Costa et al.
Su zu k i-Miya u r a Cr oss-Cou p lin g R ea ct ion of o-
Ha loben zyl Su lfon es 1. Syn th esis of Com p ou n d 15. A
solution of benzyl sulfone 1 (0.75 mmol), phenylboronic acid
(142 mg, 1.13 mmol), potassium carbonate (512 mg, 3.75
mmol), palladium acetate (12 mg, 0.038 mmol), and triph-
enylphosphine (20 mg, 0.075 mmol) in DMF (15 mL) was
stirred at 120 °C for 24 h. Ethyl acetate (50 mL) was added
and washed with water (3 × 10 mL), dried (MgSO4), and
evaporated under vacuum. The residue was purified by flash
chromatography affording pure compound 15 (see text) as
colorless prisms; mp: 115-116 °C (AcOEt/n-hexane); IR νmax
141.3, 165.7, and 166.4; MS (EI) m/z 302 (M+, 5%), 201 (49),
172 (49), 155 (52), 129 (100), 128 (73), 127 (36), 57 (99), and
41 (93); HRMS (EI) calcd for C18H22O4: 302.1518. Found:
302.1508.
Syn th esis of p-Br om oben zyl Su lfon e 4. Typ ica l P r o-
ced u r e. To a solution of commercially available p-bromobenzyl
bromide (5.25 g, 21 mmol) in methanol (200 mL) was added
sodium p-toluenesulfinate (16 g, 65 mmol). The suspension was
refluxed for 24 h and solvent evaporated under vacuum. Water
was added (50 mL) and the aqueous phase extracted with ethyl
acetate (3 × 20 mL), affording compound 4 which was
recrystallized in AcOEt/n-hexane as colorless solids (needles)
(5.19 g, 76%). mp 152-153 °C; IR νmax (KBr) 1314, 1282, 1147
cm-1; 1H NMR (300 MHz) δ 2.43 (s, 3H), 4.23 (s, 2H), 6.97 (d,
J ) 8.0 Hz, 2H), 7.27 (d, J ) 7.9 Hz, 2H), 7.40 (d, J ) 7.9 Hz,
2H) and 7.52 (d, J ) 8.0 Hz, 2H); 13C NMR (75 MHz) δ 21.6,
62.2, 123.2, 127.3, 128.6, 129.6, 131.7, 132.5, 134.7, and 145.0;
MS (EI) m/z 326, 324 (M+, 33%), 172 (87), 170 (100), 169 (25),
166 (23), and 165 (27). Anal. Calcd for C14H13BrO2S: C, 51.9;
H, 4.0; S, 9.9. Found: C, 51.3; H, 3.9; S, 10.4.
1
(KBr) 1315, 1290 and 1148 cm-1; H NMR (300 MHz) δ 2.43
(s, 3H), 4.39 (s, 2H), 6.85 (d, J ) 7.3 Hz, 2H), 7.15 (d, J ) 7.3
Hz, 2H), 7.25-7.31 (m, 7H), 7.36-7.39 (m, 1H) and 7.61-7.64
(m, 1H); 13C NMR (75 MHz) δ 21.6, 58.9, 127.2, 127.6, 127.8,
128.1, 128.2, 128.4, 128.5, 128.6, 129.1, 129.6, 130.3, 131.5,
139.8 and 144.4; MS (EI) m/z 322 (M+, 8%), 168 (100), 167
(22), 166 (20), 165 (32), 152 (75), 115 (15) and 91 (22). Anal.
Calcd for C20H18O2S: C, 75.0; H, 5.1; S, 10.0. Found: C, 74.8;
H, 5.0; S, 9.9.
Alk yla tion Rea ction , Ald ol Rea ction , Mich a el Ad d i-
tion Rea ction a n d Ca r boxyla tion Rea ction of Su lfon e 4
Usin g P h osp h a zen e Ba se P 2-Et. All these reactions were
performed as it was described, respectively, for o-halobenzyl
sulfones 1 (see above).
1-(4-Br om op h en yl)-1-(p-tolu en esu lfon yl)eth a n e (18a ):
colorless oil; Rf 0.58 (AcOEt/n-hexane:1/2); IR νmax (neat) 1314,
1285, and 1143 cm-1 (SO2); 1H NMR (300 MHz) δ 1.75 (d, J )
6.8 Hz, 3H), 2.45 (s, 3H), 4.97 (q, J ) 6.8 Hz, 1H), 7.10-7.27
(m, 3H), 7.32-7.43 (m, 2H), 7.51 (d, J ) 8.2 Hz, 2H), and 7.75
(d, J ) 7.3 Hz, 1H); 13C NMR (75 MHz) δ 14.4, 21.6, 63.3, 126.1,
127.7, 128.8, 129.3, 129.9, 130.3, 132.7, 133.9, 134.6, and 144.6;
MS (EI) m/z 340, 338 (M+, 2%), 185 (97), 183 (100), 104 (66),
Son oga sh ir a Cr oss-Cou p lin g Rea ction of Ben zyl Su l-
fon e 1b. Syn th esis of Com p ou n d 16. A suspension of
palladium acetate (4.5 mg, 0.015 mmol), triphenylphosphine
(7.5 mg, 0.029 mmol), sulfone 1b (108 mg, 0.29 mmol), copper
iodide (6 mg, 0.029 mmol), and phenylacetylene (32 µL, 0.29
mmol) in diethylamine (5 mL) was stirred at 60 °C for 24 h.
Solvent was evaporated under vacuum and the residue puri-
fied by flash chromatography giving pure compound 16 (see
text) as colorless needles; mp 113-114 °C (AcOEt/n-hexane).
IR νmax (KBr) 1315, 1285, and 1138 cm-1; 1H NMR (300 MHz)
δ 2.31 (s, 3H), 4.66 (s, 2H), 7.07 (d, J ) 8.5 Hz, 2H), 7.30-
7.52 (m, 1H); 13C NMR (75 MHz) δ 21.5, 60.8, 86.4, 96.5, 122.6,
124.6, 128.1, 128.3, 128.5, 128.7, 129.0, 129.3, 130.1, 131.4,
131.5, 132.1, 135.2, and 144.5; MS (EI) m/z 346 (M+, 100%),
265 (17), 193 (23), 192 (37), 189 (22), 166 (23), 163 (20), 152
(31), and 139 (15). Anal. Calcd for C22H18O2S: C, 76.3; H, 5.2;
S, 9.2. Found: C, 76.4; H, 5.1; S, 9.6.
103 (43), 77 (42), and 51 (22); HRMS (EI) calcd for C15H15
BrO2S: 337.9976. Found: 337.9225.
-
Eth yl (E)-3-(4-br om op h en yl)-2-p r op en oa te (19):42 color-
less oil; Rf 0.75 (AcOEt/n-hexane:1/2); IR νmax (neat) 1633, 1713,
1210 and 1144 cm-1 1H NMR (300 MHz) δ 1.34 (t, J ) 7.3
;
H eck R ea ct ion of o-Iod ob en zyl Su lfon e 1b . Typ ica l
P r oced u r e. A suspension of sulfone 1b (100 mg, 0.27 mmol),
potassium carbonate (75 mg, 0.55 mmol), TBAB (8.5 mg, 0.027
mmol), palladium acetate (4.2 mg, 0.014 mmol), triphenylphos-
phine (8 mg, 0.027 mmol), and the alkene (0.33 mmol) in
acetonitrile (6 mL) was refluxed for 24 h. Solvent was
evaporated under vacuum, and water (10 mL) was added. The
resulting solution was extracted with ethyl acetate (2 × 20
mL), and the combined organic phase was dried (MgSO4) and
evaporated, giving a residue which was purified by flash
chromatography to afford pure compounds 17.
Hz, 3H), 4.27 (q, J ) 7.3 Hz, 2H), 6.42 (d, J ) 16.5 Hz, 1H),
7.37-7.53 (m, 4H), and 7.62 (d, J ) 16.5 Hz, 1H); 13C NMR
(75 MHz) δ 30.8, 60.6, 118.9, 124.5, 129.4, 132.1, 133.4, 143.2,
and 166.7 (CdO); MS (EI) m/z 256, 254 (M+, 5%), 215 (65),
213 (71), 199 (30), 185 (64), 183 (62), 175 (48), 171 (43), 169
(37), 155 (37), 147 (75), 139 (94), 118 (78), 91 (100), 89 (74), 77
(45), and 65 (26); HRMS (EI) calcd for C11H11BrO2: 253.9942.
Found: 253.9923.
Syn th esis of Com p ou n d 20. A solution of benzyl sulfone
4 (244 mg, 0.75 mmol), phenylboronic acid (142 mg, 1.13
mmol), potassium carbonate (512 mg, 3.75 mmol), oxime
carbapalladacycle 21 (4 × 10-3 mmol, 2.5 mg) in DMF (15 mL)
was stirred at 120 °C for 12 h. Ethyl acetate (50 mL) was
added, washed with water (3 × 10 mL), dried (MgSO4), and
evaporated under vacuum. The crude residue was immediately
dissolved in anhydrous THF (5 mL) and treated with HMPA
(1.13 mmol, 210 µL) and BuLi (1.6 M solution in hexanes, 1.13
mmol, 706 µL) at -78 °C. The reaction was stirred at this
temperature for 10 min, and ethyl chloroformate (1.13 mmol,
110 µL) was added. The temperature was allowed to rise slowly
to room temperature, and stirring was continued overnight.
Water (40 mL) and ethyl acetate (50 mL) were added, washed
with water (3 × 10 mL), dried (MgSO4), and evaporated under
vacuum. The resulting residue was chromatographed (flash
silica gel), obtaining 20 (163 mg, 54%) as pale yellow oil; Rf
0.76 (AcOEt/n-hexane): IR νmax (neat) 1725, 1250, 1315, 1290,
and 1148 cm-1; 1H NMR (300 MHz) δ 1.25 (t, J ) 7.3 Hz, 3H),
2.42 (s, 3H), 4.15 (q, J ) 7.3 Hz, 4H), 5.12 (s, 1H), 7.23 (d, J
(E)-2-P h en yl-1-[2-(p-tolu en esu lfon ylm eth yl)p h en yl]-1-
eth en e (17a ): colorless prisms; mp 139-140 °C (AcOEt/n-
1
hexane). IR νmax (KBr) 1320, 1285, and 1139 cm-1; H NMR
(300 MHz) δ 2.41 (s, 3H), 4.49 (s, 2H), 6.65, 6.93 (2d, J ) 15.9
Hz, 2H), and 7.04-7.61 (m, 13H); 13C NMR (75 MHz) δ 20.9,
62.8, 124.5, 126.1, 126.6, 127.6, 127.9, 128.6, 129.1, 129.4,
129.6, 130.7, 131.7, 132.6, 134.9, 136.8, 138.1 and 144.8; MS
(EI) m/z 348 (M+, 100%), 217 (46), 194 (40), 193 (29), 192 (24),
191 (22), 190 (23), 189 (69), 179 (24), 178 (31), and 165 (63).
Anal. Calcd for C22H20O2S: C, 75.8; H, 5.8; S, 9.2. Found: C,
75.5; H, 5.7; S, 9.7.
Syn th esis of 1,2-Disu bstitu ted Ben zen es 3a -c. The
synthesis was accomplished according to the previously de-
scribed cross-coupling reactions followed by the alkylation-
â-elimination step (see above).
Eth yl (E)-3-{2-[(E)-2-(ter t-bu toxyca r bon yl)-1-eth en yl]-
p h en yl}-2-p r op en oa te (3a ): colorless oil; Rf 0.75 (AcOEt/n-
hexane:1/1); IR νmax (neat) 1712, 1633, 1455, 1311, and 1151
) 7.9 Hz, 2H), 7.34-7.44 (m, 5H), and 7.52-7.59 (m, 6H); 13
C
1
cm-1; H NMR (300 MHz) δ 1.35 (t, J ) 6.2 Hz, 3H), 1.60 (s,
NMR (75 MHz) δ 13.9, 21.7, 62.5, 75.1, 126.7, 127.1, 128.8,
129.2, 129.5, 130.0, 130.6, 133.5, 133.8, 140.1, 142.4, 145.3,
and 165.0; MS (EI) m/z 394 (M+, 47%), 241 (60), 240 (45), 211
(41), 168 (32), 167 (86), 165 (79), and 155 (100); HRMS (EI)
calcd for. C23H22O4S: 394.1239. Found: 394.1139.
9H), 4.32 (q, J ) 6.2 Hz, 2H), 6.26, 6.34 (2d, J ) 15.9 Hz, 2H),
7.30-7.48 (m, 2H), 7.56-7.68 (m, 2H), 7.95 and 8.04 (2 × d, J
) 15.9 Hz, 2H); 13C NMR (75 MHz) δ 14.3, 28.2, 60.6, 80.8,
121.8, 123.7, 127.5, 127.5, 127.6, 129.6, 129.7, 129.9, 140.2,
5224 J . Org. Chem., Vol. 67, No. 15, 2002