The Journal of Organic Chemistry
ARTICLE
(s, 1H), 7.09 (dd, J = 8.6, 8.6 Hz, 1H), 7.22 (d, J = 8.6 Hz, 2H), 7.30 (d,
J = 8.6 Hz, 1H), 7.35-7.39 (m, 1H), 7.37 (d, J = 8.6 Hz, 2H), 7.43-7.46
(m, 5H), 7.70 (d, J = 8.6 Hz, 2H), 7.86 (d, J = 8.6 Hz, 2H), 7.93 (d, J = 8.6
Hz, 1H); 1H NMR [500 MHz, (CD3)2SO] δ 2.08-2.17 (m, 1H), 2.31
(s, 3H), 2.43 (s, 3H), 2.86 (dd, J = 14.3, 12.6 Hz, 1H), 3.01-3.16
(m, 3H), 3.44 (dd, J = 11.7, 3.7 Hz, 1H), 3.79-3.86 (m, 1H), 4.37-4.42
(m, 1H), 5.48 (d, J = 5.7 Hz, 1H), 6.56 (s, 1H), 7.17 (dd, J = 8.6, 8.6 Hz,
1H), 7.27-7.33 (m, 3H), 7.34 (d, J = 8.6 Hz, 2H), 7.42 (dd, J = 8.0, 8.0
Hz, 1H), 7.46-7.53 (m, 4H), 7.66 (s, 1H), 7.78 (d, J = 8.0 Hz, 2H), 7.86
(d, J = 8.6 Hz, 2H), 7.89 (d, J = 8.6 Hz, 1H); 13C NMR (125 MHz,
CDCl3) δ 21.6 (2C), 25.7, 34.3, 43.9, 62.2, 63.2, 81.5, 83.0, 84.0, 112.9,
114.3, 117.3, 125.5, 126.8 (3C), 127.1 (2C), 127.5 (2C), 127.9, 128.4,
128.5, 129.2 (2C), 130.0 (4C), 134.8, 135.1, 136.3, 137.5, 144.0, 145.4.
HRMS (FAB) calcd C36H32BrN2O6S2: (M - H)- 731.0891, found
(M - H)- 731.0889.
(2R,5S)-5-[(R)-4-(4-Bromo-1-tosyl-1H-indol-3-yl)buta-1,2-
dienyl]-2-phenyl-3-tosyl-1,3-oxazinane (21a). To a stirred so-
lution of PPh3 (766 mg, 2.92 mmol) in THF (10 mL) was added diethyl
azodicarboxylate (40% solution in toluene, 1.33 mL, 2.92 mmol) at
-15 °C under argon. After stirring for 5 min at this temperature, a solu-
tion of propargylic alcohol 20a (535 mg, 0.729 mmol) in THF (8.0 mL)
was added to the reaction mixture, followed 5 min later by the addition of
a solution of o-nitrobenzenesulfonyl hydrazide (634 mg, 2.92 mmol) in
THF (9.0 mL) at -15 °C. After stirring for 2.5 h at this temperature, the
mixture was allowed to warm to room temperature and stirred for
further 5 h at this temperature. Concentration under reduced pressure
gave an oily residue, which was purified by flash chromatography over
silica gel with n-hexane-EtOAc (4:1) to give 21a as a pale yellow
amorphous solid (404 mg, 77% yield, dr = 94:6): [R]28D -87.0 (c 1.05,
CHCl3); IR (neat) 1964 (CdCdC), 1378 (NSO2), 1343 (NSO2),
1172 (NSO2); 1H NMR (500 MHz, CDCl3) δ 1.94-2.02 (m, 1H), 2.34
(s, 3H), 2.46 (s, 3H), 2.86 (dd, J = 14.9, 12.0 Hz, 1H), 3.25 (dd, J = 11.5,
11.5 Hz, 1H), 3.39-3.44 (m, 1H), 3.49 (ddd, J = 16.2, 6.4, 2.1 Hz, 1H),
3.56 (ddd, J = 16.2, 6.3, 2.1 Hz, 1H), 3.75 (dd, J = 14.9, 4.6 Hz, 1H),
4.55-4.61 (m, 1H), 5.31-5.38 (m, 1H), 6.64 (s, 1H), 7.12 (dd, J = 8.0,
8.0 Hz, 1H), 7.22 (d, J = 8.6 Hz, 2H), 7.30 (s, 1H), 7.32-7.37 (m, 4H),
7.40-7.46 (m, 4H), 7.71 (d, J = 8.6 Hz, 2H), 7.85 (d, J = 8.6 Hz, 2H),
7.94 (d, J = 8.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 21.5, 21.6,
26.2, 31.8, 44.6, 64.2, 83.0, 88.9, 92.0, 112.9, 114.4, 121.4, 125.0, 125.5,
126.8 (2C), 127.1 (2C), 127.5 (2C), 127.7, 128.3, 128.5, 129.0 (2C),
129.9 (2C), 130.0 (2C), 134.9, 135.6, 136.4, 137.8, 143.7, 145.2, 204.4.
HRMS (FAB) calcd C36H32BrN2O5S2: (M - H)- 715.0941, found
(M - H)- 715.0941.
N-[(2S,4R)-6-(4-Bromo-1-tosyl-1H-indol-3-yl)-2-(hydroxy-
methyl)hexa-3,4-dienyl]-4-methylbenzenesulfonamide
(5a). To a stirred mixture of 21a (400 mg, 0.557 mmol, dr = 94:6) in
MeOH/CH2Cl2 (20 mL, 1:1) was added p-toluenesulfonic acid mono-
hydrate (159 mg, 0.836 mmol) at room temperature. After stirring for
3.5 h at 50 °C, concentration under reduced pressure gave an oily
residue. The residue was dissolved in EtOAc, washed with saturated
NaHCO3 and brine, and dried over MgSO4. The filtrate was concen-
trated under reduced pressure to give an oily residue, which was purified
by flash chromatography over silica gel with n-hexane-EtOAc (3:2) to
give 5a as a white amorphous solid (299 mg, 85% yield, dr = 94:6):
[R]28D -50.6 (c 1.15, CHCl3); IR (neat) 3313 (OH), 1963 (CdCdC),
1413 (NSO2), 1372 (NSO2), 1172 (NSO2), 1157 (NSO2); 1H NMR
(500 MHz, CDCl3) δ 1.77 (t, J = 6.3 Hz, 1H), 2.21-2.29 (m, 1H), 2.35
(s, 3H), 2.43 (s, 3H), 2.79-2.90 (m, 2H), 3.39 (ddd, J = 10.3, 6.3, 5.7
Hz, 1H), 3.49 (ddd, J = 10.3, 6.3, 4.5 Hz, 1H), 3.56-3.69 (m, 2H), 4.68
(t, J = 6.6 Hz, 1H), 4.92-4.97 (m, 1H), 5.46-5.52 (m, 1H), 7.09 (dd,
J = 8.0, 8.0 Hz, 1H), 7.23 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.35
(d, J = 8.0 Hz, 1H), 7.42 (s, 1H), 7.71 (d, J = 8.0 Hz, 2H), 7.73 (d, J = 8.0
Hz, 2H), 7.92 (d, J = 8.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 21.5
(2C), 26.2, 40.7, 44.2, 63.4, 90.3, 92.0, 112.8, 114.5, 121.3, 125.2, 125.5,
126.8 (2C), 127.0 (2C), 127.7, 128.6, 129.7 (2C), 130.0 (2C), 134.8,
136.4, 136.9, 143.4, 145.3, 204.7. HRMS (FAB) calcd C29H28BrN2-
O5S2: (M - H)- 627.0628, found (M - H)- 627.0627.
Determination of Relative Configuration of the Allena-
mide 5a: Synthesis of the Authentic Sample rac-5a by
Desilylation of the Known Allenamide rac-24. To a stirred
solution of rac-24a14 (2.6 mg, 0.0033 mmol) in THF (0.30 mL) was
added TBAF (1.00 M solution in THF; 33 μL, 0.033 mmol) at 0 °C. The
mixture was stirred for 30 min at room temperature. Concentration
under reduced pressure gave an oily residue, which was purified by flash
chromatography over silica gel with n-hexane-EtOAc (3:2) to give rac-
5a as a white amorphous solid (1.9 mg, 91% yield).
(S)-1-(4-Bromo-1-tosyl-1H-indol-3-yl)-4-[(2R,5S)-2-phenyl-
3-tosyl-1,3-oxazinan-5-yl]but-3-yn-2-ol (20b). A solution of
(S)-Alpine-Borane (0.5 M in THF, 0.82 mL, 0.137 mmol) was slowly
added to ketone 16 (100 mg, 0.410 mmol) at 0 °C under argon. The
resulting solution was stirred for 33 h at room temperature. After the
mixture was concentrated under reduced pressure, the residue was
diluted with Et2O (3.8 mL). Aminoethanol (0.031 mL, 0.514 mmol)
was slowly added, producing a yellow precipitate that was removed by
filtration through Celite. The filtrate was concentrated under reduced
pressure to give an oily residue, which was purified by flash chromato-
graphy over silica gel with n-hexane-EtOAc (3:1) to give 20b as a pale
yellow amorphous solid (69.5 mg, 69% yield, dr = >95:5): [R]28D -38.2
(c 0.84, CHCl3); IR (neat) 3501 (OH), 1373 (NSO2), 1347 (NSO2),
1170 (NSO2); 1H NMR (500 MHz, CDCl3) δ 1.73 (d, J = 5.2 Hz, 1H),
2.28-2.36 (m, 1H), 2.35 (s, 3H), 2.46 (s, 3H), 3.10 (dd, J = 14.3, 12.0
Hz, 1H), 3.18 (dd, J = 14.6, 6.0 Hz, 1H), 3.25 (dd, J = 14.6, 6.6 Hz, 1H),
3.44 (dd, J = 11.5, 11.5 Hz, 1H), 3.58 (dd, J = 11.5, 4.0 Hz, 1H), 3.95 (dd,
J = 14.3, 2.9 Hz, 1H), 4.54-4.60 (m, 1H), 6.68 (s, 1H), 7.09 (dd, J = 8.0,
8.0 Hz, 1H), 7.21 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.0 Hz, 1H), 7.35-7.41
(m, 3H), 7.43-7.46 (m, 5H), 7.69 (d, J = 8.0 Hz, 2H), 7.87 (d, J = 8.0
Hz, 2H), 7.93 (d, J = 8.0 Hz, 1H); 1H NMR [500 MHz, (CD3)2SO] δ
2.06-2.15 (m, 1H), 2.31 (s, 3H), 2.42 (s, 3H), 2.85 (dd, J = 14.9, 12.0
Hz, 1H), 3.01 (dd, J = 10.9, 7.4 Hz, 1H), 3.11-3.18 (m, 2H), 3.49 (dd,
J = 10.9, 4.0 Hz, 1H), 3.81 (dd, J = 14.9, 4.6 Hz, 1H), 4.36-4.41 (m, 1H),
5.48 (d, J = 5.7 Hz, 1H), 6.57 (s, 1H), 7.18 (dd, J = 8.6, 8.6 Hz, 1H),
7.29-7.35 (m, 5H), 7.41 (dd, J = 8.0, 8.0 Hz, 1H), 7.45-7.53 (m, 4H),
7.68 (s, 1H), 7.78 (d, J = 8.6 Hz, 2H), 7.87 (d, J = 8.6 Hz, 2H), 7.89 (d, J =
8.6 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 21.6 (2C), 25.7, 34.3, 43.9,
62.2, 63.2, 81.4, 83.0, 84.0, 112.9, 114.3, 117.3, 125.4, 126.8 (3C), 127.1
(2C), 127.5 (2C), 127.9, 128.4, 128.5, 129.1 (2C), 130.0 (2C), 130.1
(2C), 134.8, 135.1, 136.2, 137.5, 144.0, 145.4. HRMS (FAB) calcd
C36H32BrN2O6S2: (M - H)- 731.0891, found (M - H)- 731.0891.
(2R,5S)-5-[(S)-4-(4-Bromo-1-tosyl-1H-indol-3-yl)buta-1,2-
dienyl]-2-phenyl-3-tosyl-1,3-oxazinane (21b). By a procedure
identical with that described for synthesis of 21a from 20a, the
propargylic alcohol 20b (135 mg, 0.184 mmol) was converted into
21b as a pale yellow amorphous solid (80.5 mg, 61% yield, dr = 94:6):
28
[R]
þ20.3 (c 0.78, CHCl3); IR (neat) 1964 (CdCdC), 1374
D
(NSO2), 1344 (NSO2), 1172 (NSO2); 1H NMR (500 MHz, CDCl3) δ
1.88-1.96 (m, 1H), 2.30 (s, 3H), 2.46 (s, 3H), 2.87 (dd, J = 14.6,
12.0 Hz, 1H), 3.10 (dd, J = 11.2, 11.2 Hz, 1H), 3.12-3.17 (m, 1H), 3.48
(ddd, J = 16.6, 6.3, 3.0 Hz, 1H), 3.60 (ddd, J = 16.6, 6.9, 2.9 Hz, 1H), 3.75
(dd, J = 14.6, 4.3 Hz, 1H), 4.41-4.46 (m, 1H), 5.32-5.38 (m, 1H), 6.63
(s, 1H), 7.12 (dd, J = 8.6, 8.6 Hz, 1H), 7.20 (d, J = 8.6 Hz, 2H), 7.31-
7.38 (m, 5H), 7.39-7.45 (m, 4H), 7.70 (d, J = 8.6 Hz, 2H), 7.82 (d, J =
8.6 Hz, 2H), 7.95 (d, J = 8.6 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ
21.5, 21.6, 26.1, 32.0, 44.4, 64.3, 83.0, 89.0, 92.2, 112.9, 114.4, 121.3,
125.1, 125.5, 126.8 (2C), 127.1 (2C), 127.5 (2C), 127.8, 128.3, 128.6,
129.0 (2C), 129.9 (4C), 134.9, 135.6, 136.5, 137.8, 143.7, 145.2, 204.6.
HRMS (FAB) calcd C36H32BrN2O5S2: (M - H)- 715.0941, found
(M - H)- 715.0938.
2079
dx.doi.org/10.1021/jo102388e |J. Org. Chem. 2011, 76, 2072–2083