1602
S. Kotha, R. Ali / Tetrahedron 71 (2015) 1597e1603
4.6. Synthesis of compound 4a
To a solution of compound 3a (1 g, 3.11 mmol) in dry CH2Cl2
(25 mL), was added a solution of PBr3 (0.9 mL, 9.33 mmol) in dry
CH2Cl2 (10 mL) dropwise by using a dropping funnel at 0 ꢁC and the
reaction mixture was stirred at rt for 10 h. At the conclusion of the
reaction (TLC monitoring), the reaction mixture was poured into
ice-cooled water and the organic layer was extracted with CH2Cl2.
The solvent was removed under reduced pressure and the crude
product was purified by silica gel column chromatography (10%
EtOAc-petroleum ether) to afford the compound 4a (1.04 g, 75%) as
a white solid.
Fig. 9. Structures of sulfones 12a and 33a isolated during the DA sequence.
4.1. Preparation of compounds 2a, 2b, 2e, 2f, 2g, 2h and 2i
These compounds have been prepared by the literature pro-
cedures and the 1H, 13C NMR data matched with the literature re-
ported spectral data.14e19
Mp 162e164 ꢁC; Rf¼0.52 (silica gel, 25% EtOAc-petroleum
ether); 1H NMR (400 MHz, CDCl3)
d
¼1.25 (t, J¼7.12 Hz, 6H), 3.57
(s, 4H), 4.20 (q, J1¼7.12 Hz, J2¼14.28 Hz, 4H), 4.63 (s, 4H), 7.20 (s,
2H); 13C NMR (100 MHz, CDCl3)
¼14.17, 30.54, 40.30, 60.42, 62.06,
127.05, 135.60, 141.95, 171.45; IR (neat): ymax¼1446, 1728, 2985,
d
4.2. General procedure for the synthesis of compounds 2c, 2d
and 2j
79
3055 cmꢃ1; HRMS (ESI, Q-ToF) m/z: calculated for C17
H Br2NaO4
20
[MþNa]þ 468.9621, found: 468.9620 and other isotope peaks are
To a suspension of sodium hydride (4 equiv) in dry THF
(w5 mL per mmol), the compounds 1c, 1d or 1j was added and the
reaction mixture was stirred at rt for 15 min. Later, propargyl
bromide (3 equiv) was added and the stirring was continued at
the same temperature for 10e12 h (Table 1). At the conclusion
of the reaction (TLC monitoring), the reaction mixture was
quenched with EtOAc and the solvent was removed under re-
duced pressure. The aqueous layer was extracted with CH2Cl2 and
the crude products were purified by silica gel column chroma-
tography (5% EtOAc-petroleum ether) to deliver the compounds
2c, 2d or 2j.
470.9631 and 472.9695.
4.7. General procedure for the synthesis of 4bej
To a solution of the diols 3bej in CH2Cl2 (w8 mL per mmol), was
added a solution of PBr3 (3 equiv) in CH2Cl2 (w3 mL per mmol)
dropwise by using a dropping funnel at 0 ꢁC. The reaction mixture
was stirred at rt for 12e16 h. At the conclusion of the reaction (TLC
monitoring), the reaction mixture was poured into ice-cooled wa-
ter and the organic layer was extracted with CH2Cl2. The solvent
was removed under reduced pressure and the crude products were
purified by silica gel column chromatography by using appropriate
mixtures of (EtOAc-petroleum ether) to deliver the desired prod-
ucts 4bej.
4.3. Compound 2c
Yellow liquid (83%); Rf¼0.69 (silica gel, 10% EtOAc-petroleum
ether); 1H NMR (400 MHz, CDCl3)
d
¼1.89 (t, J¼2.66 Hz, 2H), 2.53,
4.8. Compound 4b
2.59 (ABq, J¼2.60 Hz, 4H), 3.32 (s, 2H), 7.36e7.40 (m, 1H), 7.48e7.50
(m, 1H), 7.60e7.64 (m, 1H), 7.76 (d, J¼7.57 Hz, 1H); 13C NMR
White solid (49%); Mp 103e105 ꢁC; Rf¼0.48 (silica gel, 25%
EtOAc-petroleum ether); 1H NMR (400 MHz, CDCl3)
d
¼1.04 (s, 6H),
(100 MHz, CDCl3)
d
¼26.10, 37.19, 50.98, 70.90, 79.92, 124.48,126.58,
2.70 (s, 4H), 3.43 (s, 4H), 4.62 (s, 4H), 7.17 (s, 2H); 13C NMR
(100 MHz, CDCl3)
¼28.53, 30.50, 30.79, 38.39, 51.53, 71.31, 127.08,
135.72, 141.38, 202.26; IR (neat): ymax¼1602, 1698, 2928,
127.71, 135.50, 135.71, 153.16, 207.11; IR (neat): ymax¼1608, 1708,
2224, 2840, 2934, 3016, 3310 cmꢃ1; HRMS (ESI, Q-ToF) m/z: cal-
culated for C15H12NaO [MþNa]þ 231.0780, found: 231.0780.
d
79
3019 cmꢃ1; HRMS (ESI, Q-ToF) m/z: calculated for C18
H Br2KO2
20
[MþK]þ 464.9462, found: 464.9457 and other isotope peaks are
4.4. Preparation of compound 3a
466.9440 and 468.9420.
The solution of compound 2a (1.7 g, 7.2 mmol), and 2-butyne-
1,4-diol (1.85 g, 21.60 mmol) in dry ethanol (35 mL) was degassed
with nitrogen for 15 min. Later, Wilkinson’s catalyst (166 mg,
2.5 mol %) and Ti(OiPr)4 (511 mg, 25 mol %) were added and the
reaction mixture was refluxed for 12 h. At the conclusion of the
reaction (TLC monitoring), the solvent was removed under reduced
pressure and the crude product was purified by silica gel column
chromatography (20% EtOAc-petroleum ether) to deliver com-
pound 3a (2.14 g, 68%) as a white solid. The 1H and 13C spectra
matched with the literature reported spectral data.20
4.9. General procedure for the synthesis of sultine derivatives
6aej
To a solution of di-bromo compounds 4aej and TBAB (1 equiv)
in DMF (10 mL), was added rongalite (10 equiv) at 0 ꢁC and the
reaction mixture was stirred at 0 ꢁC for 3 h and at r.t. for another
1e3 h (Table 1). At the conclusion of the reaction (TLC monitoring),
the aqueous layer was extracted with EtOAc and the organic layer
was washed with water (4ꢂ30) to remove the excess amount of
DMF. The solvent was removed under reduced pressure and the
crude products were purified by silica gel column chromatography
(40e50% EtOAc-petroleum ether) to deliver the desired sultine
derivatives 6aej.
4.5. General procedure for the [2D2D2] cycloaddition re-
action of 2bej
The solution of compounds 2bej and 2-butyne-1,4-diol
(3 equiv) in dry ethanol (w5 mL per mmol) was degassed with
nitrogen for 15 min. Later, Wilkinson’s catalyst (2.5 mol %) and
Ti(OiPr)4 (25 mol %) was added and the reaction mixture was
refluxed for 12e24 h (Table 1). At the conclusion of the reaction
(TLC monitoring), the solvent was removed under reduced pressure
and the crude products were directly subjected to the next step
without further purification.
4.10. Compound 6a
White solid (88%); Mp 123e124 ꢁC; Rf¼0.56 (silica gel, 50%
EtOAc-petroleum ether); 1H NMR (400 MHz, CDCl3)
d
¼1.23e1.27
(m, 6H), 3.50 (d, J¼15.25 Hz, 1H), 3.57 (s, 4H), 4.16e4.22 (m, 4H),
4.38 (d, J¼15.24 Hz, 1H), 4.90 (d, J¼13.48 Hz, 1H), 5.23
(d, J¼13.49 Hz, 1H), 7.09 (d, J¼13.48 Hz, 2H); 13C NMR (100 MHz,