10
M.A. Omar et al. / Tetrahedron xxx (2014) 1e14
H)¼6.4 Hz, 3J (50-H, 60-H)¼6.4 Hz, 2H, 30-H and 50-H), 7.45 (brdd, 3J
(3-H, 4-H)¼8.3 Hz, 4J (5-F, 3-H)¼3.5 Hz, 1H, 4-H), 7.83 (brdd, 3J (20-
H, 30-H)¼6.4 Hz, 3J (50-H, 60-H)¼6.4 Hz, 2H, 20-H and 60-H); 13C NMR
Et2O¼15:1) gave 3b as a colourless oil in 68% yield (74 mg,
0.34 mmol).
(75 MHz, CDCl3)
d
21.6 (CH3), 70.0 (CH2), 116.5 (d, 4J (CeF)¼3.2 Hz,
4.4.3. Isopropyl 2-methyl-4H-chromene-3-carboxylate
(3c). According to general procedure II, a mixture of CuBr (7 mg,
C-2), 116.8 (d, 2J (CeF)¼24.3 Hz, C-6), 117.2 (d, 2J (CeF)¼22.2 Hz, C-
4), 128.0 (C-20 and C-60), 129.8 (C-30 and C-50), 132.6 (C-10), 134.0 (d,
0.05 mmol), K3PO4 (424 mg,
2
mmol), 2-bromo-1-(4-
3
3J (CeF)¼8.1 Hz, C-3), 135.1 (d, J (CeF)¼8.1 Hz, C-1), 145.1 (C-40),
methylbenzenesulfonatemethyl)benzene (1a) (170 mg, 0.5 mmol)
and isopropyl acetocaetae (2c) (147 mg, 1 mmol) was reacted in dry
CH3CN (2 mL) in a sealed vial at 90 ꢀC for 24 h. Flash chromatog-
raphy over silica gel (cyclohexane/Et2O¼15:1) gave 3c as a colour-
less oil in 70% yield (81 mg, 0.34 mmol): Rf 0.54 (cyclohexane/
~
n
2987, 1687, 1622, 1567, 1455, 1449, 1217, 1097,
161.9 (d, 1J (CeF)¼246.1 Hz, C-5); MS (EI, 70 eV) m/z (%) 357 (1)
[M]þ, 279 (7) [MꢁBr]þ, 203 (6) [MꢁC7H7O2S]þ, 187 (9), 155 (3)
[C7H7O2S]þ, 92 (11); HRMS (EI) Calculated for C14H12BrFO3S
357.9675, found 357.9685.
Et2O¼5:1); IR (ATR)
4.3.5. 2-Bromo-5-chloro-1-(4-methylbenzenesulfonatemethyl)ben-
zene (1e). According to general procedure I, KOH (1.5 g, 27 mmol)
939, 880, 832, 771 cmꢁ1; UV (MeCN) lmax (log ε) 280 (4.12), 232
(3.97) nm; 1H NMR (300 MHz, CDCl3) 1.30 (d, 3J (200-H, 300-H or 400-
d
was added to
a
solution of 2-bromo-5-chlorobenzyl alcohol
H)¼6.3 Hz, 6H, 300-H and 400-H), 2.37 (br s, 3H, 10-H), 3.58 (s, 2H, 4-
H), 5.11 (sept, 3J (200-H, 300-H or 400-H)¼6.3 Hz, 1H, 200-H), 6.90 (dd, 3J
(7-H, 8-H)¼7.9 Hz, 4J (6-H, 8-H)¼1.0 Hz, 1H, 8-H), 7.01 (ddd, 3J (5-H,
6-H)¼7.3 Hz, 3J (6-H, 7-H)¼7.2 Hz, 4J (6-H, 8-H)¼1.0 Hz, 1H, 6-H),
7.09 (br d, 3J (5-H, 6-H)¼7.3, 4J (5-H, 7-H)¼1.5 Hz, 1H, 5H), 7.15
(brddd, 3J (7-H, 8-H)¼7.9 Hz, 3J (6-H, 7-H)¼7.2 Hz, 4J (5-H, 7-H)¼
(598 mg, 2.7 mmol) and p-TsCl (618 g, 2.3 mmol) in Et2O (15 mL).
Flash chromatography over silica gel (petroleum ether/ethyl
acetate¼5:1) gave 1e as a colourless solid in 97% yield (970 mg,
2.6 mmol): mp 108e109 ꢀC; Rf 0.37 (petroleum ether/EtOAc¼6:1);
~
IR (ATR)
n
1348 (C]S), 1187, 1121, 946, 823, 659, 561 cmꢁ1; UV
(MeCN) lmax (log ε) 227 (4.26) nm; 1H NMR (300 MHz, CDCl3)
d
2.44
1.5 Hz, 1H, 7-H); 13C NMR (75 MHz, CDCl3) 19.2 (C-10), 21.9 (C-200),
d
(s, 3H, CH3), 5.08 (s, 2H, CH2), 7.14 (dd, 3J (3-H, 4-H)¼8.3 Hz, 4J (4-H,
6-H)¼2.4 Hz, 1H, 4-H), 7.33 (overlapped, 3H, 6-H, 30-H and 50-H),
7.42 (brd, 3J (3-H, 4-H)¼8.3 Hz, 1H, 3-H), 7.82 (brdd, 3J (20-H, 30-H)¼
6.5 Hz, 3J (50-H, 60-H)¼6.5 Hz, 2H, 20-H and 60-H); 13C NMR (75 MHz,
22.0 (C-400), 24.8 (C-4), 67.4 (C-200), 101.2 (C-3), 115.9 (C-8), 120.6 (C-
4a), 123.9 (C-6), 127.4 (C-7), 128.7 (C-5),150.1 (C-8a), þ160.2 (C-2),
167.1 (C-100); MS (EI, 70 eV) m/z (%) 232 (3) [M] , 189 (46)
[MꢁC3H7]þ, 173 (100) [MꢁOC3H7]þ, 135 (10); HRMS (EI) Calculated
for C14H16O3 232.1099, found 232.1089.
CDCl3)
d
21.6 (CH3), 70.0 (CH2), 120.5 (C-2), 128.0 (C-20 and C-60),
129.7 (C-6), 129.9 (C-30 and C-50), 130.2 (C-4), 132.7 (C-10), 133.7 (C-
5), 133.8 (C-3), 134.7 (C-1), 145.1 (C-40); MS (EI, 70 eV) m/z (%) 375
(13) [M]þ, 295 (64) [MꢁBr]þ, 220 (63) [MꢁC7H7O2S]þ, 204 (90)
[MꢁC7H7O3S]þ, 155 (19) [C7H7O2S]þ, 91 (38); HRMS (EI) Calculated
for C14H12BrClO3S 373.9374, found 373.9353.
4.4.4. tert-Butyl 2-methyl-4H-chromene-3-carboxylate
(3d).5b According to general procedure II, a mixture of CuBr
(7 mg, 0.05 mmol), K3PO4 (424 mg, 2 mmol), 2-bromo-1-(4-
methylbenzenesulfonatemethyl)benzene (1a) (170 mg, 0.5 mmol)
and tert-butyl acetoacetate (2d) (158 mg, 1 mmol) was reacted in
dry CH3CN (2 mL) in a sealed vial at 90 ꢀC for 24 h. Flash chroma-
tography over silica gel (cyclohexane/Et2O¼15:1) gave 3d as a col-
ourless oil in 76% yield (93 mg, 0.38 mmol).
4.4. General procedure II for the Cu(I)-catalyzed synthesis of
4H-chromenes 3aem
An oven-dried 10 mL vial was equipped with a magnetic stir bar
and charged with CuBr (7 mg, 0.05 mmol), K3PO4 (424 mg, 2 mmol),
the 2-bromo-1-(4-methylbenzenesulfonatemethyl)benzene de-
4.4.5. Allyl 2-methyl-4H-chromene-3-carboxylate (3e).5b According
to general procedure II, a mixture of CuBr (7 mg, 0.05 mmol), K3PO4
(424 mg, 2 mmol), 2-bromo-1-(4-methylbenzenesulfonatemethyl)
benzene (1a) (170 mg, 0.5 mmol) and allyl acetoacetate (2e)
(142 mg, 1 mmol) was reacted in dry CH3CN (2 mL) in a sealed vial
at 90 ꢀC for 24 h. Flash chromatography over silica gel (cyclohex-
ane/Et2O¼15:1) gave 3e as a colourless oil in 66% yield (75 mg,
0.32 mmol).
rivative 1 (0.5 mmol) and the b-ketoester 2 (1 mmol) under air. The
vial was sealed, evacuated and backfilled with argon three times,
then dry CH3CN (2 mL) was added. The reaction mixture was stirred
at 90 ꢀC for 24 h. After cooling to room temperature, the reaction
mixture was partitioned between CH2Cl2 (30 mL) and brine
(20 mL). The aqueous phase was extracted with CH2Cl2 (2ꢂ20 mL).
The combined organic layers were dried over anhydrous Na2SO4
and concentrated in vacuo. The residue thus obtained was purified
by flash column chromatography over silica gel to afford the de-
sired product.
4.4.6. Benzyl 2-methyl-4H-chromene-3-carboxylate (3f).5b According
to general procedure II, a mixture of CuBr (7 mg, 0.05 mmol), K3PO4
(424 mg, 2 mmol), 2-bromo-1-(4-methylbenzenesulfonatemethyl)
benzene (1a) (170 mg, 0.5 mmol) and benzyl acetoacetate (2f)
(198 mg, 1 mmol) was reacted in dry CH3CN (2 mL) in a sealed vial at
90 ꢀC for 24 h. Flash chromatography over silica gel (cyclohexane/
Et2O¼15:1) gave 3f as a pale yellow oil in 79% yield (110 mg,
0.39 mmol).
4 . 4 .1. M e t hyl 2 - m e t hyl - 4 H - ch r o m e n e - 3 - c a r b o x yl a t e
(3a).5b According to general procedure II, a mixture of CuBr
(7 mg, 0.05 mmol), K3PO4 (424 mg, 2 mmol), 2-bromo-1-(4-
methylbenzenesulfonatemethyl)benzene (1a) (170 mg, 0.5 mmol)
and methyl acetoacetate (2a) (116 mg, 1 mmol) was reacted in dry
CH3CN (2 mL) in a sealed vial at 90 ꢀC for 24 h. Flash chromatog-
raphy over silica gel (cyclohexane/Et2O¼15:1) gave 3a as a colour-
less solid in 78% yield (79 mg, 0.39 mmol): mp 40e42 ꢀC (lit.5b
40e42 ꢀC).
4.4.7. (2-Methoxyethyl) 2-methyl-4H-chromene-3-carboxylate
(3g). According to general procedure II, a mixture of CuBr (7 mg,
0.05 mmol), K3PO4 (424 mg,
2
mmol), 2-bromo-1-(4-
methylbenzenesulfonatemethyl)benzene (1a) (170 mg, 0.5 mmol)
and 2-methoxyethyl acetoacetate (2g) (165 mg, 1 mmol) was
reacted in dry CH3CN (2 mL) in a sealed vial at 90 ꢀC for 24 h. Flash
chromatography over silica gel (cyclohexane/Et2O¼15:1) gave 3g as
a colourless oil in 66% yield (82 mg, 0.33 mmol): Rf 0.42 (cyclo-
~
4.4.2. Ethyl 2-methyl-4H-chromene-3-carboxylate (3b).5b According
to general procedure II, a mixture of CuBr (7 mg, 0.05 mmol), K3PO4
(424 mg, 2 mmol), 2-bromo-1-(4-methylbenzenesulfonatemethyl)
benzene (1a) (170 mg, 0.5 mmol) and ethyl acetoacetate (2b)
(130 mg,1 mmol) was reacted in dry CH3CN (2 mL) in a sealed vial at
90 ꢀC for 24 h. Flash chromatography over silica gel (cyclohexane/
hexane/Et2O¼5:1); IR (ATR)
n
3267, 2948, 1707, 1624, 1570, 1457,
1377, 1289, 1260, 1054, 877, 763 cmꢁ1; UV (MeCN) lmax (log ε) 329
(3.53), 281 (3.95), 231 (3.96) nm; 1H NMR (300 MHz, CDCl3)
2.38
(s, 3H, 10-H), 3.41 (s, 3H, 400-H), 3.62 (s, 2H, 4-H), 3.65 (t, 3J (200-H, 300-
d