Levoglucosenoneꢀderived chromenes
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 10, October, 2013
2199
J = 1.9 Hz). Found (%): C, 64.28; H, 4.81. C14H12O5. Calculatꢀ
ed (%): C, 64.61; H, 4.65.
In the crystal, molecules 6b are combined between
each other only by weak contacts, among which we can
list the following interactions: Cl..., Cl...H, C—H...O,
C—H...N, and C—H...Br with the shortest distances
3.350(3), 2.83(1), 2.51(1), 2.46(1), and 3.03(1), resꢀ
pectively.
In conclusion, levoglucosenone can serve as a proper
chiral matrix for the synthesis of nonꢀracemic functionalꢀ
ized 2Hꢀchromenes by a domino reaction with 2ꢀhydrꢀ
oxybenzaldehydes and subsequent transformation of the
carbohydrate fragment under the Beckmann fragmentaꢀ
tion conditions.
(2R,5R,5aS)ꢀ2,5ꢀEpoxyꢀ9ꢀnitroꢀ5,5aꢀdihydroꢀ4Hꢀoxepiꢀ
no[4,5ꢀb]chromenꢀ1(2H)ꢀone (3d). The yield was 52%, yellow
25
crystals, m.p. 184—186 C (MeCN), []D +14.4 (c 1.0,
1
DMSO). H NMR, : 3.87 (dd, 1 H, J = 8.0 Hz, J = 5.9 Hz);
4.04 (d, 1 H, J = 8.0 Hz); 5.11 (d, 1 H, J = 2.0 Hz); 5.25 (d, 1 H,
J = 5.8 Hz); 5.43 (s, 1 H); 7.28 (d, 1 H, J = 9.0 Hz); 7.81 (d, 1 H,
J = 2.0 Hz); 8.26 (dd, 1 H, J = 9.0 Hz, J = 2.8 Hz); 8.55 (d, 1 H,
J = 2.8 Hz). 13C NMR, : 66.32, 75.01, 75.52, 98.31, 117.19,
122.01, 122.77, 125.89, 128.08, 133.82, 142.09, 158.37, 188.31.
Found (%): C, 56.65; H, 3.08; N, 5.27. C13H9NO6. Calculatꢀ
ed (%): C, 56.73; H, 3.30; N, 5.09.
(2R,5R,5aS)ꢀ7,9ꢀDichloroꢀ2,5ꢀepoxyꢀ5,5aꢀdihydroꢀ4Hꢀoxꢀ
epino[4,5ꢀb]chromenꢀ1(2H)ꢀone (3e). The yield was 83%, yellow
crystals, m.p. 160—162 C (MeCN). 1H NMR, : 3.86 (dd, 1 H,
J = 7.9 Hz, J = 5.7 Hz); 4.03 (d, 1 H, J = 7.9 Hz); 5.07 (d, 1 H,
J = 2.0 Hz); 5.24 (d, 1 H, J = 5.7 Hz); 5.42 (s, 1 H); 7.66 (d, 1 H,
J = 2.0 Hz); 7.68 (d, 1 H, J = 2.5 Hz); 7.73 (d, 1 H, J = 2.5 Hz).
Found (%): C, 51.93; H, 2.89; Cl 23.95. C13H8Cl2O4. Calculatꢀ
ed (%): C, 52.20; H, 2.70; Cl 23.71.
Experimental
1
H and 13C NMR spectra were recorded on Bruker AMꢀ300
and Bruker DRXꢀ500 spectrometers (300.13 and 500.13 MHz
for H NMR and 125.75 MHz for 13C NMR, respectively) in
DMSOꢀd6. Mass spectra were obtained on a Kratos MSꢀ30 inꢀ
strument (EI, 70 eV). Reaction progress was monitored by TLC
(Silufol, eluent hexane—ethyl acetate (3 : 1)).
Oxepino[4,5ꢀb]chromenꢀ1(2H)ꢀones 3a—e (general proceꢀ
dure). Triethylamine (0.10 g, 1 mmol) was added to a solution of
levoglucosenone 1 (0.63 g, 5 mmol) and the corresponding
2ꢀhydroxybenzaldehyde 2 (5 mmol) in EtOH (3 mL) at ~20 C.
After 5 h (72 h for 3d), a suspension formed was diluted
with water (3 mL), the precipitate was filtered off and dried.
In the case of 3c, an oil formed was extracted with CHCl3
(2×5 mL), the solvent was evaporated, and the residue
was subjected to chromatography on silica gel (eluent hexꢀ
ane—EtOAc (9 : 1)).
1
Reduction of compound 3a with NaBH4. A suspension of 3a
(1 mmol) and NaBH4 (1 mmol) in EtOH (2 mL) was stirred for
1 h at 20 C. The reaction mixture was then diluted with water
(10 mL) and extracted with CHCl3 (3×5 mL). The extract was
dried, the solvent was removed, and the residue was subjected to
chromatography on silica gel (eluent hexane—EtOAc (9 : 1)),
which resulted in the isolation of isomeric alcohols 4 and 4´.
(1R,3R,4S,10aS)ꢀ2,5ꢀEpoxyꢀ2,4,5,5aꢀtetrahydroꢀ1Hꢀoxꢀ
epino[4,5ꢀb]chromenꢀ1ꢀol (4). The yield was 42%, colorless crysꢀ
1
tals, m.p. 104—105 C (MeOH). H NMR, : 3.66 (dd, 1 H,
J = 7.8 Hz, J = 5.8 Hz); 3.79 (dd, 1 H, J = 7.8 Hz, J = 1.3 Hz);
3.99 (dm, 1 H, J = 6.9 Hz); 4.65 (t, 1 H, J = 2.0 Hz); 4.78
(d, 1 H, J = 5.8 Hz); 5.37 (s, 1 H); 5.77 (d, 1 H, J = 6.9 Hz); 6.66
(br.s, 1 H); 6.87 (d, 1 H, J = 7.9 Hz); 6.93 (t, 1 H, J = 7.4 Hz);
7.15 (m, 2 H). Found (%): C, 67.49; H, 5.10. C13H12O4. Calcuꢀ
lated (%): C, 67.23; H, 5.21.
(2R,5R,5aS)ꢀ2,5ꢀEpoxyꢀ5,5aꢀdihydroꢀ4Hꢀoxepino[4,5ꢀb]ꢀ
chromenꢀ1(2H)ꢀone (3a). The yield was 84%, yellow crystals,
24
m.p. 126—127 C (EtOH), []D –206.4 (c 1.0, DMSO).
1H NMR, : 3.84 (dd, 1 H, J = 7.9 Hz, J = 5.8 Hz); 4.00 (d, 1 H,
J = 7.9 Hz); 4.90 (d, 1 H, J = 2.0 Hz); 5.17 (d, 1 H, J = 5.8 Hz);
5.37 (s, 1 H); 7.07 (m, 2 H); 7.41 (t, 1 H, J = 7.9 Hz); 7.53 (d, 1 H,
J = 7.7 Hz); 7.65 (d, 1 H, J = 2.0 Hz). 13C NMR, : 66.33, 74.84,
75.23, 98.41, 115.99, 121.03, 121.90, 122.49, 130.40, 133.14,
135.22, 153.58, 188.65. Found (%): C, 68.05; H, 4.31. C13H10O4.
Calculated (%): C, 67.82; H, 4.38.
(1R,3R,4R,10aS)ꢀ2,5ꢀEpoxyꢀ2,4,5,5aꢀtetrahydroꢀ1Hꢀoxꢀ
epino[4,5ꢀb]chromenꢀ1ꢀol (4´). The yield was 40%, oil. 1H NMR,
: 3.72 (dd, 1 H, J = 7.6 Hz, J = 5.8 Hz); 3.87 (dd, 1 H, J = 7.6 Hz,
J = 1.2 Hz); 4.27 (ddm, 1 H, J = 8.0 Hz, J = 4.8 Hz); 4.69
(t, 1 H, J = 1.9 Hz); 4.77 (d, 1 H, J = 5.8 Hz); 5.14 (d, 1 H,
J = 8.0 Hz); 5.46 (d, 1 H, J = 4.8 Hz); 6.67 (br.s, 1 H); 6.88
(d, 1 H, J = 8.3 Hz); 6.95 (t, 1 H, J = 7.5 Hz); 7.17 (m, 2 H).
Reaction of compound 3a with MeONa. Sodium metal (7 mg,
0.3 mmol) was dissolved in MeOH (2 mL). Compound 3a
(115 mg, 0.5 mmol) was added to this solution, and the reaction
mixture was allowed to stand for 24 h at ~20 C. A precipitate of
compound 3´a (42 mg) was filtered off, the filtrate was conꢀ
centrated and subjected to chromatography on silica gel (eluꢀ
ent hexane—EtOAc (9 : 1)) to additionally isolate 20 mg of
compound 3´a (a total yield 62 mg (57%)) and compound 5a
(35 mg, 27%).
(2R,5R,5aR)ꢀ2,5ꢀEpoxyꢀ5,5aꢀdihydroꢀ4Hꢀoxepino[4,5ꢀb]ꢀ
chromenꢀ1(2H)ꢀone (3´a). Yellow crystals, m.p. 108—109 C
(EtOH). 1H NMR, : 3.94 (dd, 1 H, J = 8.1 Hz, J = 5.3 Hz); 4.33
(d, 1 H, J = 8.1 Hz); 5.24 (t, 1 H, J = 5.2 Hz); 5.31 (dd, 1 H,
J = 5.2 Hz, J = 2.3 Hz); 5.43 (s, 1 H); 6.98 (d, 1 H, J = 8.1 Hz);
7.07 (t, 1 H, J = 7.5 Hz); 7.37 (td, 1 H, J = 7.8 Hz, J = 1.7 Hz);
7.48 (dd, 1 H, J = 7.6 Hz, J = 1.6 Hz); 7.61 (d, 1 H, J = 2.3 Hz).
13C NMR, : 63.47, 70.99, 73.14, 99.31, 116.11, 121.38, 122.72,
(2R,5R,5aS)ꢀ9ꢀBromoꢀ2,5ꢀepoxyꢀ5,5aꢀdihydroꢀ4Hꢀoxꢀ
epino[4,5ꢀb]chromenꢀ1(2H)ꢀone (3b). The yield was 86%, yellow
crystals, m.p. 155—157 C (EtOH), []D –101.3 (c 1.0,
24
1
DMSO). H NMR, : 3.84 (dd, 1 H, J = 7.9 Hz, J = 5.8 Hz);
4.01 (d, 1 H, J = 7.9 Hz); 4.93 (d, 1 H, J = 2.0 Hz); 5.18 (d, 1 H,
J = 5.7 Hz); 5.39 (s, 1 H); 7.03 (d, 1 H, J = 8.7 Hz); 7.56 (dd, 1 H,
J = 8.7 Hz, J = 2.5 Hz); 7.64 (d, 1 H, J = 2.0 Hz); 7.78 (d, 1 H,
J = 2.5 Hz). 13C NMR, : 66.33, 74.95, 75.15, 98.34, 113.71,
118.29, 122.14, 123.94, 132.37, 133.99, 135.28, 152.73, 188.53.
Found (%): C, 50.64; H, 3.11; Br, 25.70. C13H9BrO4. Calculatꢀ
ed (%): C, 50.51; H, 2.93; Br, 25.85.
(2R,5R,5aS)ꢀ2,5ꢀEpoxyꢀ7ꢀmethoxyꢀ5,5aꢀdihydroꢀ4Hꢀoxꢀ
epino[4,5ꢀb]chromenꢀ1(2H)ꢀone (3c). The yield was 91%, yellow
25
1
oil, []D –177.2 (c 1.0, DMSO). H NMR, : 3.82 (s, 3 H);
3.84 (dd, 1 H, J = 7.9 Hz, J = 5.8 Hz); 4.00 (dd, 1 H, J = 7.9 Hz,
J = 1.1 Hz); 4.85 (d, 1 H, J = 1.9 Hz); 5.21 (d, 1 H, J = 5.7 Hz);
5.37 (s, 1 H); 7.02 (t, 1 H, J = 7.9 Hz); 7.11 (dd, 1 H, J = 7.7 Hz,
J = 1.4 Hz); 7.15 (dd, 1 H, J = 8.1 Hz, J = 1.4 Hz); 7.64 (d, 1 H,