1-Hydroxy-4-(hydroxyphenylmethyl)-1-phenyl-3-hexanone (4c) (Table 10, entry 3).
Following typical procedure, the reaction of benzaldehyde (2a) (0.156 mL, 1.5 mmol, 3.0 equiv.) and 2-pentanone (1n) (0.053 mL, 0.50 mmol, 1.0 equiv.) gave product 4c (129.7 mg, 87% yield, dr
= 90:10, 95% ee).
TLC: Rf 0.26 (hex/EtOAc = 2:1, stained orange with anisaldehyde) [α]D
31 +53.0 (c 1.10, CHCl3) for 95% ee.
1H NMR (CDCl3): δ 0.82 (t, 3H, J = 7.2 Hz), 1.55-1.82 (m, 2H), 2.61 (brs, 1H), 2.68-2.70 (m, 2H), 2.76-2.81 (m, 1H), 3.08 (brs, 1H), 4.93 (d, 1H, J = 6.0 Hz), 5.06 (dd, 1H, J = 6.0, 6.4 Hz), 7.15-7.46 (m, 10H).
13C NMR (CDCl3): δ 12.1, 19.9, 52.8, 61.3, 69.6, 73.6, 125.6, 126.1, 127.6, 127.7, 128.40, 128.42, 141.7, 142.6, 214.5.
IR (film): 1576, 1653, 1701, 3421 cm-1.
LRMS (Fab): m/z 321 (M+Na)+; HRMS (Fab): Calcd for C19H22O3Na 321.1467, found 321.1468.
The enantiomeric excess was determined to be 95% ee by chiral HPLC with Daicel Chiralcel OD-H column [eluent: hex/IPA = 19:1; flow rate: 1.0 mL/min; detection: 254 nm; tR: 35.3 min (minor), 47.1 min (major)].
O
+ PhCHO
(S)-BINAPO (10 mol %) SiCl4 (4 eq)
Cy2NMe (5 eq) CH2Cl2/EtCN,–60 ˚C 24 h
O
Ph OH Ph
OH
Et Et
1n 2a 4c
(3.0 eq)
実験の部 第２章
78
1-Hydroxy-4-(hydroxyphenylmethyl)-1-phenyl-3-heptanone (4d) (Table 10, entry 4).
Following typical procedure, the reaction of benzaldehyde (2a) (0.156 mL, 1.5 mmol, 3.0 equiv.) and 2-hexanone (1o) (0.062 mL, 0.50 mmol, 1.0 equiv.) gave product 4d (134.8 mg, 86% yield, dr
= 89:11, 94% ee).
TLC: Rf 0.29 (hex/EtOAc = 2:1, stained orange with anisaldehyde).
[α]D
29 +55.6 (c 0.88, CHCl3) for 94% ee.
1H NMR (CDCl3): δ 0.82 (t, 3H, J = 7.3 Hz), 1.01-1.13 (m, 1H), 1.15-1.30 (m, 1H), 1.62-1.73 (m, 1H), 1.73-1.80 (m, 1H), 2.62-2.70 (m, 3H), 2.85-2.95 (m, 1H), 3.12 (d, 1H, J = 3.2 Hz), 4.93 (dd, 1H, J = 2.8, 5.6 Hz), 5.06 (ddd, 1 H, J = 3.2, 5.2, 7.2 Hz), 7.15-7.46 (m, 10H).
13C NMR (CDCl3): δ 14.2, 21.0, 29.0, 52.8, 59.7, 69.7, 73.9, 125.6, 126.2, 127.7, 127.8, 128.5, 128.7, 141.6, 142.6, 214.9.
IR (film): 1703, 3412 cm-1.
LRMS (Fab): m/z 335 (M+Na)+; HRMS (Fab): Calcd for C20H24O3Na 335.1623, found 335.1617.
The enantiomeric excess was determined to be 94% ee by chiral HPLC with Daicel Chiralpak AD-H column [eluent: hex/IPA = 19:1; flow rate: 1.0 mL/min; detection: 254 nm; tR: 49.4 min (major), 61.1 min (minor)].
2-Benzyl-1,5-dihydroxy-1,5-diphenyl-3-pentanone (4e) (Table 10, entry 5).
Following typical procedure, the reaction of benzaldehyde (2a) (0.156 mL, 1.5 mmol, 3.0 equiv.) and benzylacetone (1p) (74.1 mg, 0.50 mmol, 1.0 equiv.) gave product 4e (124.3 mg, 69% yield, dr
= 89:11, 79% ee).
TLC: Rf 0.26 (hex/EtOAc = 2:1, stained orange with anisaldehyde).
[α]D
30 +58.8 (c 1.02, CHCl3) for 79% ee.
1H NMR (CDCl3): δ 2.03 (dd, 1H, J = 2.8, 18.0 Hz), 2.27 (dd, 1H, J = 9.6, 18.0 Hz), 2.83 (d, 1H, J
= 2.4 Hz), 2.95-3.08 (m, 3H), 3.19 (ddd, 1H, J = 2.8, 9.6, 9.6 Hz), 4.72 (d, 1H, J = 9.6 Hz), 5.03 (dd, 1H, J = 2.4, 5.6 Hz), 6.96-7.39 (m, 15H).
O
+ PhCHO
(S)-BINAPO (10 mol %) SiCl4 (4 eq)
Cy2NMe (5 eq) CH2Cl2/EtCN,–60 ˚C 24 h
O
Ph OH Ph
OH
nPr
nPr
1o 2a 4d
(3.0 eq)
O
+ PhCHO
(S)-BINAPO (10 mol %) SiCl4 (4 eq)
Cy2NMe (5 eq) CH2Cl2/EtCN,–60 ˚C 24 h
O
Ph OH Ph
OH
1p
4e 2a
(3.0 eq) Ph
Ph
実験の部 第２章
79
13C NMR (CDCl3): δ 33.7, 54.0, 61.9, 69.2, 73.7, 125.3, 126.1, 126.5, 127.4, 128.0, 128.3, 128.6, 128.7, 128.8, 139.0, 141.3, 142.3, 215.2.
IR (CHCl3): 1602, 1701, 3421 cm-1.
LRMS (Fab): m/z 383 (M+Na)+; HRMS (Fab): Calcd for C24H24O3Na 383.1623, found 383.1631.
The enantiomeric excess was determined to be 79% ee by chiral HPLC with Daicel Chiralcel OD-H column [eluent: hex/IPA = 19:1; flow rate: 1.0 mL/min; detection: 254 nm; tR: 17.0 min (minor), 26.0 min (major)].
1-Hydroxy-4-(hydroxyphenylmethyl)-7-methyl-1-phenyl-6-octen-3-one (4f) (Table 10, entry 6).
Following typical procedure, the reaction of benzaldehyde (2a) (0.156 mL, 1.50 mmol, 3.0 equiv.) and 2-methyl-2-hepten-6-one (1q) (0.074 mL, 0.50 mmol, 1.0 equiv.) gave product 4f (141.8 mg, 84% yield, dr = 89:11, 92% ee).
TLC: Rf 0.23 (hex/EtOAc = 4:1, stained orange with anisaldehyde).
[α]D
30 +46.6 (c 0.95, CHCl3) for 92% ee.
1H NMR (CDCl3): δ 1.51 (s, 3H), 1.63 (s, 3H), 2.22-2.32 (m, 1H), 2.41-2.53 (m, 1H), 2.61 (dd, 1H, J = 8.8, 18.0 Hz), 2.69 (dd, 1H, J = 3.6, 18.0 Hz), 2.78 (d, 1H, J = 2.4 Hz), 2.87-2.93 (m, 1H), 3.11 (d, 1H, J = 3.2 Hz), 4.95-5.02 (m, 3H), 7.23-7.37 (m, 10H).
13C NMR (CDCl3): δ 17.5, 25.6, 25.7, 53.0, 59.6, 69.6, 73.4, 120.9, 125.5, 126.1, 127.5, 127.6, 128.3, 128.4, 134.0, 141.5, 142.6, 214.8.
IR (CHCl3): 1494, 1701, 3419 cm-1.
LRMS (Fab): m/z 361 (M+Na)+; HRMS (Fab): Calcd for C22H26O3Na 361.1780, found 361.1780.
The enantiomeric excess was determined to be 92% ee by chiral HPLC with Daicel Chiralpak AS-H column [eluent: hex/IPA = 19:1; flow rate: 1.0 mL/min; detection: 254 nm; tR: 38.6 min (major), 48.1 min (minor)].
O
+ PhCHO
(S)-BINAPO (10 mol %) SiCl4 (4 eq)
Cy2NMe (5 eq) CH2Cl2/EtCN,–60 ˚C 24 h
O
Ph OH Ph
OH
1q
4f 2a
(3.0 eq)
実験の部 第２章
80
Ethyl 7-hydroxy-4-(hydroxyphenylmethyl)-5-oxo-7-phenylheptanoate (4g) (Table 10, entry 7).
Following typical procedure, the reaction of benzaldehyde (2a) (0.094 mL, 0.90 mmol, 3.0 equiv.) and ethyl 5-oxohexanoate (1r) (47.4 mg, 0.30 mmol, 1.0 equiv.) gave product 4g (72.2 mg, 65%
yield, dr = 90:10, 94% ee) and 4g’ (15.6 mg, 15% yield, single diastereomer, 94% ee).
TLC: Rf 0.26 (hex/EtOAc = 2:1, stained blue with anisaldehyde).
[α]D 30
+34.9 (c 0.99, CHCl3) for 94% ee.
1H NMR (CDCl3): δ 1.22 (t, 3H, J = 6.9 Hz), 1.72-2.22 (m, 3H), 2.70-2.78 (m, 2H), 2.98-3.05 (m, 1H), 2.62-2.73 (m, 2H), 4.07 (q, 2H, J = 6.9 Hz), 4.98 (d, 1H, J = 6.0 Hz), 5.08 (dd, 1H, J = 5.2, 7.2 Hz), 7.20-7.38 (m, 10H).
13C NMR (CDCl3): δ 14.1, 21.6, 31.9, 52.3, 58.5, 60.5, 69.8, 73.5, 125.6, 126.1, 126.4, 127.7, 127.9, 128.4, 141.3, 142.6, 173.2, 213.2.
IR (film): 1494, 1604, 1713, 1740, 3458 cm-1.
LRMS (Fab): m/z 393 (M+Na)+; HRMS (Fab): Calcd for C22H26O5Na 393.1678, found 393.1695.
The enantiomeric excess was determined to be 94% ee by chiral HPLC with Daicel Chiralpak AD-H column [eluent: hex/IPA = 9:1; flow rate: 1.0 mL/min; detection: 254 nm; tR: 22.4 min (minor), 28.0 min (major)].
4-(3-hydroxy-3-phenyl-1-oxopropyl)-5-phenyl-2H-pyran-2-one (4g’) TLC: Rf 0.15 (hex/EtOAc = 2:1, stained blue with anisaldehyde).
[α]D
16 –4.0 (c 1.12, CHCl3) for 94% ee.
1H NMR (CDCl3): δ 2.02-2.28 (m, 2H), 2.42 (dd, 1H, J = 8.1, 17.6 Hz), 2.58-2.66 (m, 3H), 2.74-2.82 (m, 2H), 3.12-3.19 (m, 1H), 4.98 (dd, 1H, J = 8.1, 9.0 Hz), 5.45 (d, 1H, J = 9.6 Hz), 7.17-7.42 (m, 10H).
13C NMR (CDCl3): δ 22.2, 28.3, 52.4, 52.8, 70.0, 81.7, 125.5, 126.7, 127.9, 128.6, 128.9, 129.1, 137.3, 142.2, 170.3, 209.7.
IR (CHCl3): 1711, 1733, 3446 cm-1.
LRMS (Fab): m/z 347 (M+Na)+; HRMS (Fab): Calcd for C20H20O4Na 347.1259, found 347.1259.
The enantiomeric excess was determined to be 94% ee by chiral HPLC with Daicel Chiralcel OD-H column [eluent: hex/IPA = 4:1; flow rate: 1.0 mL/min; detection: 254 nm; tR: 15.6 min (major), 19.5 min (minor)].
O
+ PhCHO
(S)-BINAPO (10 mol %) SiCl4 (4 eq)
Cy2NMe (5 eq) CH2Cl2/EtCN,–60 ˚C 24 h
O
Ph OH Ph
OH
1r
4g 2a
(3.0 eq) EtO
O
O EtO
O
Ph OH O
Ph
O +
4g'
実験の部 第２章
81
1,7-Diphenyl-1-hydroxy-4-(hydroxyphenylmethyl)-3,7-heptanedione (4h) (Table 10, entry 8).
Following typical procedure, the reaction of benzaldehyde (2a) (0.078 mL, 0.75 mmol, 3.0 equiv.) and 1-phenyl-1,5-hexanxedione (1s) (47.6 mg, 0.25 mmol, 1.0 equiv.) gave product 4h (67.4 mg, 67% yield, dr = 90:10, 81% ee).
TLC: Rf 0.27 (hex/EtOAc = 2:1, stained purple with anisaldehyde).
[α]D
23 +48.3 (c 0.80, CHCl3) for 81% ee.
1H NMR (CDCl3): δ 2.00-2.11 (m, 1H), 2.12-2.23 (m, 1H), 2.71-3.06 (m, 7H), 5.04 (dd, 1H, J = 2.8, 5.6 Hz), 5.09-5.14 (m, 1H), 7.23-7.57 (m, 13H), 7.83 (d, 2H, J = 6.0 Hz).
13C NMR (CDCl3): δ 20.7, 35.9, 51.9, 58.5, 70.0, 73.4, 125.6, 126.1, 127.7, 127.9, 128.0, 128.51, 128.54, 128.6, 133.2, 136.5, 141.4, 142.6, 200.0, 213.6.
IR (film): 1683, 1703, 3446 cm-1.
LRMS (Fab): m/z 425 (M+Na)+; HRMS (Fab): Calcd for C26H26O4Na 425.1729, found 425.1736.
The enantiomeric excess was determined to be 81% ee by chiral HPLC with Daicel Chiralcel OZ-H column [eluent: hex/IPA = 6:1; flow rate: 1.0 mL/min; detection: 254 nm; tR: 33.4 min (minor), 55.6 min (major)].
1-(4-Bromophenyl)-1-hydroxy-4-[hydroxy(4-bromophenyl)methyl]-3-hexanone (4j) (Table 11, entry 2).
Following typical procedure, the reaction of p-bromobenzaldehyde (2c) (278 mg, 1.5 mmol, 3.0 equiv.) and 2-pentanone (1n) (0.053 mL, 0.50 mmol, 1.0 equiv.) gave product 4j (203.3 mg, 89%
yield, dr = 90:10, 92% ee).
TLC: Rf 0.30 (hex/EtOAc = 2:1, stained orange with anisaldehyde).
[α]D
26 +34.3 (c 1.12, CHCl3) for 92% ee.
1H NMR (CDCl3): δ 0.81 (t, 3H, J = 8.0 Hz), 1.58-1.63 (m, 1H), 1.73 (ddd, 1H, J = 1.6, 7.2, 8.0 Hz), 2.68-2.71 (m, 3H), 2.76 (ddd, 1H, J = 3.2, 4.4, 5.6 Hz), 3.17 (d, 1H, J = 3.2 Hz), 4.92 (d, 1H, J =
O
+ PhCHO
(S)-BINAPO (10 mol %) SiCl4 (4 eq)
Cy2NMe (5 eq) CH2Cl2/EtCN,–60 ˚C 48 h
O
Ph OH Ph
OH
1s
4h 2a
(3.0 eq) Ph
O
O Ph
Me
O +
(S)-BINAPO (10 mol%) SiCl4 (4 eq)
Cy2NMe (5 eq) CH2Cl2/EtCN, –40 ˚C 24 h
O OH
1n
(3.0 eq) 4j
Et OH Et
CHO
Br
2c Br Br
実験の部 第２章
82
3.6 Hz), 5.04 (ddd, 1H, J = 2.4, 3.6, 6.0 Hz), 7.14-7.19 (m, 4H), 7.44-7.48 (m, 4H).
13C NMR (CDCl3): δ 12.1, 19.7, 52.6, 60.8, 69.1, 72.9, 121.5, 121.6, 127.3, 127.8, 131.5, 131.6, 140.6, 141.6, 214.2.
IR (film): 1522, 1540, 1558, 1683, 3440 cm-1.
LRMS (Fab): m/z 477, 479, 481 (M+Na)+; HRMS (Fab): Calcd for C19H20Br2O3Na 476.9677, found 476.9683.
The enantiomeric excess was determined to be 92% ee by chiral HPLC with Daicel Chiralpak AD-3 column [eluent: hex/IPA = 4:1; flow rate: 0.5 mL/min; detection: 254 nm; tR: 26.7 min (major), 32.0 min (minor)].
1-Hydroxy-4-[hydroxy(4-methoxyphenyl)methyl]-1-(4-methoxyphenyl)-3-hexanone (4k) (Table 12, entry 3).
Following typical procedure, the reaction of p-anisaldehyde (2g) (0.182 mL, 1.5 mmol, 3.0 equiv.) and 2-pentanone (1n) (0.053 mL, 0.50 mmol, 1.0 equiv.) gave product 4k (117.4 mg, 66% yield, dr
= 92:8, 98% ee).
TLC: Rf 0.20 (hex/EtOAc = 2:1, stained blue with anisaldehyde).
[α]D
29 +35.3 (c 1.13, CHCl3) for 98% ee.
1H NMR (CDCl3): for major isomer δ 0.83 (t, 3H, J = 7.6 Hz), 1.52-1.80 (m, 3H), 2.50 (brs, 1H), 2.66 (d, 2H, J = 6.4 Hz), 2.75-2.82 (m, 1H), 3.08 (brs, 1H), 3.78 (s, 3H), 3.81 (s, 3H), 4.87 (d, 1H, J
= 6.0 Hz), 5.00 (dd, 1H, J = 6.0, 6.4 Hz), 6.85 (d, 2H, J = 8.6 Hz), 6.88 (d, 2H, J = 8.6 Hz), 7.19 (d, 2H, J = 8.8 Hz), 7.22 (d, 2H, J = 8.4 Hz).
13C NMR (CDCl3): δ 12.0, 20.3, 52.7, 55.2, 55.8, 61.4, 69.2, 73.4, 113.7, 113.8, 126.9, 127.4, 133.9, 134.3, 158.96, 159.03, 214.5.
IR (film): 1701, 3446 cm-1
LRMS (Fab): m/z 381 (M+Na)+; HRMS (Fab): Calcd for C21H26O5Na 381.1678, found 361.1675.
The enantiomeric excess was determined to be 98% ee by chiral HPLC with Daicel Chiralcel OD-3 column [eluent: hex/IPA = 6:1; flow rate: 1.0 mL/min; detection: 254 nm; tR: 19.4 min (major), 34.0 min (minor)].
Me
O +
(S)-BINAPO (10 mol%) SiCl4 (4 eq)
Cy2NMe (5 eq) CH2Cl2/EtCN, –40 ˚C 24 h
O OH
1n
(3.0 eq) 4k
Et OH Et
CHO
MeO
2g MeO OMe
実験の部 第２章
83
1-Hydroxy-4-[hydroxy(4-methylphenyl)methyl]- 1-(4-Methylphenyl)-3-hexanone (4l) (Table 11, entry 4).
Following typical procedure, the reaction of p-tolualdehyde (2b) (0.177 mL, 1.5 mmol, 3.0 equiv.) and 2-pentanone (1n) (0.053 mL, 0.50 mmol, 1.0 equiv.) gave product 4l (107.4 mg, 76% yield, dr
= 91:9, 97% ee).
TLC: Rf 0.31 (hex/EtOAc = 2:1, stained orange with anisaldehyde).
[α]D
29 +34.8 (c 1.65, CHCl3) for 97% ee.
1H NMR (CDCl3): δ 0.81 (t, 3H, J = 7.6 Hz), 1.63-1.82 (m, 2H), 2.33 (s, 3H), 2.34 (s, 3H), 2.50 (d, 1H, J = 3.2 Hz), 2.66-2.69 (m, 2H), 2.80 (ddd, 1H, J = 6.0, 4.4, 9.6 Hz), 3.07 (d, 1H, J = 3.2 Hz), 4.89 (dd, 1H, J = 3.2, 6.0 Hz), 5.02 (ddd, 1H, J = 3.2, 5.6, 6.4 Hz), 7.11-7.19 (m, 8H).
13C NMR (CDCl3): δ 12.1, 20.1, 21.05, 21.08, 52.7, 61.4, 69.5, 73.6, 125.6, 126.1, 129.1, 129.2, 137.3, 137.5, 138.70, 138.72, 214.8.
IR (film): 1701, 3421 cm-1.
LRMS (Fab): m/z 349 (M+Na)+; HRMS (Fab): Calcd for C21H26O3Na 349.1780, found 349.1843.
The enantiomeric excess was determined to be 98% ee by chiral HPLC with Daicel Chiralcel OD-3 column [eluent: hex/IPA = 9:1; flow rate: 1.0 mL/min; detection: 254 nm; tR: 17.2 min (minor), 19.7 min (major)].
1-(3,5-Dimethylphenyl)-1-hydroxy-4-[hydroxy(3,5-dimethylphenyl)methyl]-3-hexanone (4m) (Table 11, entry 5).
Following typical procedure, the reaction of 3,5-dimethylbenzaldehyde (2i) (0.201 mL, 1.5 mmol, 3.0 equiv.) and 2-pentanone (1n) (0.053 mL, 0.50 mmol, 1.0 equiv.) gave product 4m (125.8 mg, 72% yield, dr =92:8, 91% ee).
TLC: Rf 0.30 (hex/EtOAc = 4:1, stained orange with anisaldehyde) [α]D
24 +33.9 (c 1.02, CHCl3) for 91% ee.
Me
O +
(S)-BINAPO (10 mol%) SiCl4 (4 eq)
Cy2NMe (5 eq) CH2Cl2/EtCN, –40 ˚C 24 h
O OH
1n
(3.0 eq) 4l
Et OH Et
CHO
Me
2b Me Me
Me
O +
(S)-BINAPO (10 mol%) SiCl4 (4 eq)
Cy2NMe (5 eq) CH2Cl2/EtCN, –40 ˚C 24 h
O OH
1n
(3.0 eq) 4m
Et OH Et
CHO
2i Me
Me
Me
Me Me
Me
実験の部 第２章
84
1H NMR (CDCl3): δ 0.84 (t, 3H, J = 7.6 Hz), 1.64-1.70 (m, 1H), 1.73-1.82 (m, 1H), 2.30 (s, 6H), 2.32 (s, 6H), 2.53 (brs, 1H), 2.66-2.69 (m, 2H), 2.77-2.82 (m, 1H), 3.06 (brs, 1H), 4.86 (d, 1H, J = 5.2 Hz), 5.00 (dd, 1H, J = 4.4. 8.0 Hz), 6.85-6.95 (m, 6H).
13C NMR (CDCl3): δ 12.2, 20.0, 21.28, 21.34, 52.8, 61.3, 69.6, 73.8, 123.3, 123.9, 129.3, 129.4, 138.0, 138.1, 141.6, 142.5, 215.1.
IR (film): 1701, 3421 cm-1.
LRMS (Fab): m/z 377 (M+Na)+; HRMS (Fab): Calcd for C23H30O3Na 377.2093, found 377.2122.
The enantiomeric excess was determined to be 91% ee by chiral HPLC with Daicel Chiralpak AD-3 column [eluent: hex/IPA = 19:1; flow rate: 1.0 mL/min; detection: 254 nm; tR: 33.5 min (minor), 56.3 min (major)].
1-Hydroxy-4-[hydroxy(4-nitrophenyl)methyl]-1-(4-nitrophenyl)-3-hexanone (4n) (Table 11, entry 6).
Following typical procedure, the reaction of p-nitrobenzaldehyde (2j) (226.7 mg, 1.5 mmol, 3.0 equiv.) and 2-pentanone (1n) (0.053 mL, 0.5 mmol, 1.0 equiv.) gave product 4n (108.9 mg = 56%
yield, dr = 92:8, 80% ee).
TLC: Rf 0.22 (hex/EtOAc = 2:1, stained orange with anisaldehyde) [α]D
29 +42.6 (c 1.20, CHCl3).
1H NMR (CDCl3) δ 0.81 (t, 3H, J = 7.6 Hz), 1.63-1.82 (m, 2H), 2.65 (d, 2H, J = 5.6, 6.0 Hz), 2.72-2.89 (m, 3H), 3.00 (brs, 1H), 3.23 (brs, 1H), 5.14 (d, 1H, J = 4.4 Hz), 5.27 (dd, 1H, J = 5.6, 8.0 Hz), 7.43-7.58 (m, 4H), 8.17-8.23 (m, 4H).
13C NMR (CDCl3): δ 12.1, 19.2, 25.2, 52.4, 60.3, 72.3, 123.5, 123.7, 126.4, 127.0, 147.19, 147.21, 149.0, 150.0, 213.3.
IR (film): 1346, 1517, 1683, 3446 cm-1. LRMS: decomposed during analysis.
The enantiomeric excess was determined to be 98% ee by chiral HPLC with Daicel Chiralcel AD-H column [eluent: hex/IPA = 6:1; flow rate: 1.0 mL/min; detection: 254 nm; tR: 41.4 min (major), 50.5 min (minor)].
Me
O +
(S)-BINAPO (10 mol%) SiCl4 (4 eq)
Cy2NMe (5 eq) CH2Cl2/EtCN, –40 ˚C 24 h
O OH
1n
(3.0 eq) 4n
Et OH Et
CHO
O2N
2j O2N NO2
実験の部 第２章
85
1-Hydroxy-4-[hydroxy(2-naphthyl)methyl]-1-(2-naphthyl)-3-hexanone (4o) (Table 11, entry 7).
Following typical procedure, the reaction of 2-naphthaldehyde (2d) (234 mg, 1.5 mmol, 3.0 equiv.) and 2-pentanone (1n) (0.053 mL, 0.50 mmol, 1.0 equiv.) gave product 4o (154.6 mg, 78% yield, dr
= 90:10, 93% ee).
TLC: Rf 0.31 (hex/EtOAc = 2:1, stained orange with anisaldehyde).
[α]D
30 +40.8 (c 0.99, CHCl3) for 93% ee.
1H NMR (CDCl3): δ 0.84 (t, 3H, J = 8.0 Hz), 1.69-1.75 (m, 1H), 1.75-1.82 (m, 1H), 2.78 (d, 1H, J = 4.4 Hz), 2.81-2.85 (m, 2H), 2.94-2.98 (m, 1H), 3.21 (d, 1H, J = 2.8 Hz), 5.16 (dd, 1H, J = 2.8, 4.8 Hz), 5.25 (ddd, 1H, J = 3.2, 1.5, 7.2 Hz), 7.28-7.52 (m, 6H), 7.70-7.88 (m, 8H).
13C NMR (CDCl3): δ 12.1, 19.6, 52.3, 61.0, 69.8, 73.5, 123.6, 123.9, 124.3, 125.1, 125.8, 125.9, 126.1, 126.2, 127.55, 127.58, 127.9, 128.0, 128.1, 128.2, 128.3, 132.8, 133.05, 133.12, 139.0, 140.0, 214.3.
IR (film): 1701, 3421, 3446 cm-1.
LRMS (Fab): m/z 421 (M+Na)+; HRMS (Fab): Calcd for C27H26O3Na 421.1780, found 421.1707.
The enantiomeric excess was determined to be 93% ee by chiral HPLC with Daicel Chiralpak AD-3 column [eluent: hex/IPA = 3:1; flow rate: 1.0 mL/min; detection: 254 nm; tR: 31.8 min (minor), 37.0 min (major)].
1-Hydroxy-4-[hydroxy(1-naphthyl)methyl]-1-(1-naphthyl)-3-hexanone (4p) (Table 11, entry 8).
Following typical procedure, the reaction of 1-naphthaldehyde (2k) (0.204 mL, 1.5 mmol, 3.0 equiv.) and 2-pentanone (1n) (0.053 mL, 0.50 mmol, 1.0 equiv.) gave product 4p (115.7 mg, 58%
yield, dr = 89:11, 93% ee).
TLC: Rf 0.32 (hex/EtOAc = 2:1, stained orange with anisaldehyde).
Me
O +
(S)-BINAPO (10 mol%) SiCl4 (4 eq)
Cy2NMe (5 eq) CH2Cl2/EtCN, –40 ˚C 24 h
O OH
1n
(3.0 eq) 4o
Et OH Et
CHO
2d
Me
O +
(S)-BINAPO (10 mol%) SiCl4 (4 eq)
Cy2NMe (5 eq) CH2Cl2/EtCN, –40 ˚C 24 h
O OH
1n
(3.0 eq) 4p
Et OH Et
CHO
2k
実験の部 第２章
86 [α]D
27 +70.3 (c 1.32, CHCl3) for 93% ee.
1H NMR (CDCl3): δ 0.76 (t, 3H, J = 7.6 Hz), 1.58-1.64 (m, 1H), 1.82-1.96 (m, 1H), 2.85-3.05 (m, 3H), 3.06-3.10 (m, 1H), 3.20 (d, 1H, J = 2.8 Hz), 5.80 (dd, 1H, J = 2.8, 3.6 Hz), 5.91 (dd, 1H, J = 3.6, 2.8 Hz), 7.42-7.96 (m, 14H).
13C NMR (CDCl3): δ 12.3, 19.3, 23.0, 51.8, 59.5, 67.1, 70.0, 122.6, 122.7, 122.9, 124.4, 125.3, 125.46, 125.53, 125.6, 126.22, 126.25, 128.1, 128.3, 129.0, 129.1, 129.7, 129.8, 133.7, 133.8, 136.6, 138.1, 215.7.
IR (film): 1597, 1702, 3398 cm-1.
LRMS (Fab): m/z 421 (M+Na)+; HRMS (Fab): Calcd for C27H26O3Na 421.1780, found 421.1805.
The enantiomeric excess was determined to be 93% ee by chiral HPLC with Daicel Chiralpak AD-3 columns [eluent: hex/IPA = 9:1; flow rate: 1.0 mL/min; detection: 254 nm; tR: 49.2 min (minor), 56.5 min (major)].
1-(2-Furyl)-1-hydroxy-4-[hydroxy(2-furyl)methyl]-3-hexanone (4q) (Table 11, entry 9).
Following typical procedure, the reaction of furfural (2e) (0.124 mL, 1.5 mmol, 3.0 equiv.) and 2-pentanone (1n) (0.053 mL, 0.50 mmol, 1.0 equiv.) gave product 4q (74.1 mg, 65% yield, dr = 90:10, 88% ee).
TLC: Rf 0.23 (hex/EtOAc = 2:1, stained blue with anisaldehyde).
[α]D
29 +21.0 (c 1.05, CHCl3) for 88% ee.
1H NMR (CDCl3): δ 0.89 (t, 3H, J = 7.2 Hz), 1.71-1.88 (m, 2H), 2.48 (d, 1H, J = 4.8 Hz), 2.88 (dd, 1H, J = 3.6, 18.0 Hz), 3.04 (dd, 1H, J = 8.8, 18.0 Hz), 3.03-3.06 (m, 1H), 3.08 (d, 1H, J = 4.0 Hz), 4.96 (dd, 1H, J = 4.8, 6.4 Hz), 5.13 (ddd, 1H, J = 3.6, 8.8, 4.0 Hz), 6.24 (d, 1H, J = 3.2 Hz), 6.26 (d, 1H, J = 3.2 Hz), 6.31 (dd, 1H, J = 3.2, 2.0 Hz), 6.34 (dd, 1H, J = 3.2, 1.6 Hz), 7.36 (d, 1H, J = 2.0 Hz), 7.37 (d, 1H, J = 1.6 Hz).
13C NMR (CDCl3): δ 11.7, 20.3, 48.1, 58.5, 63.4, 67.7, 106.3, 107.1, 110.2, 110.4, 141.9, 142.0, 154.2, 154.8, 212.6.
IR (film): 1701, 3419 cm-1.
LRMS (Fab): m/z 301 (M+Na)+; HRMS (Fab): Calcd for C15H18O5Na 301.1052, found 301.1042.
The enantiomeric excess was determined to be 88% ee by chiral HPLC with Daicel Chiralpak AD-3 column [eluent: hex/IPA = 9:1; flow rate: 1.0 mL/min; detection: 220 nm; tR: 31.6 min (major), 34.3
Me
O +
(S)-BINAPO (10 mol%) SiCl4 (4 eq)
Cy2NMe (5 eq) CH2Cl2/EtCN, –40 ˚C 24 h
O OH
1n
(3.0 eq) 4q
Et OH Et
CHO
2e
O O O
実験の部 第２章
87 min (minor)].
1-Hydroxy-4-[hydroxy(2-thienyl)methyl]-1-(2-thienyl)-3-hexanone (4r) (Table 11, entry 10).
Following typical procedure, the reaction of 2-thiophenecarboxyaldehyde (2l) (0.138 mL, 1.5 mmol, 3.0 equiv.) and 2-pentanone (1n) (0.053 mL, 0.50 mmol, 1.0 equiv.) gave product 4r (109.3 mg, 71% yield, dr = 92:8, 95% ee).
TLC: Rf 0.24 (hex/EtOAc = 2:1, stained blue with anisaldehyde).
[α]D
23 +8.8 (c 1.56, CHCl3) for 95% ee.
1H NMR (CDCl3): δ 0.89 (t, 3H, J = 7.6 Hz), 1.75-1.88 (m, 2H), 2.60 (d, 1H, J = 3.2 Hz), 2.85-2.89 (m, 2H), 2.91-2.95 (m, 1H), 3.23 (d, 1H, J = 4.0 Hz), 5.19 (dd, 1H, J = 4.0, 6.4 Hz), 5.30-5.36 (m 1H), 6.24 (d, 1H, J = 3.2 Hz), 6.26 (d, 1H, J = 3.2 Hz), 6.31 (dd, 1H, J = 3.2, 2.0 Hz), 6.34 (dd, 1H, J = 3.2, 1.6 Hz), 6.88-7.03 (m, 4H), 7.21-7.29 (m, 2H).
13C NMR (CDCl3): δ 11.8, 20.8, 52.4, 61.5, 65.7, 69.9, 123.6, 124.4, 124.6, 124.8, 126.6, 126.8, 145.6, 146.3, 213.1.
IR (film): 1702, 3406 cm-1.
LRMS (Fab): m/z 333 (M+Na)+; HRMS (Fab): Calcd for C15H18O3S2Na 333.0595, found 333.0601.
The enantiomeric excess was determined to be 95% ee by chiral HPLC with Daicel Chiralcel OZ-H column [eluent: hex/IPA = 19:1; flow rate: 1.0 mL/min; detection: 220 nm; tR: 53.4 min (minor), 57.9 min (major)].
Me
O +
(S)-BINAPO (10 mol%) SiCl4 (4 eq)
Cy2NMe (5 eq) CH2Cl2/EtCN, –40 ˚C 24 h
O OH
1n
(3.0 eq) 4r
Et OH Et
CHO
2l
S S S
実験の部 第２章
88 Chapter 2. Section 4.
Typical Procedure for Chapter 2, Section 5.
Double Aldol Reaction of Isopropyl Methyl Ketone (1u) and Benzaldehyde (2a). (Scheme 48)
1,5-Dihydroxy-1,5-dipenyl-2,2-dimethyl-3-pentanone (linear-6a)
5-Hydroxy-4-(hydroxyphenylmethyl)-2-methyl-5-phenyl-3-pentanone (branched-6a)
Silicon tetrachloride (0.23 mL, 2.0 mmol, 4.0 eq) was added dropwise to the solution of benzaldehyde (2a) (0.156 mL, 1.5 mmol, 3.0 equiv), 3-methyl-2-butanone (1u) (0.054 mL, 0.50 mmol, 1.0 equiv), dicyclohexylmethylamine (0.54 mL, 2.5 mmol, 5.0 equiv), and (S)-BINAPO (32.7 mg, 0.050 mmol, 10 mol %) in CH2Cl2 (5.0 mL) at –40 ˚C. After being stirred for 24 h, the reaction was quenched with sat. NaHCO3 (5 mL) and then the slurry was stirred for 0.5 h. The two-layers mixture was filtered through a celite pad and the aqueous layer was extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with 10% HCl (20 mL), sat.
NaHCO3 (20 mL), and brine (20 mL), and then dried over Na2SO4. After filtration and concentration, the obtained crude product was purified by column chromatography (hexane/EtOAc
= 3:1, SiO2: 10 g) to give double aldol adduct 6a as a regioisomeric mixture (119.2 mg, 80% yield, linear:branched = 1:1.5).
Data for regioisomeric mixture (linear:branched = 1.5:1)
TLC: Rf 0.22 (hex/EtOAc = 4:1, stained blue with anisaldehyde).
[α]D
16 +39.4 (c 1.12, CHCl3) for regioisomeric mixture.
1H NMR (CDCl3) δ 0.26 (d, 1.8H, J = 7.3 Hz, branched), 0.34 (d, 1.8H, J = 6.9 Hz, branched), 1.00 (s, 1.2H, linear), 1.06 (s, 1.2H, linear), 1.46 (qq, 0.6H, J = 6.9, 7.3 Hz, branched), 2.83 (dd, 0.4H, J
= 2.3, 17.4 Hz, linear), 3.07 (dd, 0.4H, J = 9.6, 17.4 Hz, linear), 3.37 (dd, 0.6H, J = 2.7, 8.2 Hz, branched), 5.00 (s, 0.4H, linear), 5.18 (d, 0.6H, J = 8.2 Hz, branched), 5.23 (dd, 0.4H, J = 2.3, 9.6 Hz, linear), 5.32 (d, 0.6H, J = 2.7 Hz, branched), 7.28-7.40 (m, 10H).
13C NMR (CDCl3) for regioisomeric mixture: δ 15.9, 16.2, 17.2, 22.5, 42.8, 47.3, 52.8, 64.3, 70.2, 72.0, 73.0, 78.2, 125.2, 125.6, 126.4, 127.3, 127.6, 127.7, 127.8, 128.1, 128.28, 128.31, 128.5, 128.6, 139.7, 141.7, 142.3, 142.9, 216.3, 218.9.
IR (film): 1689, 1701, 3431 cm-1.
LRMS (Fab): m/z 321 (M+Na)+; HRMS (Fab): Calcd for C19H22O3Na 321.1467, found 321.1475.
O
+ PhCHO
(S)-BINAPO (10 mol %) SiCl4 (4 eq)
Cy2NMe (5 eq) CH2Cl2, –40 ˚C, 24 h
O
Ph OH
(3.0 eq) Ph
OH O
Ph Ph HO
OH +
linear-6a
(75% ee) branched-6a
(70% ee) 1u
実験の部 第２章
89
The enantiomeric excess was determined to be 75% ee (linear) and 70% ee (branched) by HPLC analysis with Daicel Chiralpak AS-H column [eluent: hex/IPA = 19:1; flow rate: 1.0 mL/min;
detection: 254 nm; tR: 16.3 min (linear-minor), 18.1 min (linear-major), 47.5 min (branched-major), 55.3 min (branched-minor)].
1-(Hydroxyphenylmethyl)-1-(1-oxo-3-hydroxy-3-phenylpropyl)-cyclobutane (linear-6b) 1-(Cyclobutyl)-3-hydroxy-2-(hydroxyphenylmethyl)-3-phenyl-1-propanone (branched-6b) (Table 12, entry 2).
Silicon tetrachloride (0.23 mL, 2.0 mmol, 4.0 eq) was added dropwise to the solution of benzaldehyde (2a) (0.156 mL, 1.5 mmol, 3.0 equiv), acetylcyclobutane (1v) (0.055 mL, 0.50 mmol, 1.0 equiv), dicyclohexylmethylamine (0.54 mL, 2.5 mmol, 5.0 equiv), and (S)-BINAPO (32.7 mg, 0.050 mmol, 10 mol %) in CH2Cl2 (5.0 mL) at –40 ˚C. After being stirred for 24 h, the reaction was quenched with sat. NaHCO3 (5 mL) and then the slurry was stirred for 0.5 h. The two-layers mixture was filtered through a celite pad and the aqueous layer was extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with 10% HCl (20 mL), sat. NaHCO3 (20 mL), and brine (20 mL), and then dried over Na2SO4. After filtration and concentration, the obtained crude product was purified by column chromatography (hexane/EtOAc = 3:1, SiO2: 10 g) to give double aldol adduct 6b as a regioisomeric mixture (85.4 mg, 55% yield, linear:branched = 2.2:1).
Data for regioisomeric mixture (linear:branched = 2.2:1)
TLC: Rf 0.15 (hex/EtOAc = 4:1, stained blue with anisaldehyde).
[α]D
16 +36.2 (c 1.08, CHCl3) for regioisomeric mixture.
1H NMR (CDCl3) δ 1.23-1.46 (m, 3H), 2.25-2.40 (m, 3.31H), 2.63 (dd, 0.69H, J = 2.9, 17.4 Hz, linear), 2.92 (dd, 0.69H, J = 17.4, 9.6 Hz, linear), 3.00 (brs, 0.31H, branched), 3.20 (dd, 0.31H, J = 2.8, 8.2 Hz, branched), 3.56-3.62 (m, 1.38H, linear), 4.50 (brs, 0.31H, branched), 4.96 (s, 0.69H, linear), 5.08 (dd, 0.69H, J = 9.6, 2.9 Hz, linear), 5.18 (d, 0.31H, J = 8.2 Hz, branched), 5.28 (m, 0.31H, linear), 7.28-7.40 (m, 10H).
13C NMR (CDCl3): δ 15.1, 16.8, 22.7, 23.0, 24.8, 27.4, 47.3, 47.8, 58.6, 63.8, 70.2, 71.8, 72.9, 76.8, 125.1, 125.5, 126.2, 126.8, 127.2, 127.6, 128.08, 128.11, 128.2, 128.3, 128.4, 128.6, 140.2, 141.7, 142.4, 142.8, 215.4, 215.9.
O
+ PhCHO
(S)-BINAPO (10 mol %) SiCl4 (4 eq)
Cy2NMe (5 eq)
O
Ph HO
Ph OH +
(2.2 eq) Ph
O OH
Ph OH
CH2Cl2, –60 ˚C, 24 h
linear-6b branched-6b
1v 2a
実験の部 第２章
90 IR (film): 1681, 1695, 3421 cm-1.
LRMS (Fab): m/z 333 (M+Na)+; HRMS (Fab): Calcd for C20H22O3 333.1467, found 333.1463.
The enantiomeric excess was determined to be 91% ee (linear) and 84% ee (branched) by HPLC analysis with Daicel Chiralpak AD-H column [eluent: hex/IPA = 92:8; flow rate: 1.0 mL/min;
detection: 254 nm; tR: 13.2 min (linear-minor), 14.6 min (linear-major), 34.2 min (branched-major), 70.3 min (branched-minor)].
1-(Hydroxyphenylmethyl)-1-(1-oxo-3-hydroxy-3-phenylpropyl)-cyclopentane (linear-6c) 1-(Cyclopenyl)-3-hydroxy-2-(hydroxyphenylmethyl)- 3-phenyl-1-propanone (branched-6c) (Table 12, entry 3).
Silicon tetrachloride (0.23 mL, 2.0 mmol, 4.0 eq) was added dropwise to the solution of benzaldehyde (2a) (0.156 mL, 1.5 mmol, 3.0 equiv), acetylcyclopentane (1w) (56.1 mg, 0.50 mmol, 1.0 equiv), dicyclohexylmethylamine (0.54 mL, 2.5 mmol, 5.0 equiv), and (S)-BINAPO (32.7 mg, 0.050 mmol, 10 mol %) in CH2Cl2 (5.0 mL) at –40 ˚C. After being stirred for 24 h, the reaction was quenched with sat. NaHCO3 (5 mL) and then the slurry was stirred for 0.5 h. The two-layers mixture was filtered through a celite pad and the aqueous layer was extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with 10% HCl (20 mL), sat. NaHCO3 (20 mL), and brine (20 mL), and then dried over Na2SO4. After filtration and concentration, the obtained crude product was purified by column chromatography (hexane/EtOAc = 3:1, SiO2: 10 g) to give double aldol adduct 6b as a regioisomeric mixture (71.4 mg, 44% yield, linear:branched = 1:0.65).
Data for regioisomeric mixture (linear:branched = 1:0.65) TLC: Rf 0.24 (hex/EtOAc = 4:1, stained blue with anisaldehyde).
[α]D
15 +35.7 (c 1.04, CHCl3) for a regioisomeric mixture.
1H NMR (CDCl3) δ 0.75-2.10 (m, 8.39H), 2.69 (dd, 0.61H, J = 2.7, 17.4 Hz, linear), 2.97 (dd, 0.61H, J = 17.4, 9.6 Hz, linear), 3.34 (dd, 0.39H, J = 2.3, 8.6 Hz, branched), 4.97 (s, 0.69H, linear), 5.15 (dd, 0.69H, J = 2.7, 9.6 Hz, linear), 5.23 (d, 0.39H, J = 2.3 Hz, branched), 5.31 (dd, 0.39H, J = 8.6 Hz, branched), 7.28-7.40 (m, 10H. ArH).
13C NMR (CDCl3): δ 24.5, 24.9, 25.4, 27.3, 27.4, 28.8, 48.2, 53.8, 65.4, 65.5, 70.4, 71.9, 73.0, 76.0, 77.2, 77.7, 125.2, 125.6, 126.3, 127.2, 127.4, 127.6, 127.9, 128.1, 128.26, 128.35, 128.44, 128.6,
O
+ PhCHO
(S)-BINAPO (10 mol %) SiCl4 (4 eq)
Cy2NMe (5 eq)
O
Ph HO
Ph OH +
(2.2 eq) Ph
O OH
Ph OH CH2Cl2
linear-6c branched-6c
1w 2a
実験の部 第２章
91 140.5, 141.7, 142.3, 142.9, 215.6, 218.0.
IR (film): 1693, 3431 cm-1.
LRMS (Fab): m/z 347 (M+Na)+; HRMS (Fab): Calcd for C21H24O3Na 347.1623, found 347.1564.
The enantiomeric excess was determined to be 85% ee (linear) and 83% ee (branched) by HPLC analysis with Daicel Chiralpak AD-H column [eluent: hex/IPA = 9:1; flow rate: 1.0 mL/min;
detection: 254 nm; tR: 10.8 min (linear-minor), 11.9 min (linear-major), 24.8 min (branched-major), 51.3 min (branched-minor)].
Double Aldol Reaction of Ketone 1v with Aldehyde 2a at –40 ˚C. (Table 14. entry 2).
Following general procedure for Chapter 2, Section 5, silicon tetrachloride (0.23 mL, 2.0 mmol, 4.0 eq) was added dropwise to the solution of benzaldehyde (2a) (0.156 mL, 1.5 mmol, 3.0 equiv), acetylcyclobutane (1v) (0.055 mL, 0.50 mmol, 1.0 equiv), dicyclohexylmethylamine (0.54 mL, 2.5 mmol, 5.0 equiv), and (S)-BINAPO (32.7 mg, 0.050 mmol, 10 mol %) in CH2Cl2 (5.0 mL) at –40
˚C. The crude product was purified by column chromatography (hex/EtOAc = 4:1, SiO210 g) to give double aldol adduct 6b as a regioisomeric mixture (114.8 mg, 77% yield, linear:branched = 4.1:1, 85% ee (linear), 80% ee (branched)).
Double Aldol Reaction of Ketone 1v with Aldehyde 2a at 0 ˚C. (Table 14. entry 3).
Following general procedure for Chapter 2, Section 5, silicon tetrachloride (0.23 mL, 2.0 mmol, 4.0 eq) was added dropwise to the solution of benzaldehyde (2a) (0.156 mL, 1.5 mmol, 3.0 equiv), acetylcyclobutane (1v) (0.055 mL, 0.50 mmol, 1.0 equiv), dicyclohexylmethylamine (0.54 mL, 2.5 mmol, 5.0 equiv), and (S)-BINAPO (32.7 mg, 0.050 mmol, 10 mol %) in CH2Cl2 (5.0 mL) at 0 ˚C.
The crude product was purified by column chromatography (hex/EtOAc = 4:1, SiO210 g) to give double aldol adduct 6b as a regioisomeric mixture (110.2 mg, 71% yield, linear:branched = 8.0:1, 77% ee (linear), 50% ee (branched)).
実験の部 第２章
92 Chapter 2. Section 5.
1H NMR Analysis of the Generation of Chlorosilyl Enol Ether 7 from 5b. (Scheme 54)
To a solution of mono-aldol adduct 5b (37.5 mg, 0.14 mmol), diisopropylethylamine (73 µL, 0.42 mmol, 3.0 equiv.) and (S)-BINAPO (19.2 mg, 0.014 mmol, 10 mol %) in CD2Cl2 (0.75 mL) in a NMR tube capped with a rubber septum was added silicon tetrachloride (40 µL, 0.35 mmol, 2.5 equiv.). Gradual formation of the corresponding (Z)-trichlorosilyl enol ether 7 was observed by 1H NMR analysis.
After 1 h, almost the starting material (>95%) was consumed. The geometry of the enolate was assigned based on a NOESY analysis of the reaction mixture (Chart 1).
(Z)-7
1H NMR (400 MHz, CD2Cl2, internal standard: solvent residual peak = 5.32 ppm):
δ 2.69 (d, 2H, J = 6.0 Hz, Hb and Hc), 3.42 (d, 2H, J = 7.2 Hz, He), 4.86 (t, 1H, J = 7.2 Hz, Hd), 5.33 (t, 1H, J = 6.0 Hz, Ha), 6.98-7.63 (m, 10H).