NJC
0% IPA/hexane, flow rate 1 mL min , l = 254 nm, 20% ee): 34.9, 22.7, 22.6; HRMS (ESI) m/z calcd for C15
Paper
À1
+
2
H
14
O
4
Br (M + H)
À1
t
R
10.35 min (major enantiomer) and 12.85 min (minor enantio- 337.0075, found 337.0075. Compound 10a: IR (neat) cm : 3410,
2
7
1
mer). Compound (+)-7 was obtained as a red solid. [a] + 54.5 3357, 3284, 2920, 2369, 1643, 1402, 1078, 819, 629; H NMR (400
D
À1
(c 0.24, CHCl ); IR (neat) cm : 3448, 3056, 2986, 2924, 2853, MHz, CDCl ): d 8.10 (d, J = 7.2 Hz, 1H), 7.69–7.58 (m, 3H), 5.26
3
3
1
2
685, 2306, 1647, 1426, 1266, 897, 739; H NMR (500 MHz, (t, J = 8.8 Hz, 1H), 4.44 (s, 2H), 3.30–3.27 (m, 2H), 2.16 (s, 3H),
+
CDCl
3
): d 8.04 (d, J = 7.5 Hz, 1H), 7.64–7.62 (m, 2H), 7.58–7.56 1.25 (s, 3H); HRMS (ESI) m/z calcd for C15
14 4
H O Br (M + H)
(m, 1H), 5.16 (dd, J = 8.0, 10 Hz, 1H), 3.80 (d, J = 11 Hz, 1H), 337.0075, found 337.0092.
3
1
.62 (d, J = 11 Hz, 1H), 3.20 (dd, J = 7.5, 15.5 Hz, 1H), 3.12 (dd, J =
0, 15.5 Hz, 1H), 1.27 (s, 3H); C NMR (125 MHz, CDCl ):
3
1
3
Synthesis of 3-bromo-3,4-dihydro-5-hydroxy-2,2-dimethyl-2H-
benzo[h]chromene-6-carbaldehyde 13
d 181.2, 175.5, 170.1, 134.7, 132.2, 130.7, 129.7, 127.4, 124.6,
16.2, 89.1, 73.5, 67.8, 27.1, 19.0; HRMS (ESI) m/z calcd for
1
To a stirred solution of compound 1b (184 mg, 0.65 mmol) in
DCM (4 mL) was added bromine (53 mL, 1.04 mmol) and the
resultant reaction mixture was stirred at room temperature for
+
C H O (M + H) 275.0919, found 275.0928. HPLC analysis of
the compound 7 (Daicel AD-H, 20% IPA/hexane, flow rate 1 mL
min , l = 254 nm, 20% ee): t
1
5
15 5
À1
R
11.29 min (minor enantiomer)
2
h. After completion of the reaction as indicated by TLC, the
and 12.85 min (major enantiomer).
solvent was removed under reduced pressure to give the crude
product, which on column chromatographic purification over
silica gel using 40–45% EtOAc in hexane as an eluent afforded
3-(((2S,3S)-3-(Hydroxymethyl)-3-methyloxiran-2-yl)methyl)-1,4-
dioxo-1,4-dihydronaphthalen-2-yl acetate (+)-8
6
the pure compounds 11a (93% yield) and 11b (5% yield).
Sharpless asymmetric epoxidation of the compound 3b (60 mg,
Compound 11a (75 mg, 0.23 mmol) was treated with 3 N NaOH
at rt for 2 h. After completion of the reaction as indicated by
TLC, the reaction mixture was diluted with DCM and extracted
using DCM (2 Â 5 mL) and water (5 mL). The combined DCM
0
8
.2 mmol) following the above procedure afforded (+)-8 (50 mg,
2
7
0%) as a light yellow oil; [a] + 101.1 (c 0.2, CHCl ); IR (neat)
D
3
À1
cm : 3396, 3298, 2921, 2372, 1745, 1616, 1391, 1225, 1066;
1
3
H NMR (400 MHz, CDCl ): d 8.13–8.08 (m, 2H), 7.77–7.72 (m,
2 4
layers were washed with brine solution and dried over Na SO
2
6
1
H), 3.65 (d, J = 12 Hz, 1H), 3.55 (d, J = 12.4 Hz, 1H), 3.23 (t, J =
and the solvent was removed under reduced pressure to give
the crude product, which on chromatographic purification
over silica gel using 15% EtOAc in hexane as an eluent afforded
Hz, 1H), 2.94 (dd, J = 5.2, 13.6 Hz, 1H), 2.80 (dd, J = 6.8,
1
3
3.6 Hz, 1H), 2.40 (s, 3H), 1.40 (s, 3H); C NMR (100 MHz,
CDCl ): d 184.3, 177.9, 168.0, 152.5, 135.5, 134.4, 134.1, 131.9,
3
the pure compounds 12 (65% yield), 13 (15% yield) and 14
1
1
26.9, 126.8, 65.1, 61.7, 58.0, 23.8, 20.6, 14.4; HRMS (ESI) m/z
(5% yield). Compound 13 was obtained as white crystals. H
+
calcd for C H O (M + H) 317.1025, found 317.1032. HPLC
1
7
17
6
3
(500 MHz, CDCl ) d 14.04 (s, 1H), 10.49 (s, OH), 8.17 (d, J =
analysis of the compound (+)-8 (Daicel AD-H, 20% IPA/hexane,
8
.4 Hz, 1H), 8.11 (d, J = 8.4 Hz, 1H), 7.60 (t, J = 7.2 Hz, IH), 7.42
À1
flow rate 1 mL min , l = 254 nm, 90% ee): t
R
17.54 min (major
(t, J = 7.6 Hz, IH), 4.36 (dd, J = 5.5, 8.0 Hz 1H), 3.50 (dd, J = 8.0,
enantiomer) and 19.82 min (minor enantiomer).
1
7.6 Hz, 1H), 3.26 (dd, J = 8.0, 17.6 Hz, 1H), 1.65 (s, 1H), 1.56 (s,
1
3
1H); C (125 MHz, CDCl ): d 190.8, 165.7, 156.4, 132.7, 129.6,
3
Bromination of compound 3b
123.9, 122.9, 120.4, 118.3, 106.2, 105.2, 79.1, 50.93, 28.4, 26.6,
+
To a stirred solution of compound 3b (30 mg, 0.1 mmol) in dry
DCM (2 mL) at 0 1C was added bromine (6 mL, 2.4 mmol). The
resultant reaction mixture was stirred for 15 min at room
temperature. The reaction mixture was quenched with saturated
22.8; HRMS (ESI) m/z calcd for C H BrO (M + H) 335.0283,
1
6
16
3
found 335.0280.
solution of Na
combined DCM layers were washed with water (5 mL), dried
over anhydrous Na SO and concentrated under reduced pres-
S
2 2
O
3
and extracted with DCM (2 Â 5 mL), the Acknowledgements
Dr Eyong thanks the TWAS-UNESCO Associate Scheme and IIT
Madras for financial support. The authors thank the DST, UGC
and CSIR, New Delhi, for financial support, and the DST-FIST
program for infrastructure facilities at IIT Madras. The authors
also thank Mr V. Ramkumar for single crystal X-ray analysis and
the Government of Cameroon for financial support through the
‘Fonds d’Appuis ‘a la Recherche’.
2
4
sure to give the crude compound. Column chromatographic
purification of the crude compound over silica gel (40–70%
EtOAc in hexane) afforded the bromo derivatives 9a, 9b, 10a and
0b. Compounds 9a and 9b: IR (neat) cm : 3058, 2985, 2874,
741, 1656, 1445, 1375, 1268, 1239, 1097, 1047, 938, 847, 744,
À1
1
1
7
7
1
05; H NMR (400 MHz, CDCl
3
): d 8.19 (dd, J = 0.8, 8.0 Hz, 2H),
.91 (td, J = 0.8, 8.0 Hz, 2H), 7.79 (qd, J = 1.2, 7.6 Hz, 2H), 7.63
(
qd, J = 1.2, 8.0 Hz, 2H), 4.46 (d, J = 8.4 Hz, 1H), 4.36 (dd, J = 1.2,
Notes and references
5
4
1
.6 Hz, 1H), 4.25 (dd, J = 1.2, 6.0 Hz, 1H), 4.20 (d, J = 8.4 Hz, 1H),
.09 (d, J = 8.4 Hz, 1H), 3.93 (d, J = 8.4 Hz, 1H), 3.67 (dd, J = 1.2,
5.6 Hz, 1H), 3.46 (dd, J = 5.6, 18.0 Hz, 1H), 3.24 (dd, J = 6.0, 15.6
1 S. Hooker, J. Am. Chem. Soc., 1936, 58, 1181–1191.
2 (a) K. O. Eyong, K. Krohn, H. Hussain, G. N. Folefoc,
A. E. Nkengfack, B. Schulz and Q. Hu, Chem. Pharm. Bull.,
2005, 53, 616–619; (b) K. O. Eyong, G. N. Folefoc, V. Kuete,
V. P. Beng, K. Krohn, H. Hussain, A. E. Nkengfack, M. Saeftel,
S. R. Sarite and A. Hoerauf, Phytochemistry, 2006, 67, 605–609.
Hz, 1H), 2.91 (dd, J = 1.2, 17.6 Hz, 1H), 1.81 (s, 3H), 1.54 (s, 3H);
1
3
3
C NMR (100 MHz, CDCl ): d 182.3, 180.8, 180.2, 179.1, 138.0,
1
1
37.8, 135.7, 131.3, 131.2 131.1, 130.9, 129.1, 128.8, 125.9, 125.3,
06.8, 84.2, 83.9, 77.5, 75.5, 74.2, 62.9, 58.6, 50.5, 47.9, 37.2,
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New J. Chem.