888
S. Sato et al.
Paper
Synthesis
13C NMR (75 MHz, CDCl3): δ = 164.7, 162.0 (d, J = 245.5 Hz), 156.2 (q,
J = 36.0 Hz), 136.1, 133.5, 129.3, 129.2, 128.6, 127.1 (d, J = 8.0 Hz),
115.8 (q, J = 288.0 Hz), 115.6 (d, J = 21.5 Hz), 77.2, 63.3, 32.8, 28.0,
23.5, 21.1.
13C NMR (125 MHz, CDCl3): δ = 164.5, 156.4 (q, J = 36.0 Hz), 140.2,
133.4, 129.4, 129.3, 128.6, 127.6, 125.1, 116.0 (q, J = 288.5 Hz), 81.4,
65.8, 34.0, 30.1, 26.8, 22.9, 21.4.
HRMS (ESI): m/z [M + Na]+ calcd for C22H22NO3F3Na: 428.1444; found:
428.1443.
HRMS (ESI): m/z [M + Na]+ calcd for C21H19NO3F4Na: 432.1193; found:
432.1193.
(1R*,2S*)-2-Phenyl-2-(2,2,2-trifluoroacetamido)cycloheptyl Ben-
zoate (trans-9bA)
(1R*,2R*)-2-(2-Methoxyphenyl)-2-(2,2,2-trifluoroacetamido)cy-
clohexyl Benzoate (9aE)
Colorless oil.
Prepared by GPB; triarylaluminum was prepared from 2-methoxy-
phenylmagnesium bromide (1.0 M in THF). After purification, 9aE (59
mg, 70%, cis/trans 10.5:1) was obtained as a yellow oil. Further isola-
tion gave the single diastereomer reported here.
IR (CHCl3): 3427, 1732 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.95 (br s, 1 H), 7.69 (dm, J = 8.0 Hz, 2
H), 7.53 (tm, J = 7.5 Hz, 1 H), 7.36–7.23 (m, 7 H), 5.40 (dd, J = 9.5, 1.5
Hz, 1 H), 3.09 (dd, J = 15.0, 8.5 Hz, 1 H), 2.38 (dd, J = 15.0, 9.5 Hz, 1 H),
2.26–2.17 (m, 1 H), 1.99–1.84 (m, 3 H), 1.78–1.74 (m, 1 H), 1.70–1.51
(m, 3 H); NOE was observed between NH (δ = 7.95) and 1-H (δ = 5.40)
in NOESY spectroscopy.
13C NMR (125 MHz, CDCl3): δ = 167.1, 155.8 (q, J = 36.0 Hz), 138.9,
133.4, 129.6, 129.2, 128.4, 128.3, 127.6, 126.1, 115.7 (q, J = 288.5 Hz),
81.0, 67.5, 33.0, 30.4, 29.2, 26.1, 22.0.
IR (neat): 3429, 1728 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.84 (dm, J = 8.5 Hz, 2 H), 7.54 (tm, J =
7.5 Hz, 1 H), 7.40 (tm, J = 7.5 Hz, 2 H), 7.27–7.19 (m, 2 H), 7.11 (br s, 1
H), 6.93–6.86 (m, 2 H), 6.09 (dd, J = 9.5, 4.5 Hz, 1 H), 3.84 (s, 3 H), 2.88
(dm, J = 14.5 Hz, 1 H), 2.80–2.70 (m, 1 H), 2.00–1.46 (m, 6 H).
13C NMR (75 MHz, CDCl3): δ = 165.5, 156.8, 156.1 (q, J = 35.5 Hz),
133.2, 129.7, 129.4, 129.3, 128.4, 127.8, 126.5, 120.7, 115.9 (q, J =
288.5 Hz), 112.1, 74.4, 64.0, 55.2, 29.6, 27.8, 22.7, 21.4.
HRMS (ESI): m/z [M + Na]+ calcd for C22H22NO3F3Na: 428.1444; found:
428.1444.
HRMS (ESI): m/z [M + Na]+ calcd for C22H22NO4F3Na: 444.1393; found:
444.1392.
(1R*,2R*)-2-Phenyl-2-(2,2,2-trifluoroacetamido)cyclopentyl Ben-
zoate (9cA)
(1R*,2R*)-2-(3,4-Dimethoxyphenyl)-2-(2,2,2-trifluoroacetami-
do)cyclohexyl Benzoate (9aF)
Prepared by GPA; N-(benzoyloxy)enamide 1c (60 mg, 0.20 mmol) was
used as starting material. The residue was purified by PTLC (hexane–
EtOAc, 5:1) to give cis-9cA (31 mg, 41%) as a colorless oil.
Prepared by GPB; triarylaluminum was prepared from 3,4-dime-
thoxyphenylmagnesium bromide (0.50 M in THF). After purification,
9aF (46 mg, 51%) was obtained as a pale yellow oil.
IR (CHCl3): 3429, 1730 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.02 (dm, J = 8.5 Hz, 2 H), 7.63 (tm, J =
7.5 Hz, 1 H), 7.55 (br s, 1 H), 7.50 (tm, J = 7.0 Hz, 2 H), 7.47–7.44 (m, 2
H), 7.36 (tm, J = 7.5 Hz, 2 H), 7.29 (tm, J = 7.5 Hz, 1 H), 5.51 (dd, J = 7.0,
5.5 Hz, 1 H), 2.76 (t, J = 7.5 Hz, 2 H), 2.28–2.22 (m, 1 H), 2.12–2.02 (m,
1 H), 1.97–1.84 (m, 2 H).
13C NMR (125 MHz, CDCl3): δ = 166.1, 156.1 (q, J = 36.0 Hz), 140.1,
133.8, 129.6, 129.3, 128.84, 128.77, 128.1, 125.7, 115.7 (q, J = 288.5
Hz), 82.5, 67.8, 32.9, 28.9, 20.4.
IR (CHCl3): 3426, 1733 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.85 (dm, J = 8.5 Hz, 2 H), 7.57 (tm, J =
7.5 Hz, 1 H), 7.43 (tm, J = 7.5 Hz, 2 H), 6.92 (br s, 1 H), 6.91 (dd, J = 8.5,
2.5 Hz, 1 H), 6.83 (d, J = 2.5 Hz, 1 H), 6.77 (d, J = 8.5 Hz, 1 H), 5.37 (dd,
J = 10.5, 4.5 Hz, 1 H), 3.80 (s, 3 H), 3.70 (s, 3 H), 3.12 (dm, J = 14.5 Hz, 1
H), 2.17–2.08 (m, 1 H), 2.04–1.99 (m, 1 H), 1.95–1.90 (m, 1 H), 1.82–
1.41 (m, 4 H).
13C NMR (75 MHz, CDCl3): δ = 164.6, 156.2 (q, J = 35.5 Hz), 148.7,
148.3, 133.5, 133.0, 129.3, 128.6, 127.6, 115.8 (q, J = 288.5 Hz), 111.0,
118.7, 77.1, 63.4, 55.7, 55.5, 32.9, 28.1, 23.5, 21.2.
HRMS (ESI): m/z [M + Na]+ calcd for C20H18NO3F3Na: 400.1131; found:
400.1130.
HRMS (ESI): m/z [M + Na]+ calcd for C23H24NO5F3Na: 474.1499; found:
474.1502.
(1R*,2R*)-2-Amino-2-phenylcyclohexanol (11aA)
β-Phenyl-β-amino alcohol derivatives cis-9aA (39 mg, 0.10 mmol)
was stirred in 5% NaOH in MeOH solution (2.0 mL) at r.t. The mixture
was stirred at r.t. for 16 h, and then it was concentrated. The residue
was dissolved in CHCl3 (15 mL) and washed with H2O (2 × 10 mL) and
brine (10 mL). The organic layers were dried (MgSO4) and concentrat-
ed in vacuo. The residue was purified by PTLC (hexane–EtOAc, 2:1) to
give β-amino alcohol 11aA (15 mg, 81%) as white crystals; mp 115–
116 °C (hexane–EtOAc).
2-Phenyl-2-(2,2,2-trifluoroacetamido)cycloheptyl Benzoate (9bA)
Prepared by GPA; N-(benzoyloxy)enamide 1b (66 mg, 0.20 mmol)
was used as starting material. The residue was purified by PTLC (hex-
ane–EtOAc, 5:1) to give cis-9bA (27 mg, 33%) and trans-9bA (14 mg,
17%).
IR (KBr): 3187 cm–1
.
(1R*,2R*)-2-Phenyl-2-(2,2,2-trifluoroacetamido)cycloheptyl Ben-
zoate (cis-9bA)
1H NMR (300 MHz, CDCl3): δ = 7.55 (dm, J = 8.5 Hz, 2 H), 7.37 (tm, J =
7.0 Hz, 2 H), 7.28–7.22 (m, 1 H), 3.94 (dd, J = 10.0, 4.0 Hz, 1 H), 1.98 (br
s, 3 H), 1.85–1.71 (m, 4 H), 1.68–1.51 (m, 3 H), 1.48–1.32 (m, 1 H).
White crystals; mp 130–133 °C (hexane–EtOAc).
IR (CHCl3): 3430, 1736 cm–1
.
13C NMR (75 MHz, CDCl3): δ = 146.9, 128.5, 126.7, 125.6, 74.2, 58.2,
38.2, 29.4, 23.8, 21.4.
HRMS (ESI): m/z [M + H]+ calcd for C12H18NO: 192.1383; found:
192.1384.
1H NMR (500 MHz, CDCl3): δ = 7.81 (dm, J = 8.5 Hz, 2 H), 7.55 (tm, J =
7.5 Hz, 1 H), 7.42 (tm, J = 7.5 Hz, 2 H), 7.30 (dm, J = 7.5 Hz, 2 H), 7.25
(tm, J = 7.5 Hz, 2 H), 7.17 (tm, J = 7.0 Hz, 1 H), 7.16 (br s, 1 H), 5.32 (dd,
J = 10.0, 4.5 Hz, 1 H), 2.74–2.69 (m, 1 H), 2.59–2.53 (m, 1 H), 2.03–1.70
(m, 6 H), 1.67–1.58 (m, 2 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, 882–892