D. J. Burnell et al.
FULL PAPER
organic fraction was dried with Na2SO4, the solvent was evapo-
rated, and column chromatography of the residue gave the hetero-
cycle.
0.618 mmol) was dissolved in butanone (3.09 mL). NaI (929 mg,
6.18 mmol) was added, and the mixture was heated under reflux
for 3 h. The solvent was evaporated, and the solid was dissolved in
CH2Cl2 (50 mL). This was washed with equal volumes of water
and saturated aqueous Na2SO3, and finally dried with Na2SO4.
The organic layer was then evaporated to afford crude 27 as a col-
orless oil that was used without further purification. From an ali-
(S)-3-Benzyl-4-tosyl-3,4,6,7-tetrahydrocyclopenta[b][1,4]oxazin-
5(2H)-one (22) via 21: By the one-pot procedure above, 11 (347 mg,
1.00 mmol) and 2 (346 mg, 1.50 mmol) gave, after column
chromatography with 4:1 hexanes/EtOAc, 22 (240 mg, 63%) as a
1
quot: H NMR (500 MHz, CDCl3): δ = 7.66 (d, J = 8.4 Hz, 2 H),
colorless solid; m.p. 173–175 °C. IR (film): ν = 1711, 1642 cm–1.
˜
7.38 (d, J = 8.2 Hz, 2 H), 4.24–4.18 (m, 1 H), 4.03 (dd, J = 11.4,
1.4 Hz, 1 H), 3.36–3.29 (m, 1 H), 3.27–3.21 (m, 1 H), 3.15–3.07 (m,
1 H), 3.00–2.92 (m, 2 H), 2.48–2.44 (m, 5 H), 2.16–2.07 (m, 1 H),
2.01–1.93 (m, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 195.8,
145.6, 142.3, 138.4, 134.4, 130.7, 127.2, 65.9, 55.9, 34.5, 31.8, 25.1,
21.8, 0.5 ppm. HRMS (ESI): 469.9893, [C16H18INO4SNa]+ re-
quires 469.9905. Compound 27 was dissolved in benzene (250 mL),
azobis(isobutyronitrile) (100 mg, 0.618 mmol) was added, and the
mixture was heated under reflux. A solution of nBu3SnH (728 mg,
2.50 mmol) in benzene (50 mL) was added over 48 h after which 27
was not apparent by TLC. An aliquot of the benzene solution was
passed through a small chromatography column (3:1 hexanes/
EtOAc) to provide some 28. 1H NMR (500 MHz, CDCl3): δ = 7.81
(d, J = 8.3 Hz, 2 H), 7.33 (d, J = 8.3 Hz, 2 H), 4.33–4.29 (m, 1 H),
3.99 (broad s, 1 H), 3.85–3.78 (m, 2 H), 2.64–2.56 (m, 1 H), 2.49–
2.41 (m, 4 H), 2.33 (ddd, J = 13.2, 9.2, 1.0 Hz, 1 H), 2.21–2.12
(m, 1 H), 1.84–1.74 (m, 3 H), 1.52–1.44 (m, 1 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 207.2, 144.3, 137.8, 130.0, 127.8, 88.0, 74.2,
69.2, 59.7, 33.4, 30.2, 27.1, 24.5, 21.7 ppm. HRMS (ESI): 344.0921,
[C16H19NO4SNa]+ requires 344.0927. To the benzene solution of
28 was added TsOH (476 mg, 2.5 mmol), and the mixture was
heated under reflux for 24 h. The solution was washed with an
equal volume of water, dried with Na2SO4, and concentrated. Col-
umn chromatography with 2:1 hexanes/EtOAc provided 29
(130 mg, 65% from 19) as a colorless solid; m.p. 171–173 °C. IR
1H NMR (500 MHz, CDCl3): δ = 7.69 (d, J = 8.4 Hz, 2 H), 7.14–
7.06 (m, 5 H), 6.90 (dd, J = 7.8, 1.7 Hz, 2 H), 4.36 (dd, J = 11.3,
1.1 Hz, 1 H), 4.23 (tdd, J = 7.9, 2.9, 1.1 Hz, 1 H), 4.15 (dd, J =
11.0, 2.8 Hz, 1 H), 2.75–2.57 (m, 3 H), 2.51 (d, J = 7.8 Hz, 2 H),
2.45 (ddd, J = 17.0, 6.9, 2.6 Hz, 1 H), 2.38 (s, 3 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 196.8, 172.4, 143.7, 136.6, 136.4, 129.4,
129.3, 128.6, 128.1, 126.7, 115.0, 70.1, 54.2, 36.2, 32.0, 24.4,
21.7 ppm. HRMS (ESI): 406.1075, [C21H21NO4SNa]+ requires
406.1083. In one instance, instead of addition of the H2O, the reac-
tion was quenched with base, and from the resulting solution a
small amount of the intermediate 21 was obtained. 1H NMR
(500 MHz, CD3SOCD3): δ = 7.82 (d, J = 8.2 Hz, 2 H), 7.29 (d, J
= 8.1 Hz, 2 H), 7.22 (dd, J = 7.9, 7.4 Hz, 2 H), 7.15 (dd, J = 8.2,
7.4 Hz, 1 H), 7.01 (d, J = 7.4 Hz, 2 H), 3.85–3.77 (m, 1 H), 3.16
(s, 1 H), 3.03–2.98 (m, 2 H), 2.83 (dd, J = 13.7, 3.4 Hz, 1 H), 2.38–
2.34 (m, 5 H), 2.34–2.29 (m, 2 H), 2.25 (dd, J = 13.2, 10.6 Hz, 1
H) ppm. 13C NMR (125 MHz, CD3SOCD3): δ = 199.6, 195.9,
142.0, 139.0, 139.0, 128.8, 128.7, 128.2, 127.7, 125.9, 108.9, 62.8,
60.4, 37.1, 29.8, 29.3, 20.9 ppm.
2-[(4S)-4-Benzyl-3-tosyloxazolidin-2-yl]-2-hydroxycyclobutanone
(26): 2-Methoxyoxazolidine (11, 350 mg, 1 mmol) and 2 (350 mg,
1.5 mmol) were dissolved in CH2Cl2 (10 mL). The solution was
cooled to –78 °C, after which BF3·OEt2 (0.25 mL, 2 mmol) was
added dropwise. After stirring for 5 min at –78 °C, the mixture was
warmed to –20 °C over 2 h. The mixture was diluted with CH2Cl2
(50 mL), and it was washed with an equal volume of H2O. The
organic layer was dried with Na2SO4, and the solvent was evapo-
rated. THF (10 mL) was added, followed by a 1.0 m solution of
TBAF in THF (2 mL, 2 mmol), and the mixture was stirred at
room temp. for 1 h. The solvent was evaporated, and CH2Cl2
(50 mL) was added. After washing with saturated aqueous NH4Cl,
the organic layer was dried with Na2SO4 and the solvent was evap-
orated. Column chromatography with 2:1 hexanes/EtOAc, afforded
26 (201 mg, 50%), a mixture of diastereomers, as a colorless oil.
(film): ν = 1707, 1645 cm–1. 1H NMR (500 MHz, CDCl ): δ = 7.77
˜
3
(d, J = 8.3 Hz, 2 H), 7.31 (d, J = 8.5 Hz, 2 H), 5.18 (d, J = 8.2 Hz,
1 H), 3.85–3.79 (m, 1 H), 3.78–3.71 (m, 1 H), 3.71–3.67 (m, 1 H),
2.65–2.55 (m, 1 H), 2.47–2.42 (m, 5 H), 2.42–2.34 (m, 3 H), 2.10–
2.01 (m, 1 H), 1.86–1.78 (m, 1 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 202.0, 154.3, 153.4, 143.9, 137.6, 130.0, 127.0, 74.6,
53.3, 32.8, 31.4, 27.3, 26.4, 21.7 ppm. HRMS (ESI): 344.0925,
[C16H19NO4SNa]+ requires 344.0927.
N-((2S)-1-{[(cis)-3-Hydroxy-1-oxo-3a,4,5,6,7,7a-hexahydro-1H-
inden-2-yl]oxy}-3-phenylpropan-2-yl) Tosylate (31): A solution of 11
(347 mg, 1.00 mmol) in CH2Cl2 (10 mL) was cooled to –78 °C, and
a solution of 30 (426 mg, 1.50 mmol) in CH2Cl2 (9 mL) was added.
BF3·Et2O (0.25 mL, 2.0 mmol) was added slowly, the solution was
stirred at –78 °C for 15 min, and then the solution was warmed to
–20 °C. After 2 h, the solution was re-cooled to –78 °C, and H2O
(0.18 mL, 10 mmol) and BF3·Et2O (1.8 mL, 15 mmol) were added
over 15 min. The solution was warmed to room temp. overnight
and it was diluted with CH2Cl2 (50 mL). The solution was ex-
tracted with 1 m aqueous NaOH (50 mL). Acidification of the
aqueous layer with 12 m HCl was followed by the re-extraction of
the product into CH2Cl2 (3ϫ 50 mL). The combined organic ex-
tracts were dried with Na2SO4, and then evaporated to give 31
IR (film): ν = 1790 cm–1 1H NMR (500 MHz, CDCl3) for the
.
˜
major isomer: δ = 7.79 (d, J = 8.4 Hz, 2 H), 7.38 (d, J = 8.0 Hz, 2
H), 7.34–7.20 (m, 3 H), 7.17 (d, J = 7.6 Hz, 2 H), 5.12 (s, 1 H),
3.93 (s, 1 H), 3.87 (dd, J = 9.0, 5.2 Hz, 1 H), 3.84–3.78 (m, 1 H),
3.34–3.24 (m, 2 H), 3.18–3.06 (m, 1 H), 3.01–2.85 (m, 1 H), 2.80–
2.68 (m, 2 H), 2.44 (s, 3 H), 2.17–2.07 (m, 1 H) ppm. 13C NMR
(125 MHz, CDCl3) for the major isomer: δ = 208.2, 145.3, 137.0,
132.6, 130.4, 129.2, 129.0, 128.4, 127.1, 92.8, 92.7, 70.2, 61.9, 42.6,
40.6, 23.4, 21.8 ppm. 1H NMR (500 MHz, CDCl3) for the minor
isomer: δ = 7.79 (d, J = 8.4 Hz, 2 H), 7.38 (d, J = 8.0 Hz, 2 H),
7.34–7.20 (m, 3 H), 7.12 (d, J = 7.8 Hz, 2 H), 5.15 (s, 1 H), 4.38
(s, 1 H), 3.96–3.91 (m, 1 H), 3.70 (dd, J = 9.0, 3.7 Hz, 1 H), 3.26
(dd, J = 8.9, 6.4 Hz, 1 H), 3.18–3.06 (m, 1 H), 3.01–2.85 (m, 2 H),
2.80–2.68 (m, 1 H), 2.63–2.56 (m, 1 H), 2.43 (s, 3 H), 2.17–2.07 (m,
1 H) ppm. 13C NMR (125 MHz, CDCl3) for the minor isomer: δ
= 208.6, 145.3, 137.3, 133.0, 130.4, 129.3, 128.9, 128.3, 126.9, 92.8,
92.3, 70.4, 62.2, 42.1, 40.7, 25.0, 21.8 ppm. HRMS (ESI): 424.1182,
[C21H23NO5SNa]+ requires 424.1189.
1
(250 mg, 55%) as a yellow oil. H NMR (500 MHz, CDCl3): δ =
7.59 (d, J = 8.2 Hz, 2 H), 7.21–7.15 (m, 5 H), 7.05 (d, J = 7.9 Hz,
2 H), 6.08 (d, J = 8.0 Hz, 1 H), 4.00 (dd, J = 10.6, 5.7 Hz, 1 H),
3.87 (dd, J = 10.5, 3.1 Hz, 1 H), 3.67–3.59 (m, 1 H), 2.83 (dd, J =
13.9, 7.6 Hz, 1 H), 2.73 (dd, J = 13.8, 6.9 Hz, 1 H), 2.38 (s, 3 H),
1.89–1.74 (m, 3 H), 1.68–1.50 (m, 3 H), 1.41–1.18 (m, 2 H) ppm.
(S)-4-Methyl-N-(8-oxo-3,4,5,6,7,8-hexahydro-2H-cyclopenta[b]ox- 13C NMR (125 MHz, CDCl3) (slow exchange): δ = 143.5, 137.3,
epin-3-yl) Tosylate (29) via 27 and 28: Compound 19 (220 mg, 137.1, 133.7, 129.8, 129.7, 129.5, 128.7, 128.7, 127.1, 126.7, 72.2,
1330
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Eur. J. Org. Chem. 2015, 1325–1332