The Journal of Organic Chemistry
Note
water (5 mL) and extracted with CH2Cl2 (3 × 10 mL). The combined
organic extracts were washed with brine and dried over MgSO4. The
drying agent was filtered off, and the solvent was evaporated. The
residue was purified by column chromatography (silica, pentane:
EtOAc 10:1) affording 74 mg (0.23 mmol, 66%) of the title compound
5.07 (s, 1H), 4.77 (d, J = 8.4 Hz, 1H), 4.72 (d, J = 10.0 Hz,
1H), 4.47 (d, J = 10.0 Hz, 1H), 4.43 (d, J = 8.4 Hz, 1H), 4.11
(d, J = 17.3 Hz, 1H), 4.03 (d, J = 17.4 Hz, 1H), 3.92 (d, J =
13.9 Hz, 1H), 3.84 (d, J = 12.5 Hz, 1H), 3.69 (d, J = 12.5 Hz,
1H), 3.61 (d, J = 13.9 Hz, 1H) ppm. 13C{1H} NMR
(101 MHz, CDCl3, keto, δ): 212.8, 135.4, 129.2, 128.3, 126.6,
74.1, 71.1, 68.1, 54.9 ppm. HRMS (ESI): [M + H]+ calcd. for
1
28 as a colorless oil. Rf 0.5 (silica, pentane:EtOAc 10:1). H NMR
(400 MHz, CDCl3, δ): 7.25−7.14 (m, 10H), 4.94 (s, 2H), 3.49 (dd,
J = 14.0, 6.7 Hz, 1H), 3.40 (dd, J = 14.0, 6.7 Hz, 1H), 2.46−2.36
(m, 1H), 2.30−1.99 (m, 3H), 1.90−1.79 (m, 1H), 1.74−1.60
(m, 1H) ppm. 13C{1H} NMR (101 MHz, CDCl3, δ): 219.5, 156.5,
137.6, 136.3, 128.8, 128.4, 128.0, 127.9, 127.4, 126.7, 66.6, 58.3, 47.0,
37.7, 32.5, 18.3 ppm. HRMS (ESI): [M + Na]+ calcd. for
+
C11H12NO2 , 190.0863; found, 190.0863 (loss of N2).
IR (film): 2968 (w), 2879 (w), 2105 (s), 1760 (m), 1499 (w),
1448 (w), 1299 (w), 1190 (w), 1067 (w), 967 (w), 930 (w),
764 (w) cm−1.
+
C20H21NNaO3 , 346.1414; found, 346.1420. IR (film): 3440 (w),
2-(Azidomethyl)-2-(4-(trifluoromethyl)phenyl)-1-oxaspiro-
3350 (w), 3029 (w), 2965 (w), 2886 (w), 2250 (w), 1721 (s),
1509 (m), 1456 (w), 1404 (w), 1232 (s), 1137 (w), 1010 (w),
911 (m), 733 (s) cm−1.
[2.3]hexane (7t).
2-(Isothiocyanatomethyl)-2-phenylcyclopentanone (29). Triphe-
nylphosphine (0.11 g, 0.42 mmol, 1.2 equiv) was added at room
temperature to a solution of 6a (75 mg, 0.35 mmol, 1 equiv) and CS2
(0.30 mL, 5.0 mmol, 14 equiv) in THF (0.7 mL, 0.5 m), and the
resulting mixture was stirred for 3 h at room temperature. Thereafter,
the mixture was concentrated, and the residue was purified by column
chromatography (silica, pentane:EtOAc 50:1) affording 58 mg
(0.25 mmol, 72%) of the title compound 29 as a colorless oil. Rf
Compound 7t was prepared according to general method E
using 4t (124 mg, 0.500 mmol, 1.00 equiv), 2 (265 mg,
0.600 mmol, 1.20 equiv), and Cu(dap)2Cl (2.2 mg, 2.5 μmol,
0.50 mol %) in CH3CN (2.5 mL, 0.20 m). The title compound
7t was obtained as a colorless oil (72 mg, 0.33 mmol, 66%). Rf
0.5 (silica, pentane:EtOAc 10:1). 1H NMR (400 MHz, CDCl3,
δ): 7.64 (d, J = 8.2 Hz, 2H), 7.46 (d, J = 8.2 Hz, 2H), 3.89
(d, J = 13.4 Hz, 1H), 3.51 (d, J = 13.4 Hz, 1H), 2.72−2.57
(m, 1H), 2.57−2.44 (m, 1H), 2.42−2.26 (m, 1H), 2.01−1.88
(m, 1H), 1.87−1.68 (m, 2H) ppm. 13C{1H} NMR (101 MHz,
CDCl3, δ): 140.2, 130.1 (q, J = 32.5 Hz), 126.8, 125.4 (q, J =
3.8 Hz), 124.0 (q, J = 272.9 Hz), 69.8, 65.0, 54.1, 29.4, 29.0,
12.7 ppm. 19F NMR (376 MHz, CDCl3, δ): −62.6 (s) ppm.
HRMS (ESI): [M + H]+ calcd. for C13H13F3NO+, 256.0944;
found, 256.0945 (loss of N2). IR (film): 2987 (s), 2972 (s),
2902 (m), 2105 (m), 1408 (m), 1329 (s), 1251 (w),
1
0.3 (silica, pentane:EtOAc 20:1). H NMR (400 MHz, CDCl3, δ):
7.49−7.28 (m, 5H), 3.85 (d, J = 14.2 Hz, 1H), 3.70 (d, J = 14.2 Hz,
1H), 2.84−2.67 (m, 1H), 2.45−2.20 (m, 3H), 2.09−1.98 (m, 1H),
1.88−1.73 (m, 1H) ppm. 13C{1H} NMR (101 MHz, CDCl3, δ):
215.9, 135.4, 131.9, 129.1, 128.1, 126.6, 57.8, 51.6, 37.0, 31.9,
18.3 ppm. HRMS (ESI): [M + H]+ calcd for C13H14NOS+, 232.0791;
found, 232.0801. IR (film): 2972 (s), 2901 (s), 2188 (m), 2084 (s),
1736 (s), 1599 (w), 1497 (w), 1447 (m), 1404 (m), 1339 (m),
1158 (m), 1067 (s), 880 (w), 759 (m) cm−1.
Established Azidation Reactions Performed with tBuABX
(1d) and ABZ (2). 4-Phenylpent-4-enoic Acid (8). Following a
reported procedure,11 a solution of tBuOK (4.91 g, 43.8 mmol,
2.6 equiv) in dry THF (0.5 M) was added under nitrogen to
bromo(methyl)triphenylphosphorane (7.82 g, 21.9 mmol, 1.3 equiv)
in portions at 0 °C. The mixture was stirred at 0 °C for 30 min, and a
solution of 4-oxo-4-phenylbutanoic acid (30) (3.00 g, 16.8 mmol,
1.0 equiv) in dry THF (1 M) was added dropwise. The reaction was
stirred at 0 °C for 1 h and at room temperature overnight. The solvent
was removed in vacuo, and the residue was diluted with DCM and
aqueous NaOH (1 M). The aqueous layer was separated, washed with
DCM, and acidified to pH 1 with concentrated HCl (35%). DCM was
added, and the organic compound was extracted twice with DCM.
The organic layer was washed with water, dried over MgSO4, and
concentrated in vacuo. The crude product was purified by flash
column chromatography (SiO2, DCM/MeOH: 100/0 then 95/5 and
90/10) to give 4-phenylpent-4-enoic acid (8) (2.38 g, 13.5 mmol,
80%). Rf (silica, DCM/MeOH 9/1) 0.70. 1H NMR (400 MHz,
CDCl3, δ): 11.60 (bs, 1 H), 7.46−7.27 (m, 5 H), 5.35 (s, 2 H), 2.87
(t, J = 7.8 Hz, 2 H), 2.56 (dd, J = 8.9, 6.7 Hz, 2 H) ppm. The signals
of the 1H NMR spectra were in accordance with the data reported in
the literature.11
1168 (m), 1127 (m), 1067 (s), 894 (w), 846 (w) cm−1.
Product Functionalization. 2-Phenyl-2-((4-phenyl-1H-1,2,3-tri-
azol-1-yl)methyl)cyclopentanone (27). Triethylamine (0.10 mL,
0.70 mmol, 2 equiv) followed by phenylacetylene (77 μL,
0.70 mmol, 2 equiv) were added to a solution of 6a (75 mg,
0.35 mmol, 1 equiv) and CuI (6 mg, 0.04 mmol, 10 mol %) in THF
(1.7 mL, 0.2 m) at room temperature, and the resulting mixture was
stirred for 16 h at room temperature. Thereafter, the mixture was
concentrated, and the residue was purified by column chromatog-
raphy (silica, pentane:EtOAc 20:1 to 10:1), affording 102 mg
(0.321 mmol, 92%) of the title compound 27 as a colorless oil. Rf 0.3
(silica, pentane:EtOAc 10:1). 1H NMR (400 MHz, CDCl3, δ): 7.61−
7.55 (m, 2H), 7.29−7.10 (m, 9H), 4.60 (d, J = 14.1 Hz, 1H), 4.49
(d, J = 14.1 Hz, 1H), 2.55−2.44 (m, 1H), 2.25−2.13 (m, 1H), 1.99
(dt, J = 19.5, 9.2 Hz, 1H), 1.91−1.82 (m, 1H), 1.72−1.63 (m, 1H),
1.62−1.49 (m, 1H) ppm. 13C{1H} NMR (101 MHz, CDCl3, δ):
217.2, 147.3, 135.7, 130.3, 129.1, 128.6, 128.1, 128.0, 126.6, 125.5,
120.7, 58.6, 56.0, 37.0, 31.4, 17.9 ppm. HRMS (ESI): [M + Na]+
calcd. for C20H19N3NaO+, 340.1420; found, 340.1420. IR (film):
3147 (w), 3066 (w), 2977 (w), 2944 (w), 2888 (w), 2250 (w),
1734 (w), 1464 (w), 1356 (w), 1231 (w), 1158 (w), 1077 (w),
1048 (w), 907 (s), 766 (m), 728 (s) cm−1.
Benzyl ((2-oxo-1-Phenylcyclopentyl)methyl)carbamate (28).
A mixture of 6a (75 mg, 0.35 mmol, 1 equiv) and Pd/C (7 mg,
10%w/w, 10% Pd) in methanol (1.7 mL, 0.2 m) was purged with
hydrogen and then stirred for 16 h under a hydrogen atmosphere.
Thereafter, the mixture was filtered through a plug of Celite and
concentrated. The crude amine was dissolved in CH2Cl2 (0.7 mL, 0.5
m), then NEt3 (0.10 mL, 0.70 mmol, 2 equiv) followed by CbzCl
(75 μL, 0.52 mmol, 1.5 equiv) were added, and stirring was continued
for 3 h at room temperature. Then, the reaction was quenched with
N-Phenyl-N-((2-vinylphenyl)sulfonyl)methacrylamide (10). Fol-
lowing a reported procedure,42 2-bromobenzene-1-sulfonyl chloride
(31) (1.34 g, 5.24 mmol, 1.0 equiv) was dissolved in DMF (52 mL).
The resulting colorless solution was cooled to 0 °C (ice−water bath),
and aniline (32) (1.9 mL, 21 mmol, 4.0 equiv) was added dropwise
via syringe. The cooling bath was removed, and the mixture was
stirred at room temperature for 1.5 h. During this time, it became pale
yellow. The reaction was then quenched by the addition of water
(50 mL). The aqueous layer was extracted with EtOAc (4 × 50 mL). The
organic extracts were washed with aq. HCl (3 × 30 mL) and twice with
brine, dried over MgSO4, filtered, and concentrated under vacuum. The
resulting yellow, crude oil was submitted to flash column chromatography
(SiO2; pentane/EtOAc in pentane 19/1 to 6/4) to provide 2-bromo-N-
phenylbenzenesulfonamide (33) (0.819 g, 2.62 mmol, 50%) as a pale
1
yellow, crystalline solid. Rf (silica, pentane/EtOAc 4/1) 0.39. H NMR
R
J. Org. Chem. XXXX, XXX, XXX−XXX