 130.5 (CH), 128.7 (CH), 128.5 (CH), 36.6 (CH2), 29.6 (CHCH3), 21.8
(CHCH3); IR: νmax= 2957, 1660, 1603, 1568, 1444, 1288, 1240, 1142, 931, 770, 755, 692 cm-
1; MS (ESI) m/z : 289 [M+H]+; Melting point: 96-97°C.
(2E,6E)-2,6-dibenzylidene-4-isopropylcyclohexanone 1b.
Method A was employed, starting from 4-isopropyl-
cyclohexanone (1.6 mmol, 0.25 mL) and benzaldehyde (3.2
mmol, 0.35 mL). The product was obtained as a yellow solid
(330 mg, 65%). 1H NMR (500 MHz, CDCl3) δ 7.8 (br, 2H), 7.50-7.30 (m, 10H), 3.06 (dd, J =
15.5, 3.0 Hz, 2H, CH2), 2.60-2.55 (m, 2H, CH2), 1.64 (m, J = 6.5 Hz, 1H, CH), 1.60-1.50 (m,
1H, CH), 0.91 (d, 3J = 7.0 Hz, 6H, CH3); 13C NMR (75 MHz, CDCl3) δ 190.7 (Cq), 137.3
(C6H5CH=C), 136.2 (Cq), 135.8 (Cq), 130.5 (CH), 128.7 (CH), 128.6 (CH), 40.4 (CH), 31.7
(CH), 31.6 (CH2), 19.9 (CH3); IR: νmax= 1661, 1570, 1444, 1291, 1154, 775, 693 cm-1; MS
(ESI) m/z : 339 [M+Na]+; Melting point: 102-103°C.
(2E,6E)-2,6-dibenzylidene-4-tert-butylcyclohexanone 1c. Method
A: 4-tert-butylcyclohexanone (10 mmol, 1.54 g), was dissolved
in a mixture of ethanol (20 mL) and water (10 mL).
Benzaldehyde (20 mmol, 2 mL) and NaOH [1M] (10 mL) were
then added and the resulting mixture was heated at 50°C and stirred overnight. The yellow
precipitate was filtrated and the desired compound was obtained as a yellow solid after
crystallization in ethanol (1.79 g, 54%). 1H NMR (500 MHz, CDCl3) δ 7.80-7.75 (m, 2H),
7.50-7.30 (m, 10H), 3.17 (dd, J = 15.5, 2.0 Hz, 2H, CH2), 2.50-2.40 (m, 2H, CH2), 1.49 (m,
1H, CH), 0.95 (s, 9H, CH3); 13C NMR (75 MHz, CDCl3) δ 190.8 (Cq), 137.0 (CH), 136.3
(Cq), 136.2 (Cq), 130.4 (CH), 128.7 (CH), 128.6 (CH), 44.5 (CH), 32.7 (Cq), 29.7 (CH2),
27.4 (CH3); IR: νmax= 2959, 1660, 1603, 1445, 1244, 1157, 983, 776, 693 cm-1; MS
(ESI) m/z : 353 [M+Na]+; Melting point: 137-138°C.
(2E,6E)-2,6-dibenzylidene-4-phenylcyclohexanone 1d.
Method A was employed starting from 4-phenylcyclohexanone
(2.87 mmol, 500 mg) and benzaldehyde (5.74 mmol, 0.9 mL).
The product was obtained as a yellow solid from the crude
O
O
O
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
4
reaction mixture by filtration (958 mg, 96%). 1H NMR (500 MHz, CDCl3) δ 7.90-7.85 (m,
2H), 7.45-7.25 (m, 15H), 3.35-3.30 (m, 2H), 3.10-3.00 (m, 3H); 13C NMR (75 MHz, CDCl3)
δ 189.7 (Cq), 144.8 (Cq), 138.0 (CH), 135.9 (Cq), 135.2 (Cq), 130.6 (CH), 128.89 (CH),
128.87 (CH), 128.6 (CH), 126.99 (CH), 126.97 (CH), 41.0 (CH), 36.1 (CH2); IR: νmax= 1733,
1660, 1598, 1443, 1288, 1146, 983, 750 691 cm-1; MS (ESI) m/z : 373 [M+Na]+;Melting
point: 134-135°C.
(2E,6E)-4-tert-butyl-2,6-bis(4-methoxybenzylidene)
cyclohexanone 1e. Method A was employed starting
from 4-tert-butylcyclohexanone (10 mmol, 1.54 g)
and 4-methoxybenzaldehyde (20 mmol, 2.4 mL).
The product was obtained as a yellow solid (2.42 g,
62%). 1H NMR (500 MHz, CDCl3) δ 7.73 (m, 2H), 7.45 (d, J = 8.5 Hz, 4H), 6.95 (d, J = 8.5
Hz, 4H), 3.85 (s, 6H, OMe), 3.15 (dd, J = 15.5, 2.5 Hz, 2H, CH2), 2.44 (t, J ~ 14 Hz, 2H),
1.48 (tt, J = 13.0, 3.0 Hz, 1H), 0.97 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 190.5 (Cq), 160.0
(2Cq), 136.5 (CH), 134.4 (Cq), 132.3 (CH), 128.9 (Cq), 114.1 (CH), 55.4 (OCH3), 44.5 (Cq),
32.6 (Cq), 29.7 (CH2), 27.5 (CH3); IR: νmax= 2951, 1664, 1507, 1291, 1254, 1169, 1029, 830,
770 cm-1; MS (ESI) m/z : 413 [M+Na]+; Melting point: 171-172°C.
(2E,6E)-4-tert-butyl-2,6-bis(4-methylbenzylidene)cyclo-
hexanone 1f. Method A was employed with 4-tert-
butylcyclohexanone (10 mmol, 1.54 g) and 4-
methylbenzaldehyde (20 mmol, 2.35 mL)). The product
was obtained as a yellow solid (3.10 g, 87%). 1H NMR (500 MHz, CDCl3) δ 7.78 (m, 2H),
7.41 (d, J = 7.5 Hz, 4H), 7.25 (d, J = 7.5 Hz, 4H), 3.19 (d, J = 15.0 Hz, 2H), 2.46 (t, J ~ 14
Hz, 2H), 2.41 (s, 6H), 1.51 (t, J = 12.5 Hz, 1H), 0.99 (s, 9H); 13C NMR (75 MHz, CDCl3) δ
190.7 (Cq), 138.9 (Cq), 136.9 (CH), 135.6 (Cq), 133.4 (Cq), 130.5 (CH), 129.3 (CH), 44.5
(CH), 32.7 (Cq), 29.7 (CH2), 27.4 (C(CH3)3), 21.5 (CH3); IR: νmax= 2961, 2358, 1663, 1573,
1315, 1174, 930, 817, 666 cm-1; MS (ESI) m/z : 381 [M+Na]+; Melting point: 156-157°C.
(2E,6E)-4-tert-butyl-2,6-bis(4-chlorobenzylidene)cyclo-
hexanone 1g. Method A was employed starting from 4-
tert-butylcyclohexanone (10 mmol, 1.54 g) and 4-
chlorobenzaldehyde (20 mmol, 2.8 g). The product was
obtained as a yellow solid (3.25 g, 82%). 1H NMR (500 MHz, CDCl3) δ 7.65 (bs, 2H), 7.39
O
O
MeO OMe
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
5
(bs, 8H), 3.09 (m, 2H), 2.41 (m, 2H), 1.47 (m, 1H), 0.94 (s, 9H); 13C NMR (75 MHz, CDCl3)
δ 190.2 (Cq), 136.6 (Cq), 135.8 (CH), 134.7 (Cq), 134.5 (Cq), 131.6 (CH), 128.9 (CH), 44.5
(CH), 32.7 (Cq), 29.6 (CH2), 27.4 (CH3); IR: νmax= 2958, 1663, 1577, 1558, 1404, 1241,
1092, 983, 928, 823, 704 cm-1; MS (ESI) m/z : 421 [M+Na]+; Melting point: 177-178°C.
(2E,6E)-4-tert-butyl-2,6-bis(naphthalen-1-ylmethylene)-
cyclohexanone 1h. Method A was employed starting from 4-
tert-butylcyclohexanone (10 mmol, 1.54 g) and 1-
naphthaldehyde (20 mmol, 2.7 mL). The product was
obtained as a yellow solid (1.98 g, 46%). 1H NMR (300
MHz, CDCl3) δ 8.43 (m, 2H), 8.10-8.05 (m, 2H), 7.95-7.85 (m, 4H), 7.60-7.45 (m, 8H), 3.06
(dd, J = 15.0, 2.4 Hz, 2H), 2.38 (m, 2H), 1.53 (tt, J = 12.6, 3.3 Hz, 1H), 0.78 (s, 9H); 13C
NMR (75 MHz, CDCl3) δ 190.5 (Cq), 138.3 (Cq), 135.4 (CH), 133.7 (Cq), 133.3 (Cq), 132.2
(Cq), 129.0 (CH), 128.7 (CH), 126.9 (CH), 126.6 (CH), 126.3 (CH), 125.2 (CH), 124.9 (CH),
45.1 (CH), 32.7 (Cq), 29.9 (CH2), 27.2 (CH3); IR: νmax= 2955, 1593, 1231, 1196, 1156, 968,
861, 778 cm-1; MS (ESI) m/z : 453 [M+Na]+; Melting point: 146-148°C.
(2E,6E)-4-tert-butyl-2,6-bis(naphthalen-2-
ylmethylene)cyclohexanone 1i. Method A was
employed with 4-tert-butylcyclohexanone (5 mmol,
770 mg) and 2-naphthaldehyde (10 mmol, 1.56 g).
The product was obtained as a yellow solid (1.79 g,
83%). 1H NMR (500 MHz, CDCl3) δ 7.96 (bs, 4H), 7.90-7.80 (m, 6H), 7.60 (d, J = 8.5 Hz,
2H), 7.55-7.45 (m, 4H), 3.31 (d, J = 15.5 Hz, 2H), 2.58 (t, J ~14 Hz, 2H), 1.55-1.50 (m, 1H),
0.97 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 190.7 (Cq), 137.1 (CH), 136.6 (Cq), 133.8 (2Cq),
133.3 (Cq), 133.2 (Cq), 130.4 (CH), 128.6 (CH), 128.2 (CH), 127.8 (CH), 127.7 (CH), 127.0
(CH), 126.6 (CH), 44.7 (CH), 32.7 (Cq), 29.8 (CH2), 27.4 (CH3): IR: νmax= 2356, 1692, 1595,
1563, 1429, 1297, 992, 747, 724 cm-1; MS (ESI) m/z : 453 [M+Na]+; Melting point: 191-
193°C.
(2E,6E)-4-tert-butyl-2,6-bis(furan-2-ylmethylene)cyclohexanone
1j. Method A was employed starting from 4-tert-
butylcyclohexanone (10 mmol, 1.54 g) and 2-furaldehyde (20
mmol, 1.65 mL). The product (2.45g, 79%) was obtained as a
yellow solid. 1H NMR (300 MHz, CDCl3) δ 7.58 (d, J = 1.8 Hz, 2H), 7.53 (d, J = 2.4 Hz,
OO
O
O
O
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
6
2H), 6.67 (d, J = 3.4 Hz, 2H), 6.53 (dd, J = 3.4, 1.8 Hz, 2H), 3.38 (dd, J = 16.5, 3.0 Hz, 2H),
2.41 (m, 2H), 1.65-1.55 (tt, J = 12.9, 3.6 Hz, 1H), 1.06 (s, 9H); 13C NMR (75 MHz, CDCl3) δ
189.5 (Cq), 152.9 (Cq), 144.7 (CH), 133.3 (Cq), 123.4 (CH), 116.2 (CH), 112.4 (CH), 43.3
(CH), 32.2 (Cq), 29.4 (CH2), 27.5 (CH3); IR: νmax= 2959, 1596, 1477, 1307, 1239, 730 cm-1;
MS (ESI) m/z : 333 [M+Na]+; Melting point: 136-138°C.
3) Phosphine promoted [3+2] cyclisations on enones 1.
Procedure a: Ethyl 2,3 butadienoate (0,40 mmol) was added to a mixture of enones 1 (0.20
mmol) and cyclohexyldiphenyl phosphine (10 mol %, 0.020 mmol, 5.4 mg) in degazed
toluene (0.7 mL) under argon atmosphere. The solution was stirred at 40°C until completion.
The crude mixture was concentrated in vacuo. Diastereomeric ratios were measured by NMR
on the crude mixture, based on integration of the C=CHPh signals at about 7.5 ppm. The final
product was purified by flash chromatography on silica gel (5% EtOAc / heptanes).
Procedure b: Ethyl 2,3 butadienoate (0,30 mmol) was added to a mixture of enones 1 (0.15
mmol) and either FerroPHANE, A, or t-Bu-Binepine, B (10 mol %, 0.015 mmol) in degazed
toluene (0.5 mL) under argon atmosphere. The solution was stirred at 80°C until completion.
The crude mixture was concentrated in vacuo. Diastereomeric ratios were measured by NMR
on the crude mixture, based on integration of the C=CHPh signals at about 7.5 ppm. The final
product was purified by flash chromatography on silica gel (5% EtOAc / heptanes).
(E)-ethyl 7-benzylidene-9-methyl-6-oxo-4-phenylspiro[4.5]dec-1-ene-1-
carboxylate 2a. Procedure a (catalyst CyPPh2): 95% yield, 90/10 dr;
Procedure b (catalyst (S,S)-FerroPHANE): 91% yield, 76% ee, 80/20 dr;
Pale yellow oil; 1H NMR (300 MHz, CDCl3) δ 7.57 (bs, 1H,
C6H5CH=C), 7.35-7.10 (m, 10H), 6.91 (m, 1H, CH2CH=C), 4.15-4.00
(m, 3H, CH2CH3, CH2CHC6H5), 2.88 (ddd, 2JAB = 18.0 Hz, 3J = 10,2, 1.8 Hz, 1H,
CH2CH=C), 2.75-2.65 (m, 2H, CH2CH=C, CH2CHCH3), 2.13 (ddd, 2JAB = 15.3 Hz, 3J = 12.6,
3.0 Hz, 1H, CH2CHCH3), 1.85 (dt, 2JAB = 13.8, 3J ≈ 4J = 3.0 Hz, 1H, CH2CHCH3), 1.60 (t, 2J
≈ 3J = 13 Hz, 1H, CH2CHCH3), 1.18 (t, 3J = 6.9 Hz, 3H, CH2CH3), 0.54 (d, 3J = 6.6 Hz, 3H,
CHCH3), 0.40-0.25 (m, 1H, CHCH3); 13C NMR (75 MHz, CDCl3) δ 205.2 (Cq), 163.8 (Cq),
143.4 (Cq), 143.3 (CH2CH=C), 139.1 (Cq), 136.7 (Cq), 136.1 (Cq), 136.0 (C6H5CH=C),
130.5 (2CH), 128.6 (2CH), 128.5 (CH), 128.4 (2CH), 128.4 (2CH), 127.5 (CH), 62.9 (Cq),
60.7 (CH2CH3), 56.1 (CH2CHC6H5), 37.5 (CH2), 36.6 (CH2), 35.7 (CH2), 26.5 (CHCH3), 22.0
(CHCH3), 14.3 (CH2CH3); IR: νmax= 2924, 1706, 1592, 1491, 1445, 1242, 1075, 1026, 904,
O
Ph
Ph
EtOOC
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
7
750, 696 cm-1; HRMS (ESI) calcd. For C27H28NaO3 [M+Na]+: 423.1936, found: 423.1921;
HPLC Analysis: 76% ee [Daicel CHIRACEL IC, 10% iPrOH/n-heptane, 1mL/min, 300 nm,
retention times: 19.8 min (major) and 34.8 min (minor)]. Minor diastereoisomer: selected 1H
NMR data (300 MHz, CDCl3) δ 7.67 (bs), 6.99 (dd, J = 3.0, 2.0 Hz), 4.21 (dd, J = 11.1, 7.5
Hz), 1.40 (t, J = 13.0 Hz), 0.75 (d, J = 6.6 Hz).
(E)-ethyl 7-benzylidene-9-isopropyl-6-oxo-4-phenylspiro[4.5]dec-1-ene-
1-carboxylate 2b. Procedure a (catalyst CyPPh2): 93% yield, 85/15 dr;
Procedure b (catalyst (S,S)-FerroPHANE): 44% yield, 82% ee, 80/20 dr;
Pale yellow oil; 1H NMR (500 MHz, CDCl3) δ 7.65 (d, J = 2.5 Hz, 1H),
7.40-7.15 (m, 10H), 7.00 (t, J = 2.0 Hz, 1H), 4.25-4.10 (m, 3H), 2.96
(ddd, J = 18.0, 10.0, 2.0 Hz, 1H), 2.80-2.75 (m, 2H), 2.24 (ddd, J = 15.5, 12.2, 3.0 Hz, 1H),
1.93 (dt, J = 13.5, 3.0 Hz, 1H), 1.69 (t, J = 13.0 Hz, 1H), 1.25 (t, J = 7.0 Hz, 3H), 1.20-1.10
(m, 1H), 0.57 (d, J = 6.5 Hz, 3H), 0.54 (d, J = 6.5 Hz, 3H), 0.30-0.20 (m, 1H); 13C NMR (75
MHz, CDCl3) δ 205.4 (Cq), 163.8 (Cq), 143.5 (CH), 143.3 (Cq), 139.1 (Cq), 136.9 (Cq),
136.2 (Cq), 136.1 (CH), 130.4 (2CH), 128.9 (2CH), 128.5 (2CH), 128.4 (3CH), 127.4 (CH),
62.8 (Cq), 60.6 (CH2), 55.9 (CH), 36.6 (CH), 35.8 (CH2), 32.3 (CH), 31.8 (CH2), 31.7 (CH2),
19.6 (CH3), 18.9 (CH3), 14.2 (CH3); IR: νmax= 2956, 2360, 1708, 1592, 1446, 1326, 1244,
1091, 1027, 911, 865 cm-1; HRMS (ESI) calcd. For C29H32NaO3 [M+Na]+: 451.2249, found:
451.2259; HPLC Analysis: 82% ee [Daicel CHIRACEL IA, 10% iPrOH/n-heptane,
1mL/min, 300 nm, retention times: 7.7 min (minor) and 10.2 min (major)]; Minor
diastereoisomer: selected 1H NMR data (500 MHz, CDCl3) δ 7.68 (br), 7.04 (dd, J = 2.9, 1.95
Hz), 0.73 (dd, J = 7.0, 5.5 Hz).
(E)-ethyl 7-benzylidene-9-tert-butyl-6-oxo-4-phenylspiro[4.5]dec-1-ene-
1-carboxylate 2c. Procedure a (catalyst CyPPh2): 92% yield, >95/5 dr;
Procedure b (catalyst (S,S)-FerroPHANE): 98% yield, 92% ee, >95/5 dr;
White solid; 1H NMR (300 MHz, CDCl3) δ 7.56 (d, J = 2.4 Hz, 1H), 7.30-
7.10 (m, 10H), 6.95 (t, J = 2.7 Hz, 1H), 4.15-4.00 (m, 3H), 2.90 (ddd, J =
18.3, 9.6, 2.1 Hz, 1H), 2.83 (dt, J = 14.4, 3.0 Hz, 1H), 2.71 (ddd, J = 18.3, 8.1, 3.0 Hz, 1H),
2.15 (td, J = 15.0, 2.7 Hz, 1H), 1.92 (dt, J = 13.8, 2.7 Hz, 1H), 1.65 (t, J = 13.2 Hz, 1H), 1.18
(t, J = 6.9 Hz, 3H), 0.49 (s, 9H), 0.27 (tt, J = 13.0, 3.5 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ
205.4 (Cq), 163.8 (Cq), 143.6 (CH), 143.3 (Cq), 139.0 (Cq), 137.4 (Cq), 136.2 (Cq), 135.9
(CH), 130.2 (2CH), 129.1 (2CH), 128.5 (2CH), 128.4 (2CH), 128.3 (CH), 127.4 (CH), 63.0
(Cq), 60.6 (CH2), 55.8 (CH), 40.2 (CH), 35.8 (CH2), 32.2 (Cq), 29.9 (CH2), 29.2 (CH2), 27.0
O
Ph
Ph
EtOOC
O
PhPh
COOEt
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
8
(3CH3), 14.2 (CH3); IR: νmax= 2946, 1697, 1667, 1588, 1370, 1327, 1243, 1232, 1162, 1095,
1027, 754, 697 cm-1; HRMS (ESI) calcd. For C30H34NaO3 [M+Na]+: 465.2406, found:
465.2397; HPLC Analysis: 92% ee [Daicel CHIRACEL IC, 10% iPrOH/n-heptane,
1mL/min, 300 nm, retention times: 16.4 min (major) and 40.0 min (minor)]; [α]D24 = + 290 (c
= 0.91, CHCl3); Melting point: 128-130°C.
(E)-ethyl 7-benzylidene-6-oxo-1,9-diphenylspiro[4.5]dec-1-ene-2-
carboxylate 2d. Procedure a (catalyst CyPPh2): 86% yield, 90/10 dr;
Procedure b (catalyst (S,S)-FerroPHANE): 98% yield, 92% ee, 85/15
dr; White solid; 1H NMR (500 MHz, CDCl3) δ 7.79 (bs, 1H), 7.40-7.15
(m, 13H), 7.02 (bs, 1H), 6.80 (d, J = 7.5 Hz, 2H), 4.30-4.20 (m, 3H),
3.05-2.90 (m, 2H), 2.85-2.75 (m, 2H), 2.24 (dd, J = 14.0, 13.0 Hz, 1H), 2.18 (d, J = 13.0 Hz,
1H), 1.65-1.60 (m, 1H), 1.33 (t, J = 7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 204.7 (Cq),
163.8 (Cq), 145.1 (Cq), 143.4 (Cq), 143.1 (CH), 138.9 (Cq), 136.9 (CH), 136.4 (Cq), 135.8
(Cq), 130.5 (2CH), 128.9 (2CH), 128.8 (2CH), 128.6 (2CH), 128.5 (3CH), 127.7 (CH), 126.8
(2CH), 126.5 (CH), 63.3 (Cq), 60.8 (CH2), 56.2 (CH), 37.8 (CH), 37.2 (CH2), 35.5 (CH2),
35.2 (CH2), 14.3 (CH3); IR: νmax= 2932, 1697, 1592, 1371, 1327, 1240, 1151, 760, 747, 693
cm-1; HRMS (ESI) calcd. For C32H30NaO3 [M+Na]+: 485.2093, found: 485.2073; HPLC
Analysis: 92% ee [Daicel CHIRACEL IA, 5% iPrOH/n-heptane, 1ml/min, 270 nm, retention
times: 13.8 min (minor) and 18.4 min (major)]; Melting point: 165-166°C.
(E)-tert-butyl 7-benzylidene-9-methyl-6-oxo-4-phenylspiro[4.5]dec-
1-ene-1-carboxylate 3a. Procedure a (catalyst CyPPh2): 90% yield,
85/15 dr; Procedure b (catalyst (S,S)-FerroPHANE): 86% yield,
90% ee, 80/20 dr; White solid; 1H NMR (300 MHz, CDCl3) δ 7.57
(d, J = 2.4 Hz, 1H), 7.35-7.05 (m, 10H), 6.85 (t, J = 2.4 Hz, 1H),
3.98 (m, 1H), 2.86 (ddd, J = 17.7, 10.2, 2.1 Hz, 1H), 2.70-2.60 (m,
1H), 2.08 (ddd, J = 15.3, 12.6, 3.0 Hz, 1H), 1.83 (dt, J = 13.8, 3.0 Hz, 1H), 1.59 (t, J = 12.6
Hz, 2H), 1.37 (s, 9 H), 0.54 (d, J = 6.6 Hz, 3H), 0.35-0.25 (m, 1H); 13C NMR (75 MHz,
CDCl3) δ 205.1 (Cq), 163.1 (Cq), 144.6 (Cq), 142.8 (CH), 139.3 (Cq), 136.8 (Cq), 136.2 (Cq),
135.9 (CH), 130.4 (2CH), 128.6 (2CH), 128.44 (CH), 128.41 (4CH), 127.43 (CH), 81.2 (Cq),
62.9 (Cq), 56.5 (CH), 37.5 (CH2), 36.7 (CH2), 35.4 (CH2), 28.2 (CH3), 26.3 (CH), 22.0 (CH3);
IR: νmax= 2919, 1693, 1671, 1590, 1445, 1332, 1244, 1148, 1076, 1022, 847 cm-1; Melting
point: 142-144°C; HRMS (ESI) calcd. For C29H32NaO3 [M+Na]+: 451.2249, found:
OCOOtBu
Ph
O
PhPh
COOEt
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
9
451.2256; HPLC Analysis: 90% ee [Daicel CHIRACEL IA, 5% iPrOH/n-heptane,
1mL/min, 300 nm, retention times: 7.4 min (minor) and 12.1 min (major)].
(E)-tert-butyl 7-benzylidene-9-isopropyl-6-oxo-4-phenylspiro[4.5]-
dec-1-ene-1-carboxylate 3b. Procedure a (catalyst CyPPh2): 91%
yield, 70/30 dr; Procedure b (catalyst (S,S)-FerroPHANE): 43%
yield, 86% ee, 70/30 dr; Pale yellow oil; Selected data from the
mixture of two diastereoisomers: 1H NMR (300 MHz, CDCl3) δ
7.67 (d, J = 2.5 Hz, 1H), 7.45-7.15 (m, 10H), 6.98 (m, 1H), 4.09 (dd, J = 9.0, 8.5 Hz, 1H),
3.00-2.90 (m, 1H), 2.80-2.70 (m, 2H), 2.24 (td, J = 15.5, 2.5 Hz, 1H), 1.95 (broad d, J = 13.5
Hz, 1H), 1.73 (t, J = 13.5 Hz, 1H), 1.46 (s, 9H), 1.25-1.15 (m, 1H), 0.62 (d, J = 7.0 Hz, 3H),
0.58 (d, J = 6.5 Hz, 3H), 0.30-0.20 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 205.4 (Cq), 163.1
(Cq), 144.5 (Cq), 142.9 (CH), 137.1 (Cq), 136.3 (Cq), 135.9 (CH), 130.3 (2CH), 129.0
(2CH), 128.4 (4CH), 128.3 (CH), 127.3 (CH), 81.1 (Cq), 62.8 (Cq), 56.4 (CH), 36.3 (CH2),
35.5 (CH), 32.3 (CH2), 31.85 (CH), 31.78 (CH), 28.2 (CH3), 19.6 (CH3), 18.9 (CH3); IR:
νmax= 2927, 1702, 1674, 1591, 1366, 1161, 935, 754, 696 cm-1; HRMS (ESI) calcd. For
C31H36NaO3 [M+Na]+: 479.2562, found: 479.2581; HPLC Analysis: 86% ee [Daicel
CHIRACEL IA, 2% EtOH/n-heptane, 1mL/min, 300 nm, retention times: 11.3 min (minor)
and 15.4 min (major)].
(E)-tert-butyl 7-benzylidene-9-tert-butyl-6-oxo-4-phenylspiro[4.5]-
dec-1-ene-1-carboxylate 3c. Procedure a (catalyst CyPPh2): 87%
yield, 90/10 dr; Procedure b (catalyst (S,S)-FerroPHANE): 71%
yield, 95% ee, 90/10 dr; Pale yellow solid; 1H NMR (500 MHz,
CDCl3) δ 7.65 (d, J = 1.5 Hz, 1H), 7.45-7.15 (m, 10H), 6.99 (br, 1H), 4.06 (t, J = 9.0 Hz, 1H),
2.95 (ddd, J = 18.0, 9.5, 2.0 Hz, 1H), 2.91 (m, 1H), 2.78 (ddd, J = 18.0, 8.0, 3.0 Hz, 1H), 2.21
(m, 1H), 1.99 (m, 1H), 1.75 (t, J = 13.0 Hz, 1H), 1.47 (s, 9H), 0.60 (s, 9H), 0.33 (m, 1H); 13C
NMR (75 MHz, CDCl3) δ 205.4 (Cq), 163.2 (Cq), 144.6 (Cq), 143.0 (CH), 139.3 (Cq), 137.6
(Cq), 136.3 (Cq), 135.8 (CH), 130.2 (2CH), 129.2 (2CH), 128.5 (4CH), 128.4 (CH), 127.4
(CH), 81.2 (Cq), 62.9 (Cq), 56.3 (CH), 39.9 (CH), 35.6 (CH2), 32.3 (Cq), 29.9 (CH2), 29.2
(CH2), 28.3 (CH3), 27.0 (CH3); IR: νmax= 2965, 1701, 1586, 1365, 1253, 1161, 1105, 758, 691
cm-1; Melting point: 123-126°C; HRMS (ESI) calcd. For C32H38NaO3 [M+Na]+: 493.2719,
found: 493.2713; HPLC Analysis: 95% ee [Daicel CHIRACEL IA, 5% iPrOH/n-heptane,
1ml/min, 300 nm, retention times: 6.5 min (minor) and 8.4 min (major)].
OCOOtBu
OCOOtBu
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
10
(E)-tert-butyl 7-benzylidene-6-oxo-4,9-diphenylspiro[4.5]dec-1-ene-1-
carboxylate 3d. Procedure a (catalyst CyPPh2): 64% yield, 85/15 dr;
White solid; 1H NMR (500 MHz, CDCl3) δ 7.79 (m, 1H), 7.40-6.95 (m,
15H), 6.82 (d, J = 7.5 Hz, 1H), 4.23 (dd, J = 10.0, 8.0 Hz, 1H), 3.00-
2.90 (m, 2H), 2.90-2.70 (m, 2H), 2.25 (t, J = 13.5 Hz, 1H), 2.15-2.10
(m, 1H), 1.65-1.55 (m, 1H), 1.53 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 204.6 (Cq), 163.0
(Cq), 145.2 (Cq), 144.4 (Cq), 142.9 (CH), 139.1 (Cq), 136.8 (CH), 136.5 (Cq), 135.9 (Cq),
130.4 (CH), 128.9 (CH), 128.8 (CH), 128.6 (CH), 128.5 (CH), 127.7 (CH), 126.7 (CH), 126.5
(CH), 81.3 (Cq), 63.2 (Cq), 56.6 (CH), 37.6 (CH), 37.1 (CH2), 35.3 (CH2), 35.2 (CH2), 28.3
(CH3); IR: νmax= 3060, 2979, 1695, 1591, 1338, 1243, 1157, 1122, 945, 750, 692 cm-1;
HRMS (ESI) calcd. For C34H34NaO3 [M+Na]+: 513.2406, found: 513.2406; HPLC Analysis:
90% ee [Daicel CHIRACEL IA, 5% EtOH/n-heptane, 1mL/min, 300 nm, retention times: 6.3
min and 7.3 min]; Melting point: 130-131°C.
(E)-ethyl 9-tert-butyl-7-(4-methoxybenzylidene)-4-(4-
methoxyphenyl)-6-oxospiro[4.5]dec-1-ene-1-carboxylate 2e.
Procedure b (catalyst (S,S)-FerroPHANE): 91% yield, 93%
ee, >95/5 dr; Colorless oil; 1H NMR (300 MHz, CDCl3) δ
7.63 (d, J = 2.1 Hz, 1H), 7.38 (d, J = 8.7 Hz, 2H), 7.12 (d, J
= 8.4 Hz, 2H), 6.99 (t, J = 2.4 Hz, 1H), 6.92 (d, J = 6.9 Hz,
2H), 6.78 (d, J = 8.7 Hz, 2H), 4.20-4.05 (m, 3H), 3.83 (s, 3H), 3.75 (s, 3H), 2.95-2.85 (m,
2H), 2.76 (ddd, J = 18.3, 8.1, 3.0 Hz, 1H), 2.30-2.20 (m, 1H), 1.96 (dt, J = 13.5, 3.0 Hz, 1H),
1.70 (t, J = 13.2 Hz, 1H), 1 .24 (t, J = 6.9 Hz, 3H), 0.61 (s, 9H), 0.43 (tt, J = 12.6, 3.0 Hz,
1H); 13C NMR (75 MHz, CDCl3) δ 205.2 (Cq), 163.9 (Cq), 159.9 (Cq), 158.9 (Cq), 143.5
(CH), 143.4 (Cq), 136.1 (CH), 135.2 (Cq), 132.2 (2CH), 131.3 (Cq), 130.1 (2CH), 128.8
(Cq), 114.0 (2CH), 113.9 (2CH), 62.7 (Cq), 60.5 (CH2), 55.5 (CH3), 55.4 (CH3), 55.0 (CH),
40.0 (CH), 36.1 (CH2), 32.2 (Cq), 29.8 (CH2), 29.3 (CH2), 27.2 (3CH3), 14.2 (CH3); IR:
νmax= 2953, 2358, 1709, 1604, 1509, 1366, 1248, 1162, 1030, 830, 730 cm-1; HRMS (ESI)
calcd. For C32H38NaO5 [M+Na]+: 525.2617, found: 555.2601; HPLC Analysis: 94% ee
[Daicel CHIRACEL IA, 5% iPrOH/n-heptane, 1mL/min, 300 nm, retention times: 22.4 min
(minor) and 43.8 min major)]; [α]D24 = +355 (c = 1.23, CHCl3).
OEtOOC
MeO
OMe
Ph
O
PhPh
COOtBu
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
11
(E)-ethyl 9-tert-butyl-7-(4-methylbenzylidene)-6-oxo-4-p-tolyl-
spiro[4.5]dec-1-ene-1-carboxylate 2f. Procedure b (catalyst (S,S)-
FerroPHANE): 77% yield, 90% ee, 95/5 dr; White solid; 1H NMR (300 MHz, CDCl3) δ 7.62 (d, J = 2.1 Hz, 1H), 7.30 (d, J
= 8.1 Hz, 2H), 7.19 (d, J = 8.1 Hz, 2H), 7.09 (d, J = 8.4 Hz, 2H),
7.04 (d, J = 8.4 Hz, 2H), 7.01 (t, J = 2.4 Hz, 1H), 4.30-4.00 (m, 3H), 3.00-2.85 (m, 2H),
2.76(ddd, J = 18.0, 7.8, 3.0 Hz, 1H), 2.37 (s, 3H), 2.29 (s, 3H), 2.25-2.15 (m, 1H), 1.97 (dt, J
= 13.5, 3.0 Hz, 1H), 1.70 (t, J = 13.2 Hz, 1H), 1.24 (t, J = 7.2 Hz, 3H), 0.58 (s, 9H), 0.37 (tt, J
= 12.9, 3.0 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 205.5 (Cq), 163.9 (Cq), 143.5 (CH), 143.4
(Cq), 138.6 (Cq), 137.0 (Cq), 136.5 (Cq), 136.1 (CH), 136.0 (Cq), 133.4 (Cq), 130.4 (2CH),
129.2 (2CH), 129.1 (2CH), 129.0 (2CH), 62.8 (Cq), 60.6 (CH2), 55.5 (CH), 40.0 (CH), 35.9
(CH2), 32.3 (Cq), 29.9 (CH2), 29.3 (CH2), 27.1 (3CH3), 21.5 (CH3), 21.1 (CH3), 14.2 (CH3);
IR: νmax= 2945, 1701, 1670, 1597, 1435, 1367, 1233, 1160, 1093, 1029, 813, 755 cm-1;
Melting point: 172-173°C; HRMS (ESI) calcd. For C32H38NaO3 [M+Na]+: 493.2719, found:
493.2735; HPLC Analysis: 90% ee [Daicel CHIRACEL IA, 5% iPrOH/n-heptane,
1mL/min, 300 nm, retention times: 11.5 min (minor) and 17.9 min major)]; [α]D24 = +320 (c =
0.87, CHCl3).
(E)-ethyl 9-tert-butyl-7-(4-chlorobenzylidene)-4-(4-chloro
phenyl)-6-oxospiro[4.5]dec-1-ene-1-carboxylate 2g. Procedure b
(catalyst (S,S)-FerroPHANE): 86% yield, 86% ee, >95/5 dr;
White solid; 1H NMR (300 MHz, CDCl3) δ 7.57 (d, J = 2.4 Hz,
1H), 7.36 (d, J = 8.7 Hz, 2H), 7.30 (d, J = 8.7 Hz, 2H), 7.23 (d, J
= 8.5 Hz, 2H), 7.14 (d, J = 8.5 Hz, 2H), 7.00 (t, 3J = 2.5 Hz, 1H,
CH2CH=C), 4.20-4.00 (m, 3H), 2.95-2.75 (m, 3H), 2.25 (m, 1H), 1.95 (dt, J = 13.8, 2.7 Hz,
1H), 1.72 (t, J = 13.2 Hz, 1H), 1.25 (t, J = 7.2 Hz, 3H), 0.59 (s, 9H), 0.29 (tt, J = 12.9, 2.7 Hz,
1H); 13C NMR (75 MHz, CDCl3) δ 204.8 (Cq), 163.7 (Cq), 143.3 (CH, Cq), 137.7 (Cq),
137.5 (Cq), 134.9 (CH), 134.5 (Cq), 134.4 (Cq), 133.2 (Cq), 131.5 (2CH), 130.4 (2CH), 128.8
(2CH), 128.6 (2CH), 62.8 (Cq), 60.7 (CH2), 54.9 (CH), 40.5 (CH), 35.9 (CH2), 32.3 (Cq),
29.8 (CH2), 29.2 (CH2), 27.1 (CH3), 14.3 (CH3); IR: νmax= 2942, 1704, 1587, 1491, 1369,
1235, 1163, 1089, 1013, 831, 760 cm-1; Melting point: 145-147°C; HRMS (ESI) calcd. For
C30H32NaCl2O3 [M+Na]+: 533.1626, found: 533.1608; HPLC Analysis: 86% ee [Daicel
CHIRACEL IA, 5% iPrOH/n-heptane, 1mL/min, 300 nm, retention times: 11.6 min (minor)
and 15.8 min major)]; [α]D24 = +280 (c = 1.0, CHCl3).
OEtOOC
OEtOOC
Cl
Cl
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
12
(E)-ethyl 9-tert-butyl-4-(naphthalen-1-yl)-7-(naphthalen-1-
ylmethylene)-6-oxospiro[4.5]dec-1-ene-1-carboxylate 2h
Procedure b (catalyst (S,S)-FerroPHANE): 95% yield, 85%
ee, 95/5 dr; Pale yellow oil; 1H NMR (500 MHz, CDCl3) δ
8.14 (d, J = 8.5 Hz, 1H), 7.95 (br, 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.79 (dd, J = 12.5, 8.5 Hz,
2H), 7.72 (d, J = 8.0 Hz, 1H), 7.66 (d, J = 7.0 Hz, 1H), 7.55-7.20 (m, 7H), 7.13 (t, J = 2.5 Hz,
1H), 6.95 (d, J = 7.0 Hz, 1H), 5.02 (t, J = 9.0 Hz, 1H), 4.30-4.20 (m, 2H), 3.22 (ddd, J = 18.5,
10.0, 2.0 Hz, 1H), 2.96 (ddd, J = 18.0, 7.5, 3.0 Hz, 1H), 2.28 (dt, J = 14.5, 2.8 Hz, 1H), 2.19
(dt, J = 14.0, 2.5 Hz, 1H), 1.97 (m, 1H), 1.75 (t, J = 13.0 Hz, 1H), 1.33 (t, J = 7.0 Hz, 3H),
0.37 (s, 9H), -0.1 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 206.4 (Cq), 163.9 (Cq), 143.5 (Cq),
143.2 (CH), 139.4 (Cq), 135.4 (Cq), 134.9 (CH), 134.1 (Cq), 133.6 (Cq), 133.4 (Cq), 132.7
(Cq), 131.6 (Cq), 128.9 (CH), 128.3 (CH), 128.2 (CH), 126.7 (CH), 126.3 (CH), 126.2 (CH),
126.1 (CH), 126.0 (CH), 125.9 (CH), 125.4 (CH), 125.3 (CH), 125.0 (CH), 124.5 (CH), 63.5
(Cq), 60.7 (CH2), 50.0 (CH), 40.9 (CH), 37.8 (CH2), 32.2 (Cq), 31.0 (CH2), 29.1 (CH2), 26.9
(CH3), 14.4 (CH3); IR: νmax= 2954, 1704, 1597, 1440, 1366, 1246, 1160, 1046, 907, 777, 728
cm-1; HRMS (ESI) calcd. For C38H38KO3 [M+K]+: 581.2458, found: 581.2482; HPLC
Analysis: 81% ee [Daicel CHIRACEL IA, 5% iPrOH/n-heptane, 1mL/min, 300 nm,
retention times: 10.9 min (minor) and 18.4 min major)]; [α]D24 = -20 (c = 1.2, CHCl3).
(E)-ethyl 9-tert-butyl-4-(naphthalen-2-yl)-7-(naphthalen-2-
ylmethylene)-6-oxospiro[4.5]dec-1-ene-1-carboxylate 2i.
Procedure b (catalyst (S,S)-FerroPHANE): 72% yield, 90%
ee, 95/5 dr; White solid; 1H NMR (300 MHz, CDCl3) δ
7.90-7.70 (m, 9H), 7.55-7.40 (m, 5H), 7.31 (dd, J = 8.1, 1.5
Hz, 1H), 7.10 (t, J = 2.7 Hz, 1H), 4.35-4.15 (m, 3H), 3.14
(ddd, J = 18.0, 9.6, 2.1 Hz, 1H), 2.98 (m, 1H), 2.90 (ddd, J =18.3, 7.8, 3.0 Hz, 1H), 2.40-2.30
(m, 1H), 2.11 (dt, J = 13.8, 2.7 Hz, 1H), 1.80 (t, J = 12.9 Hz, 1H), 1.30 (t, J = 7.2 Hz, 3H),
0.41 (s, 9H), 0.31 (dt, J = 12.9, 3.0 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 205.4 (Cq), 163.9
(Cq), 143.6 (CH), 143.4 (Cq), 137.7 (Cq), 136.6 (Cq), 136.2 (CH), 133.7 (Cq), 133.4 (Cq),
133.2 (Cq), 133.1 (Cq), 132.8 (Cq), 130.1 (CH), 128.4 (CH), 128.0 (3CH), 127.79 (CH),
127.75 (CH), 127.62 (CH), 127.59 (CH), 127.3 (CH), 126.8 (CH), 126.5 (CH), 126.3 (CH),
125.9 (CH), 63.2 (Cq), 60.7 (CH2), 56.0 (CH), 40.3 (CH), 36.0 (CH2), 32.1 (Cq), 30.1 (CH2),
29.4 (CH2), 26.9 (CH3), 14.3 (CH3); IR: νmax= 2956, 2359, 1706, 1585, 1366, 1241, 1162,
1097, 855, 818, 746, 668 cm-1; Melting point: 165-166°C; HRMS (ESI) calcd. For
C38H38NaO3 [M+Na]+: 565.2719, found: 565.2736; HPLC Analysis: 90% ee [Daicel
OEtOOC
OEtOOC
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
13
CHIRACEL IA, 5% iPrOH/n-heptane, 1mL/min, 300 nm, retention times: 14.8 min (minor)
and 27.8 min (major)]; [α]D24 = +343 (c = 0.88, CHCl3).
(E)-ethyl 9-tert-butyl-4-(furan-2-yl)-7-(furan-2-ylmethylene)-6-
oxospiro[4.5]dec-1-ene-1-carboxylate 2j. Procedure b (catalyst
(S,S)-FerroPHANE): 57% yield, 92% ee, 75/25 dr; Yellow oil; 1H
NMR (300 MHz, CDCl3) δ 7.54 (d, J = 1.5 Hz, 1H), 7.49 (d, J = 2.4
Hz, 1H), 7.29 (dd, J = 1.5, 0.6 Hz, 1H), 6.91 (t, J = 2.4 Hz, 1H), 6.62
(d, J = 3.3 Hz, 1H), 6.49 (dd, J = 3.3, 1.8 Hz, 1H), 6.28 (dd, J = 3.0, 1.8 Hz, 1H), 6.11 (d, J =
3.0 Hz, 1H), 4.20-4.00 (m, 3H), 3.18 (dt, J = 16.5, 3.0 Hz, 1H), 2.88 (ddd, J = 18.0, 10.5, 3.0
Hz, 1H), 2.77 (ddd, J = 18.0, 8.1, 3.0 Hz, 1H), 2.31 (ddd, J = 15.9, 13.2, 2.7 Hz, 1H), 2.03 (dt,
J = 13.8, 2.7 Hz, 1H), 1.65 (t, J = 13.2 Hz, 1H), 1.19 (t, J = 7.2 Hz, 3H), 0.76 (s, 9H), 0.44 (tt,
J = 12.9, 3.6 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 203.6 (Cq), 163.5 (Cq), 153.5 (Cq),
152.9 (Cq), 144.6 (CH), 143.8 (Cq), 142.6 (CH), 141.4 (CH), 133.1 (Cq), 123.5 (CH), 116.2
(CH), 112.4 (CH), 110.6 (CH), 108.1 (CH), 62.2 (Cq), 60.6 (CH2), 49.0 (CH), 39.4 (CH),
34.7 (CH2), 32.3 (Cq), 30.0 (CH2), 29.4 (CH2), 27.2 (CH3), 14.1 (CH3); IR: νmax= 2960,
1709, 1670, 1591, 1243, 1103, 735 cm-1; HRMS (ESI) calcd. For C26H30NaO5 [M+Na]+:
423.2171, found: 423.2176; HPLC Analysis: 92% ee [Daicel CHIRACEL IA, 5% iPrOH/n-
heptane, 1mL/min, 330 nm, retention times: 22.3 min (minor) and 35.8 min (major)]; [α]D24 =
+166 (c = 0.62, CHCl3).
(E)-ethyl 4-benzylidene-3-oxo-5'-phenylspiro[bicyclo[3.1.0]hexane-2,1'-
cyclopent[2]ene]-2'-carboxylate 5a. Procedure b (catalyst (S,S)-
FerroPHANE): 63% yield, 83% ee, 95/5 dr; Orange oil; 1H NMR (500
MHz, CDCl3) δ 7.91 (m, 2H), 7.65-7.45 (m, 9H), 7.38 (t, J = 2.7 Hz, 1H),
4.33 (m, 2H), 4.08 (dd, J = 8.4, 6.0 Hz, 1H), 3.46 (ddd, J = 18.6, 8.4, 2.7 Hz, 1H), 3.06 (ddd,
J = 18.9, 6.3, 2.7 Hz, 1H), 2.75-2.60 (m, 1H), 1.85-1.75 (m, 1H), 1.39 (t, J = 6.9 Hz, 3H),
1.17-1.10 (m, 1H), 0.03 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 209.1 (Cq), 163.9 (Cq), 146.2
(CH), 142.6 (Cq), 140.4 (Cq), 139.3 (Cq), 135.9 (Cq), 131.1 (CH), 130.1 (2CH), 129.1 (CH),
128.8 (2CH), 128.7 (2CH), 128.4 (2CH), 126.9 (CH), 67.0 (Cq), 60.6 (CH2), 52.5 (CH), 40.0
(CH2), 22.3 (CH), 20.2 (CH), 15.9 (CH2), 14.1 (CH3); IR: νmax= 2928, 1708, 1625, 1493,
1325, 1263, 1177, 1112, 1028, 755, 692 cm-1; HRMS (ESI) calcd. For C26H24NaO3
[M+Na]+: 407.1623, found: 407.1634; HPLC Analysis: 86% ee [Daicel CHIRACEL IA,
10% iPrOH/ n-heptane, 1mL/min, 300 nm, retention times: 6.8 min (major) and 7.8 min
(minor)]; [α]D24 = +11 (c = 1.6, CHCl3).
OEtOOC
O
O
O
Ph
Ph
COOEt
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
14
(E)-ethyl 4-benzylidene-6-methyl-3-oxo-5'-phenylspiro[bicyclo[3.1.0]
hexane-2,1'-cyclopent[2]ene]-2'-carboxylate 5b. Procedure b (catalyst
(S,S)-FerroPHANE): 66% yield, 83% ee, 95/5 dr; Orange oil; 1H NMR
(500 MHz, CDCl3) δ 7.63 (d, J = 7.5 Hz, 2H), 7.40-7.20 (m, 9H), 7.11 (t,
J = 2.5 Hz, 1H), 4.08 (m, 2H), 3.77 (dd, J = 9.0, 5.5 Hz, 1H), 3.24 (ddd, J = 19.0, 9.0, 2.5 Hz,
1H), 2.79 (ddd, J = 19.0, 5.5, 2.5 Hz, 1H), 2.23 (m, 1H), 1.25 (m, 1H), 1.14 (t, J = 7.0 Hz,
3H), 0.69 (d, J = 6.0 Hz, 3H), 0.13 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 209.8 (Cq), 163.9
(Cq), 146.0 (CH), 143.5 (Cq), 140.3 (Cq), 138.9 (Cq), 135.9 (Cq), 130.7 (CH), 130.1 (2CH),
129.1 (CH), 128.7 (4CH), 128.4 (2CH), 126.9 (CH), 67.9 (Cq), 60.6 (CH2), 52.4 (CH), 40.5
(CH2), 30.9 (CH), 29.0 (CH), 25.1 (CH) 16 9 (CH3), 14.1 (CH3); IR: νmax= 2924, 1711, 1627,
1448, 1264, 1176, 1102, 1027, 732 cm-1; HRMS (ESI) calcd. For C27H26NaO3 [M+Na]+:
421.1780, found: 421.1786; HPLC Analysis: 83% ee [Daicel CHIRACEL IA, 10% iPrOH/
n-heptane, 1mL/min, 270 nm, retention times: 7.9 min (major) and 10.9 min (minor)]; [α]D24
= +16 (c = 1.5, CHCl3).
O
Ph
Ph
COOEt
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
15
4) NMR spectra and HPLC analysis
(E)-ethyl 7-benzylidene-9-methyl-6-oxo-4-phenylspiro[4.5]dec-1-ene-1-carboxylate 2a 1H NMR (300 MHz, CDCl3):
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5 ppm
0.634
0.647
0.845
0.858
1.256
1.264
1.270
1.278
1.293
1.669
1.696
1.721
1.924
1.930
1.936
1.958
1.963
2.222
2.227
2.232
2.258
2.735
2.741
2.771
2.777
2.782
2.792
2.798
2.813
2.819
2.828
2.834
2.952
2.956
2.972
2.976
4.143
4.159
4.163
4.173
4.178
4.187
4.192
4.201
4.206
7.006
7.011
7.016
7.231
7.237
7.241
7.251
7.255
7.265
7.270
7.282
7.314
7.327
7.333
7.340
7.344
7.378
7.381
7.394
7.404
7.407
7.419
7.671
7.676
0.84
2.74
3.12
1.10
1.00
0.92
2.16
1.02
2.62
0.62
8.80
0.57
13C NMR (75 MHz, CDCl3):
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm
14.255
21.969
26.497
35.725
36.575
37.467
56.086
60.664
62.942
76.750
77.173
77.596
127.492
128.419
128.460
128.500
128.601
130.489
136.071
136.136
136.673
139.094
143.318
143.348
163.837
205.219
OCOOEt
OCOOEt
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
16
HPLC Analysis: Table 2, entry 1: 76% ee [Daicel CHIRACEL IC, 10% iPrOH/n-heptane, 1 mL/min, 300 nm]:
OCOOEt
OCOOEt
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
17
(E)-ethyl 7-benzylidene-9-isopropyl-6-oxo-4-phenylspiro[4.5]dec-1-ene-1-carboxylate 2b 1H NMR (300 MHz, CDCl3):
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm
0.242
0.246
0.537
0.551
0.564
0.577
1.159
1.171
1.231
1.245
1.259
1.661
1.688
1.714
1.913
1.919
1.925
1.946
2.246
2.760
2.766
2.776
2.782
2.790
2.796
2.802
2.812
2.818
2.929
2.933
2.949
2.953
4.099
4.115
4.120
4.127
4.135
4.141
4.149
4.155
4.163
4.170
4.177
4.184
4.191
4.199
6.995
7.000
7.004
7.167
7.196
7.202
7.211
7.222
7.233
7.250
7.275
7.286
7.292
7.298
7.304
7.310
7.315
7.353
7.369
7.376
7.380
7.644
7.649
1.00
5.96
1.17
3.74
1.26
1.01
1.00
2.36
1.18
3.62
1.01
14.11
1.13
13C NMR (75 MHz, CDCl3):
OCOOEt
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
18
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm
14.238
18.929
19.639
31.747
31.822
32.290
35.812
36.641
55.859
60.598
62.817
76.732
77.155
77.579
127.372
128.424
128.464
128.931
130.396
136.095
136.155
136.979
139.074
143.286
143.469
163.813
205.428
HPLC Analysis: Table 2, entry 2: 82% ee [Daicel CHIRACEL IA, 10% iPrOH/n-heptane, 1 mL/min, 300 nm]:
OCOOEt
OCOOEt
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
19
OCOOEt
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
20
(E)-ethyl 7-benzylidene-9-tert-butyl-6-oxo-4-phenylspiro[4.5]dec-1-ene-1-carboxylate 2c
1H NMR (300 MHz, CDCl3):
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm
0.270
0.493
0.537
0.641
1.156
1.180
1.194
1.203
1.649
1.693
1.895
2.807
2.848
2.855
4.005
4.038
4.063
4.086
4.101
4.125
6.938
6.945
6.954
7.123
7.149
7.155
7.170
7.181
7.224
7.240
7.252
7.295
7.309
7.563
7.571
1.21
8.48
4.80
1.36
1.05
1.03
1.17
2.00
3.61
1.19
11.07
1.07
13C NMR (75 MHz, CDCl3):
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm
14.248
27.028
29.166
29.937
32.223
35.799
40.214
55.782
60.580
62.950
76.740
77.163
77.587
127.362
128.358
128.433
128.459
129.131
130.214
135.926
136.177
137.407
139.043
143.268
143.558
163.810
205.437
OCOOEt
OCOOEt
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
21
HPLC Analysis: Table 2, entry 3: 92% ee [Daicel CHIRACEL IC, 10% iPrOH/n-heptane, 1 mL/min, 300 nm]:
OCOOEt
OCOOEt
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
22
(E)-ethyl 7-benzylidene-6-oxo-1,9-diphenylspiro[4.5]dec-1-ene-2-carboxylate 2d 1H NMR (300 MHz, CDCl3):
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0 ppm
1.321
1.335
1.346
1.360
1.564
1.570
1.590
1.596
1.609
1.616
2.122
2.128
2.150
2.200
2.226
2.253
2.787
2.793
2.802
2.808
2.823
2.828
2.838
2.845
2.852
2.878
2.883
2.957
2.974
2.977
2.989
3.010
3.013
4.182
4.197
4.204
4.211
4.218
4.223
4.232
4.237
4.247
4.252
4.259
4.266
4.274
4.280
4.296
6.782
6.796
7.016
7.030
7.143
7.158
7.172
7.198
7.213
7.282
7.340
7.354
7.365
7.368
7.397
7.412
7.780
7.784
3.80
1.22
1.24
1.16
2.34
2.36
3.25
1.86
1.00
13.43
0.74
13C NMR (75 MHz, CDCl3):
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm
14.312
35.180
35.474
37.171
37.847
56.175
60.753
63.295
76.738
77.161
77.584
126.527
126.755
127.692
128.461
128.643
128.797
128.909
130.494
135.823
136.440
136.940
138.929
143.148
143.448
145.080
163.788
204.692
OCOOEt
OCOOEt
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
23
HPLC Analysis: Table 2, entry 4: 92% ee [Daicel CHIRACEL IA, 5% iPrOH/n-heptane, 1 mL/min, 300 nm]:
OCOOEt
OCOOEt
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
24
(E)-tert-butyl 7-benzylidene-9-methyl-6-oxo-4-phenylspiro[4.5]dec-1-ene-1-carboxylate 3a
1H NMR (300 MHz, CDCl3):
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0 ppm
0.379
0.385
0.391
0.398
0.404
0.637
0.650
0.851
0.864
0.893
0.908
0.921
1.283
1.290
1.310
1.464
1.470
1.490
1.498
1.517
1.667
1.693
1.719
1.913
1.918
1.941
1.946
2.154
2.160
2.185
2.210
2.215
2.733
2.739
2.749
2.755
2.761
2.769
2.785
2.791
2.916
2.919
2.937
2.940
2.952
2.955
2.972
4.088
4.104
4.107
4.123
6.950
6.954
7.173
7.188
7.210
7.215
7.245
7.248
7.282
7.306
7.320
7.391
7.400
7.414
7.425
7.670
7.674
7.693
1.03
3.07
0.81
0.74
11.96
1.32
0.24
1.09
1.24
2.24
1.05
1.00
0.19
0.84
0.17
13.24
1.01
0.20
13C NMR (75 MHz, CDCl3):
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm
14.243
14.327
21.160
22.003
22.818
26.314
28.238
35.429
36.706
37.508
56.548
60.505
62.890
76.741
77.164
77.588
81.197
127.429
128.416
128.443
128.597
130.416
135.891
136.161
136.789
139.267
142.792
144.566
163.080
171.244
205.114
OCOOtBu
OCOOtBu
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
25
HPLC Analysis: Table 2, entry 5: 90% ee [Daicel CHIRACEL IA, 5% iPrOH/n-heptane, 1 mL/min, 300 nm]:
OCOOtBu
OCOOtBu
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
26
(E)-tert-butyl 7-benzylidene-9-isopropyl-6-oxo-4-phenylspiro[4.5]dec-1-ene-1-carboxylate 3b 1H NMR (300 MHz, CDCl3):
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0 ppm
0.582
0.596
0.609
0.623
0.759
0.774
0.788
1.194
1.207
1.268
1.280
1.460
1.465
1.500
1.512
1.621
1.679
1.696
1.723
1.750
1.785
1.809
1.939
1.967
2.235
2.751
2.757
2.767
2.773
2.782
2.787
2.792
2.805
2.809
2.924
2.928
2.944
2.948
2.960
4.072
4.090
4.107
6.976
6.980
6.990
7.176
7.192
7.227
7.237
7.246
7.257
7.270
7.272
7.281
7.296
7.322
7.325
7.333
7.337
7.341
7.349
7.395
7.402
7.405
7.417
7.419
7.673
7.678
7.688
1.07
7.22
3.38
1.44
15.64
2.84
1.24
1.17
3.54
1.73
1.00
0.46
1.30
15.33
1.20
13C NMR (75 MHz, CDCl3):
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm
18.929
19.550
19.591
19.643
28.231
28.259
31.662
31.775
31.854
32.040
32.334
32.488
33.025
34.483
35.556
36.373
36.687
56.351
57.101
61.718
62.773
76.741
77.164
77.588
81.131
81.165
127.218
127.340
128.164
128.353
128.403
128.445
128.545
128.962
128.983
130.337
130.635
135.958
136.201
136.290
136.481
137.087
139.248
142.929
143.078
144.551
146.372
163.111
163.841
203.959
205.391
OCOOtBu
OCOOtBu
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
27
HPLC Analysis: Table 2, entry 6: 86% ee [Daicel CHIRACEL IA, 2% EtOH/n-heptane, 1 mL/min, 300 nm]:
OCOOtBu
OCOOtBu
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
28
(E)-tert-butyl 7-benzylidene-9-tert-butyl-6-oxo-4-phenylspiro[4.5]dec-1-ene-1-carboxylate 3c 1H NMR (300 MHz, CDCl3):
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0 ppm
0.094
0.307
0.333
0.358
0.422
0.467
0.604
0.641
0.753
0.890
0.905
0.918
0.964
1.262
1.267
1.287
1.307
1.324
1.338
1.467
1.512
1.619
1.726
1.753
1.779
1.986
2.013
2.176
2.181
2.206
2.232
2.237
2.753
2.759
2.769
2.775
2.789
2.795
2.805
2.811
2.896
2.926
2.945
2.949
2.962
2.981
2.985
4.045
4.062
4.080
6.988
7.193
7.226
7.239
7.245
7.251
7.261
7.282
7.291
7.329
7.343
7.369
7.383
7.390
7.405
7.415
7.420
7.651
7.654
0.97
8.89
10.44
1.24
1.01
1.00
1.28
2.11
0.84
0.81
9.93
0.73
13C NMR (75 MHz, CDCl3):
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm
27.023
28.267
29.216
29.967
32.310
35.624
39.923
56.302
57.201
62.967
76.743
77.166
77.590
81.189
127.276
127.366
128.352
128.479
129.051
129.209
130.182
130.633
135.801
136.267
137.571
139.261
143.027
144.552
163.163
205.436
OCOOtBu
OCOOtBu
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
29
HPLC Analysis: Table 2, entry 7: 95% ee [Daicel CHIRACEL IA, 5% iPrOH /n-heptane, 1 mL/min, 300 nm]:
OCOOtBu
OCOOtBu
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
30
(E)-ethyl 9-tert-butyl-7-(4-methoxybenzylidene)-4-(4-methoxyphenyl)-6-oxospiro[4.5]dec-1-ene-1-carboxylate 2e 1H NMR (300 MHz, CDCl3):
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm
0.429
0.435
0.605
0.643
0.748
1.222
1.236
1.251
1.598
1.681
1.708
1.734
1.948
1.975
2.257
2.282
2.759
2.773
2.779
2.789
2.795
2.864
2.868
2.888
2.900
2.904
2.920
3.753
3.776
3.819
3.830
4.069
4.087
4.097
4.104
4.111
4.119
4.133
4.147
4.150
4.165
4.179
4.187
4.194
4.201
6.772
6.790
6.907
6.924
6.993
6.998
7.002
7.108
7.125
7.257
7.371
7.388
7.622
7.625
1.12
9.43
4.41
1.25
0.99
1.03
1.20
2.12
3.05
3.28
3.32
2.11
2.16
1.05
2.06
2.15
1.00
13C NMR (75 MHz, CDCl3):
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm
14.256
27.173
29.359
29.778
32.257
36.113
40.065
54.987
55.431
55.513
60.536
62.722
76.744
77.167
77.591
113.885
113.999
128.828
130.072
131.343
132.240
135.241
136.100
143.463
143.565
158.968
159.880
163.898
205.222
OEtOOC
MeO
OMe
OEtOOC
MeO
OMe
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
31
HPLC Analysis: Table 3, entry 1: 94% ee [Daicel CHIRACEL IA, 5% iPrOH /n-heptane, 1 mL/min, 300 nm]:
OEtOOC
MeO
OMe
OEtOOC
MeO
OMe
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
32
(E)-ethyl 9-tert-butyl-7-(4-methylbenzylidene)-6-oxo-4-p-tolylspiro[4.5]dec-1-ene-1-carboxylate 2f 1H NMR (300 MHz, CDCl3):
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0 ppm
1.261
1.270
1.284
1.304
1.310
1.702
1.728
1.754
1.979
2.006
2.224
2.229
2.254
2.280
2.285
2.311
2.337
2.372
2.392
2.762
2.768
2.778
2.784
2.799
2.804
2.814
2.820
2.918
2.924
2.947
2.961
2.980
2.984
4.079
4.096
4.114
4.130
4.137
4.144
4.151
4.180
4.199
4.207
4.214
4.221
4.228
4.235
7.031
7.059
7.075
7.105
7.121
7.208
7.224
7.282
7.316
7.332
7.645
0.84
7.28
3.31
1.06
0.83
0.96
2.69
2.76
1.00
1.69
2.76
0.85
3.59
1.69
1.68
0.85
13C NMR (75 MHz, CDCl3):
OEtOOC
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
33
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm
14.259
21.087
21.499
27.107
29.305
29.895
32.253
35.914
40.015
55.467
60.559
62.847
76.740
77.163
77.587
129.013
129.063
129.207
130.448
130.754
133.385
136.022
136.137
136.530
136.965
138.565
143.362
143.643
163.894
205.470
HPLC Analysis: Table 3, entry 2: 90% ee [Daicel CHIRACEL IA, 5% iPrOH /n-heptane, 1 mL/min, 300 nm]:
OEtOOC
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
34
OEtOOC
OEtOOC
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
35
(E)-ethyl 9-tert-butyl-7-(4-chlorobenzylidene)-4-(4-chlorophenyl)-6-oxospiro[4.5]dec-1-ene-1-carboxylate 2g 1H NMR (300 MHz, CDCl3):
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm
0.251
0.284
0.294
0.303
0.327
0.337
0.525
1.158
1.181
1.205
1.612
1.657
1.701
1.850
1.860
1.869
1.896
1.906
1.915
2.126
2.136
2.177
2.185
2.219
2.229
2.666
2.675
2.692
2.702
2.726
2.736
2.752
2.762
2.784
2.791
2.815
2.822
3.981
4.011
4.028
4.040
4.052
4.064
4.070
4.088
4.094
4.107
4.111
4.118
4.131
4.142
4.154
6.916
6.924
6.932
7.052
7.080
7.141
7.149
7.171
7.177
7.190
7.220
7.249
7.276
7.298
7.305
7.504
7.512
1.19
8.45
4.68
1.13
0.96
0.97
3.05
3.41
0.95
8.57
1.00
13C NMR (75 MHz, CDCl3):
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm
14.276
27.084
29.221
29.792
32.316
35.983
40.502
54.949
60.717
62.791
76.738
77.161
77.585
128.594
128.789
130.404
131.540
133.205
134.446
134.497
134.947
137.513
137.656
143.321
163.690
204.767
OEtOOC
Cl
Cl
OEtOOC
Cl
Cl
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
36
HPLC Analysis: Table 3, entry 3: 86% ee [Daicel CHIRACEL IA, 5% iPrOH /n-heptane, 1 mL/min, 300 nm]:
OEtOOC
Cl
Cl
OEtOOC
Cl
Cl
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
37
(E)-ethyl 9-tert-butyl-4-(naphthalen-1-yl)-7-(naphthalen-1-ylmethylene)-6-oxospiro[4.5]dec-1-ene-1-carboxylate 2h 1H NMR (300 MHz, CDCl3):
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm
-0.091
0.311
0.370
0.520
1.311
1.325
1.339
1.720
1.747
1.773
1.966
2.184
2.212
2.276
2.305
2.963
4.206
4.221
4.228
4.242
4.263
4.277
4.284
5.008
5.024
5.043
6.947
6.961
7.127
7.132
7.137
7.247
7.260
7.296
7.299
7.310
7.312
7.319
7.327
7.329
7.335
7.349
7.410
7.424
7.440
7.454
7.456
7.462
7.478
7.487
7.489
7.493
7.504
7.506
7.520
7.653
7.667
7.709
7.725
7.775
7.791
7.799
7.816
7.841
7.857
7.954
7.957
8.135
8.152
1.00
8.98
3.53
1.16
0.98
2.12
1.09
1.03
2.23
1.01
0.94
1.02
7.95
5.42
1.02
1.06
13C NMR (75 MHz, CDCl3):
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm
14.336
26.931
29.077
30.946
32.184
37.771
40.896
49.955
60.705
63.469
76.728
77.152
77.575
124.496
125.060
125.250
125.375
125.884
125.971
126.125
126.195
126.274
126.409
126.722
128.009
128.228
128.312
128.861
131.592
132.655
133.378
133.592
134.079
134.905
135.409
139.374
143.223
143.497
163.914
206.335
OEtOOC
OEtOOC
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
38
HPLC Analysis: Table 3, entry 4: 85% ee [Daicel CHIRACEL IA, 5% iPrOH /n-heptane, 1 mL/min, 300 nm]:
OEtOOC
OEtOOC
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
39
(E)-ethyl 9-tert-butyl-4-(naphthalen-2-yl)-7-(naphthalen-2-ylmethylene)-6-oxospiro[4.5]dec-1-ene-1-carboxylate 2i 1H NMR (300 MHz, CDCl3):
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0 ppm
0.312
0.338
0.364
0.423
0.490
0.701
1.298
1.312
1.326
1.781
1.807
1.834
2.102
2.129
2.337
2.901
2.906
2.916
2.922
2.937
2.942
2.952
2.958
2.977
3.006
3.125
3.144
3.158
3.161
4.180
4.194
4.201
4.216
4.231
4.246
4.260
4.268
4.282
4.314
4.332
4.348
7.115
7.281
7.320
7.337
7.444
7.452
7.460
7.462
7.493
7.505
7.513
7.520
7.523
7.527
7.530
7.723
7.745
7.761
7.769
7.781
7.788
7.799
7.811
7.818
7.830
7.841
7.857
7.880
1.46
9.02
3.30
1.11
1.04
0.96
2.08
1.00
2.84
0.77
1.22
4.37
8.13
13C NMR (75 MHz, CDCl3):
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm
14.246
14.304
22.818
26.889
29.359
29.486
29.785
29.827
30.105
32.053
32.134
35.976
40.343
56.001
60.665
63.165
76.738
77.161
77.584
125.878
126.343
126.467
126.801
127.319
127.589
127.620
127.754
127.799
127.965
128.432
130.089
132.777
133.051
133.239
133.382
133.708
136.161
136.618
137.663
143.439
143.589
163.881
205.384
OEtOOC
OEtOOC
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
40
HPLC Analysis: Table 3, entry 5: 90% ee [Daicel CHIRACEL IA, 5% iPrOH /n-heptane, 1 mL/min, 300 nm]:
OEtOOC
OEtOOC
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
41
(E)-ethyl 9-tert-butyl-4-(furan-2-yl)-7-(furan-2-ylmethylene)-6-oxospiro[4.5]dec-1-ene-1-carboxylate 2j 1H NMR (300 MHz, CDCl3):
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0 ppm
0.432
0.442
0.453
0.761
1.167
1.190
1.214
1.602
1.647
1.691
2.000
2.009
2.019
2.045
2.055
2.254
2.264
2.298
2.308
2.317
2.779
2.789
2.806
2.816
2.829
2.836
2.864
2.871
3.147
3.156
3.211
4.050
4.062
4.074
4.086
4.098
4.110
4.112
4.127
4.136
4.149
4.160
4.172
6.104
6.114
6.274
6.280
6.284
6.290
6.486
6.492
6.497
6.503
6.619
6.630
6.906
6.914
6.922
7.262
7.272
7.281
7.284
7.287
7.289
7.486
7.494
7.538
7.543
7.552
1.13
8.12
3.93
0.94
0.94
1.01
1.24
1.07
1.00
3.13
0.87
1.11
0.99
0.94
0.86
0.96
1.94
13C NMR (75 MHz, CDCl3):
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm
14.161
27.199
29.352
30.028
32.254
34.699
39.385
48.961
60.621
62.158
76.742
77.165
77.589
108.069
110.574
112.356
116.211
123.467
133.146
141.387
142.579
143.792
144.563
152.909
153.464
163.521
203.580
OEtOOC
O
O
OEtOOC
O
O
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
42
HPLC Analysis: Table 3, entry 6: 92% ee [Daicel CHIRACEL IA, 5% iPrOH /n-heptane, 1 mL/min, 330 nm]:
OEtOOC
O
O
OEtOOC
O
O
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
43
(E)-ethyl 4-benzylidene-3-oxo-5'-phenylspiro[bicyclo[3.1.0]hexane-2,1'-cyclopent[2]ene]-2'-carboxylate 5a 1H NMR (300 MHz, CDCl3):
8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm
0.000
0.017
1.096
1.115
1.123
1.142
1.149
1.169
1.363
1.387
1.410
1.502
1.508
1.525
1.762
1.778
1.785
1.789
1.801
1.805
1.812
2.724
2.737
3.027
3.039
3.081
3.089
3.101
3.110
3.410
3.419
3.439
3.448
3.501
3.510
4.054
4.075
4.083
4.103
4.299
4.307
4.323
4.331
4.347
4.355
4.370
4.378
7.369
7.378
7.387
7.463
7.470
7.476
7.486
7.498
7.507
7.516
7.528
7.542
7.556
7.575
7.580
7.590
7.615
7.637
7.644
7.897
7.920
7.925
1.00
1.19
3.03
1.07
1.00
1.03
1.01
1.02
2.02
1.01
9.39
2.09
13C NMR (75 MHz, CDCl3):
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm
14.114
15.916
20.215
22.270
40.023
52.533
60.611
66.968
76.739
77.162
77.585
126.909
128.366
128.676
128.787
129.091
130.147
131.112
135.864
139.341
140.406
142.634
146.157
163.855
209.115
O
Ph
Ph
COOEt
O
Ph
Ph
COOEt
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
44
HPLC Analysis: product 5a: 86% ee [Daicel CHIRACEL IA, 10% iPrOH /n-heptane, 1 mL/min, 300 nm]:
O
Ph
Ph
COOEt
O
Ph
Ph
COOEt
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010
45
(E)-ethyl 4-benzylidene-6-methyl-3-oxo-5'-phenylspiro[bicyclo[3.1.0]hexane-2,1'-cyclopent[2]ene]-2'-carboxylate 5b 1H NMR (300 MHz, CDCl3):
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0 ppm
0.106
0.113
0.117
0.120
0.125
0.133
0.685
0.697
1.122
1.136
1.150
1.237
1.246
1.251
1.259
2.223
2.230
2.237
2.242
2.767
2.772
2.778
2.783
2.805
2.810
2.816
2.821
3.211
3.216
3.229
3.234
3.249
3.254
3.267
3.272
3.755
3.766
3.773
3.784
4.051
4.059
4.068
4.073
4.082
4.087
4.096
4.101
4.111
4.118
7.102
7.107
7.112
7.203
7.206
7.217
7.232
7.253
7.259
7.267
7.275
7.289
7.305
7.310
7.325
7.350
7.366
7.380
7.621
7.636
1.00
3.05
3.18
1.59
1.02
1.06
1.03
1.00
2.14
0.93
10.27
1.97
13C NMR (75 MHz, CDCl3):
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm
14.128
16.987
25.051
29.047
30.952
40.539
52.421
60.618
67.862
76.744
77.167
77.590
126.873
128.404
128.703
129.057
130.066
130.675
135.992
138.976
140.261
143.487
146.001
163.914
209.758
O
Ph
Ph
COOEt
O
Ph
Ph
COOEt
Supplementary Material (ESI) for Chemical CommunicationsThis journal is (c) The Royal Society of Chemistry 2010