Brinton Seashore-Ludlow et al.
UPDATES
brine, dried over MgSO4, filtered and concentrated at re-
duced pressure. The residue was purified by silica gel chro-
matography (hexanes/EtOAc 4:1 to 3:1) to afford 19; yield:
(E)-Isopropyl 2-(N,2-Dimethyl-3-phenylpent-2-
enamido)benzoate (17)
1
Prepared from 13 as described for 8 except using i-PrOH
(dried over 4 ꢃ MS) instead of methanol to afford 17 as a
white solid that was purified by silica gel chromatography
(hexanes/EtOAc 4:1); yield: 9 mg (32%); mp 99.5–
100.28C.1H NMR (500 MHz, CDCl3): d (major isomer)=
7.93 (dd, J=7.8, 1.5 Hz, 1H), 7.54–7.07 (m, 6H), 6.69–6.65
(m, 2H), 5.16 (m, 1H), 3.27 (s, 3H), 2.42–2.35 (m, 1H),
2.31–2.22 (m, 1H), 1.30–1.27 (m, 6H), 1.25 (s, 3H), 0.74 (t,
J=7.4 Hz, 3H); d (minor isomer)=7.85 (dd, J=7.8, 1.4 Hz,
1H), 7.54–7.07 (m, 8H), 5.13–5.07 (m, 1H), 3.38 (s, 3H),
2.48–2.42 (m, 2H), 1.76 (s, 3H), 1.31–1.27 (m, 6H), 0.86 (t,
J=7.5 Hz, 1H); 13C NMR (126 MHz, CDCl3): d (mixture of
isomers)=172.6, 171.9, 165.2, 165.0, 143.0, 142.5, 142.0,
140.2, 140.1, 132.8, 132.5, 131.8, 130.7, 129.9, 129.9, 129.2,
128.6, 128.5, 128.3, 128.2, 128.1, 128.0, 128.0, 127.4, 126.8,
126.5, 69.3, 68.4, 39.2, 37.3, 29.2, 28.6, 21.8, 21.8, 17.2, 16.3,
12.5, 12.4; IR (neat): nmax =2977, 2935, 1720, 1643, 1489,
9 mg (24%). H NMR (500 MHz, CDCl3): d=7.81 (dd, J=
7.7, 1.5 Hz, 1H), 7.63 (d, J=7.6 Hz, 1H), 7.58 (td, J=7.8,
1.6 Hz, 1H), 7.48–7.43 (m, 1H), 7.39–7.32 (m, 2H), 7.30–
7.25 (m, 1H), 7.23–7.15 (m, 4H), 7.02–6.97 (m, 2H), 5.06 (d,
J=13.0 Hz, 1H), 4.98 (d, J=13.0 Hz, 1H), 3.21 (s, 3H), 1.35
(s, 3H); 13C NMR (126 MHz, CDCl3): d=170.04, 166.35,
142.88, 141.97, 138.84, 138.46, 133.84, 133.22, 132.11, 130.81,
130.44, 129.34, 129.11, 128.26, 127.80, 127.56, 127.50, 127.49,
127.11, 126.86, 67.65, 37.64, 17.80; IR (neat): nmax =1736,
1647, 1493, 1446, 1358, 1292, 1122, 702 cmꢀ1; HR-MS
(FAB+); m/z=384.1595, calcd. for C25H21NO3 (M+H):
384.1594.
(Z)-1’,4-Dimethyl-5-phenyl-1H-spiro
ACHTUNGTREN[NUNG benzo[c]oxe-
pine-3,2’-benzo[d][1,3]oxazin]-4’(1’H)-one (20)
A
ACHTUNGTRENNUNG
Prepared from 18 in the reaction that also yielded 19, af-
fording 20; yield: 13 mg (35%). 1H NMR (500 MHz,
CDCl3): d=8.04 (d, J=7.7 Hz, 1H), 7.54–7.34 (m, 5H),
7.22–7.11 (m, 4H), 6.94 (t, J=7.5 Hz, 1H), 6.84 (d, J=
7.8 Hz, 1H), 6.80 (d, J=8.4 Hz, 1H), 5.35 (d, J=13.2 Hz,
1H), 4.43 (d, J=13.2 Hz, 1H), 2.92 (s, 3H), 1.86 (s, 3H);
13C NMR (126 MHz, CDCl3): d=162.06, 147.53, 143.48,
142.67, 139.09, 137.13, 135.88, 133.39, 131.68, 130.23, 128.94,
128.78, 127.64, 127.51, 127.12, 126.79, 119.14, 114.89, 112.84,
111.87, 65.54, 31.92, 20.77; IR (neat): nmax =1728, 1608, 1489,
1350, 1130, 1076, 945, 729 cmꢀ1; HR-MS (FAB+): m/z=
384.1582, calcd. for C25H21NO3 (M+H): 384.1594.
1450, 1369, 1284, 1107, 1072, 771, 706 cmꢀ1
; HR-MS
(FAB+): m/z=366.2061, calcd. for C23H27NO3 (M+H):
366.2064.
(Z)-3-[2-(Hydroxymethyl)phenyl]-N-(2-iodophenyl)-
N,2-dimethyl-3-phenylprop-2-enamide (18)
First the amide 37 (35 mg, 0.06 mmol) was methylated as de-
scribed for 13 to afford to afford methylated 37a as a colour-
less oil that was purified by silica gel chromatography hexa-
nes:EtOAc (10:1); yield: 35 mg (98%).
To a solution of methylated 37a (35 mg, 0.058 mmol) in
THF (0.5 mL) at 08C was added tetrabutylammonium fluo-
ride (37 mg, 0.117 mmol) and the resultant mixture stirred
for 5 min. It was then warmed to room tempertaure and
stirred overnight. The solvent was removed at reduced pres-
sure and the residue purified using silica gel chromatogra-
phy (hexane/EtOAc 4:1 to 3:1) to afford 18 as a white solid;
yield: 26.5 mg (95%); mp 157.5–158.38C. 1H NMR
(500 MHz, CDCl3): d (major rotamer)=7.68 (d, J=7.8 Hz,
1H), 7.43–7.00 (m, 11H), 6.82 (t, J=7.6 Hz, 1H), 6.08 (br s,
1H), 4.23 (br s, 2H), 3.21 (s, 3H), 2.19 (s, 3H); d (minor
rotamer)=7.82 (d, J=6.9 Hz, 1H), 7.47–6.93 (m, 11H), 6.73
(d, J=7.3 Hz, 1H), 4.60 (s, 2H), 2.97 (s, 3H); 13C NMR
(126 MHz, CDCl3): d (mixture of rotamers)=172.84, 172.29,
145.36, 144.32, 140.38, 139.78, 139.16, 138.78, 132.20, 131.22,
130.05, 129.70, 129.20, 128.63, 128.53, 128.45, 128.36, 128.05,
127.85, 127.53, 127.49, 127.36, 98.64, 97.57, 63.39, 63.02,
38.91, 37.31, 17.10; IR (neat): nmax =3383, 1624, 1481, 1439,
(E)-N-(2-Iodophenyl)-4-methyl-N-(2-methylpent-2-
en-1-yl)benzenesulfonamide (25a)
To a solution of NaH (60% in mineral oil, 9 mg, 0.22 mmol,
1.2 equiv.) in 300 mL DMF was added N-(2-iodophenyl)-4-
methylbenzenesulfonamide[27] (70 mg, 0.19 mmol, 1.0 equiv.)
via cannula (0.5 mL, 0.5 mL rinse, DMF). The mixture was
stirred for 35–40 min and then (E)-1-bromo-2-methylpent-2-
ene[28] (45 mg, 0.28 mmol, 1.5 equiv.) was added via cannula
(0.5 mL, 0.5 mL rinse, DMF). The reaction was stirred over-
night and then poured into water. The aqueous phase was
extracted 3 times with EtOAc, dried over MgSO4, filtered
and concentrated. The crude residue was subjected to
column chromatography 210: 40 hexanes:EtOAc to give the
desired product 25a; yield: 83 mg (0.18 mmol, 97%).
1H NMR (500 MHz, CDCl3): d=7.86 (dd, J=7.9, 1.4 Hz,
1H), 7.62 (d, J=8.3 Hz, 2H), 7.30 ꢀ7.22 (m, 3H), 6.97 (td,
J=7.7, 1.5 Hz, 1H), 6.89 (dd, J=7.9, 1.5 Hz, 1H), 4.92 (t,
J=7.2 Hz, 1H), 4.19 (d, J=13.3 Hz, 1H), 3.89 (d, J=
13.3 Hz, 1H), 2.43 (s, 3H), 1.82 (p, J=7.4 Hz, 2H), 1.71 (s,
3H), 0.69 (t, J=7.5 Hz, 3H); 13C NMR (126 MHz, CDCl3):
d=143.7, 141.5, 140.6, 136.6, 134.1, 131.0, 129.6, 129.6, 128.6,
128.5, 128.4, 102.6, 59.8, 21.7, 21.2, 15.5, 13.6; IR (neat):
1389, 1080, 1018, 764 cmꢀ1
484.0767, calcd. for C24H22INO2 (M+H): 484.0768.
; HR-MS (FAB+): m/z=
(Z)-5,7-Dimethyl-8-phenyldibenzo
ACHUTGTNRENN[GU c,i]ACHUTNGTREN[NUNG 1,5]oxaaza-
cycloundecene-6,15(5H,13H)-dione (19)
AHCTUNGTRENNUNG
nmax =2962, 2929 2871, 1596, 1465, 1349 cmꢀ1
; HR-MS
A
round-bottom flask was charged with 18 (46.2 mg,
0.096 mmol), Pd2dba3·CHCl3 (5.2 mg, 0.005 mmol), (2-
PACHTUNGTRENNUNG
(FAB+): m/z=456.0477, calcd. for C19H22INO2S (M+H):
furyl)3 (6.7 mg, 0.03 mmol), DABCO (46.7 mg 0.38 mmmol),
DMAP (4.7 mg, 0.038 mmol) and DMA (1 mL). The solu-
tion was frozen in a dry-ice/acetone bath, the flask was evac-
uated and filled with CO two times. The mixture was then
heated to 808C and stirred for 4 h, then cooled to room tem-
perature and diluted with EtOAc. This mixture washed with
456.0489.
212
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 205 – 216