H
Synthesis
A. Benmaati et al.
Paper
1
10-(Furan-2-yl)-7-(furan-2-ylmethyl)-8-hydroxy-7-aza-
H NMR (300 MHz, CDCl ): δ = 7.41–7.26 (m, 8 H), 7.25–7.03 (m, 5 H),
3
spiro[4.5]decane-1,6-dione (3ec)
6.31 (d, J = 1.8 Hz, 1 H), 6.29 (d, J = 1.9 Hz, 1 H), 6.28 (d, J = 3.4 Hz, 1 H),
.25 (d, J = 3.2 Hz, 1 H), 4.80 (d, J = 15.5 Hz, 1 H), 4.67 (s, 1 H), 4.63 (d,
J = 2.8 Hz, 1 H), 4.58 (d, J = 3.8 Hz, 2 H), 4.31 (d, J = 15.9 Hz, 1 H), 4.16
dd, J = 13.9, 2.2 Hz, 1 H), 3.71 (s, 1 H), 3.67 (s, 3 H), 3.47–3.24 (m, 1
H), 2.91 (dd, J = 13.9, 6.7 Hz, 1 H), 2.75 (t, J = 13.6 Hz, 2 H), 2.45–2.07
6
Following the general procedure, the reaction of N-(furan-2-ylmeth-
yl)-2-oxocyclopentanecarboxamide (264 mg, 0.89 mmol) with furyl-
acrolein (2c; 70 mL, 0.979 mmol) in the presence of PS-BEMP (40.6
mg, 10 mol%) in THF (1.8 mL) at r.t. for 24 h afforded the product 3ec
as a white solid (310 mg, 98%). The crude product was obtained with
(
(m, 8 H), 2.04–1.67 (m, 4 H), 1.11–0.95 (m, 2 H).
13
6
:4:1:1 dr; R = 0.18 (Et O/PE, 7:3). Data given are for the mixture of
C NMR (75 MHz, CDCl ): δ (major) = 217.1 (C), 172.7 (C), 172.3 (C),
f
2
3
four diastereomers.
150.5 (C), 141.8 (CH), 138.1 (C), 128.8 (CH), 128.5 (2 CH), 127.4 (2
CH), 110.5 (CH), 108.8 (CH), 84.8 (COH), 61.4 (C), 54.1 (CH ),40.23
1
H NMR (300 MHz, CDCl ): δ = 7.28 (s, 1 H), 7.26 (dd, J = 1.6, 0.8 Hz, 3
3
3
(
CH), 39.8 (CH ), 38.0 (CH ), 36.1 (CH ), 30.1 (CH ), 19.5 (CH ); δ (mi-
H), 7.24 (dd, J = 1.9, 0.6 Hz, 1 H), 7.23 (d, J = 1.3 Hz, 1 H), 7.22–7.20 (m,
2 2 2 2 2
nor) = 217.6 (C), 172.1 (C), 170.2 (C), 150.8 (C), 141.7 (CH), 138.6 (C),
28.6 (2 CH), 128.2 (CH), 127.9 (2 CH), 110.4 (CH), 109.0 (CH), 84.9
COH), 59.9 (C), 53.8 (CH ), 49.9 (CH), 40.2 (CH ), 38.1 (CH ), 37.0
2 H), 6.26–6.22 (m, 8 H), 6.22–6.19 (m, 4 H), 6.02 (d, J = 3.3 Hz, 1 H),
6.00 (d, J = 3.3 Hz, 1 H), 5.97 (d, J = 3.2 Hz, 2 H), 5.16–5.10 (m, 1 H),
5.09–5.02 (m, 2 H), 4.95 (d, J = 15.5 Hz, 4 H), 4.90 (d, J = 2.8 Hz, 1 H),
4.84 (d, J = 6.1 Hz, 3 H), 4.81 (d, J = 4.8 Hz, 1 H), 4.45–4.37 (m, 1 H),
4.33 (d, J = 15.8 Hz, 1 H), 4.19 (d, J = 15.5 Hz, 2 H), 4.08 (d, J = 7.2 Hz, 1
1
(
(
3
2
2
CH ), 33.6 (CH ), 20.0 (CH ).
2
2
2
HRMS (ESI+): m/z [M + H]+ calcd for C22H20NO : 398.1598; found:
6
H), 4.05 (d, J = 2.6 Hz, 1 H), 4.04–4.01 (m, 1 H), 3.67 (dd, J = 13.7, 2.7
Hz, 1 H), 3.50 (dd, J = 13.5, 2.4 Hz, 1 H), 3.06 (dd, J = 13.9, 4.4 Hz, 1 H),
398.1597.
2
1
.94 (dd, J = 13.8, 3.4 Hz, 1 H), 2.85 (d, J = 13.1 Hz, 1 H), 2.79–2.70 (m,
H), 2.49–2.38 (m, 3 H), 2.23–2.03 (m, 14 H), 1.98–1.81 (m, 10 H).
Methyl 8-Hydroxy-1,6-dioxo-7,10-diphenyl-7-azaspiro[4.5]dec-
ane-8-carboxylate (3fd)
13
C NMR (75 MHz, CDCl ): δ (major 1) = 218.4 (C), 171.3 (C), 153.2 (C),
3
Following the general procedure, the reaction of 2-oxo-N-phenylcy-
clopentanecarboxamide (500 mg, 2.46 mmol) with methyl (E)-2-oxo-
4-phenylbut-3-enoate (2d; 514 mg, 2.70 mmol) in the presence of PS-
BEMP (112.5 mg, 10 mol%) in THF (5 mL) at r.t. for 32 h afforded the
product 3fd as a white solid (96.5 mg, 98%). The crude product was
obtained with 6:2:2:1 dr. Two diastereomers were separated.
1
5
1
1
5
50.2 (C), 142.2 (2 CH), 110.3 (2 CH), 108.6 (CH), 106.9 (CH), 77.3 (C),
9.8 (C), 40.1 (CH ), 39.4 (CH ), 39.3 (CH ), 32.9 (CH), 31.5 (CH ),
2
2
2
2
9.30 (CH ); δ (major 2) = 216.8 (C), 170.1 (C), 153.6 (C), 150.4 (C),
2
42.0 (2 CH), 141.6 (CH), 141.3 (CH), 110.4 (CH), 107.8 (CH), 78.3 (C),
8.8 (C), 41.9 (CH ), 36.5 (CH), 34.1 (CH ), 31.7 (CH ), 30.9 (CH ), 19.7
2
2
2
2
(CH ); δ (minor 1 + minor 2) = 218.2 (C), 217.5 (C), 171.5 (C), 171.4
2
First fraction: one diastereomer was isolated as a yellow oil (155 mg,
(C), 152.6 (C), 152.5 (C), 150.5 (C), 150.4 (C), 142.1 (CH), 141.8 (CH),
1
6%); R = 0.75 (Et O/PE, 1:1).
f
2
141.7 (CH), 110.6 (CH),110.5 (CH), 108.5 (CH), 108.1 (CH), 107.4 (CH),
107.3 (CH), 107.28 (CH), 107.20 (CH), 110.2 (CH), 78.6 (C), 78.3 (C),
60.4 (C), 59.3 (C), 39.7 (CH ), 39.5 (CH ), 39.2 (CH ), 37.86 (CH ), 36.0
1
H NMR (300 MHz, CDCl ): δ = 7.37–7.28 (m, 6 H), 7.23–7.18 (m, 4 H),
3
5.27 (s, 1 H, OH), 4.56 (d, J = 2.2 Hz, 1 H), 4.39 (dd, J = 13.7, 2 Hz, 1 H),
2
2
2
2
3.71 (s, 3 H), 2.96 (t, J = 13.6 Hz, 1 H), 2.39–2.33 (m, 2 H), 2.31–2.24
(CH ), 35.9 (CH ), 34.5 (CH), 33.1 (CH ), 33.1 (CH ), 31.0 (CH ), 20.9
2 2 2 2 2
(m, 1 H), 2.21 (dd, J = 13, 2.2 Hz, 1 H), 1.94–1.77 (m, 2 H).
(
CH),19.36 (CH2).
13
C NMR (75 MHz, CDCl ): δ = 217.02 (C), 172.21 (C), 170.85 (C),
3
Methyl 7-(Furan-2-ylmethyl)-8-hydroxy-1,6-dioxo-10-phenyl-7-
azaspiro[4.5]decane-8-carboxylate (3ed)
139.22 (C), 138.51 (C), 129.28 (2 CH), 129.08 (2 CH), 129.04 (2 CH),
128.86 (2 CH), 128.48 (CH), 127.89 (CH), 86.16 (C), 60.61 (C), 53.63
(
CH ), 43.87 (CH), 39.98 (CH), 35.81 (CH ), 34.03 (CH ), 19.78 (CH ).
Following the general procedure, the reaction of N-(furan-2-ylmeth-
yl)-2-oxocyclopentanecarboxamide (200 mg, 0.96 mmol) with meth-
yl (E)-2-oxo-4-phenylbut-3-enoate (2d; 201 mg, 1.05 mmol) in the
presence of PS-BEMP (44 mg, 10 mol%) in THF (2 mL) at r.t. for 5 h
afforded the product 3ed as a white solid (368 mg, 98%). The crude
product was obtained with 5:1.5:1:1 dr. One diastereiosomer was
separated (silica gel chromatography).
3
2
2
2
Second fraction: one diastereomer was isolated as a yellow oil (464
mg, 48%); R = 0.48 (Et O/PE, 1:1).
f
2
1
H NMR (300 MHz, CDCl ): δ = 7.36–7.32 (m, 6 H), 7.24–7.19 (m, 5 H),
3
4
1
.62 (s, 1 H), 4.40 (dd, J = 13.8, 2.2 Hz, 1 H), 3.70 (s, 3 H), 2.97 (t, J =
3.5 Hz, 1 H), 2.40–2.33 (m, 2 H), 2.30 (dd, J = 13.2, 6.7 Hz, 1 H), 2.20
(dd, J = 13.1, 2.4 Hz, 1 H), 1.94–1.77 (m, 2 H).
First fraction: one diastereomer was isolated as a yellow solid (44 mg,
13
C NMR (75 MHz, CDCl ): δ = 216.7 (C), 172.7 (C), 171.0 (C), 138.2 (C),
3
1
2%); mp 165 °C; R = 0.56 (Et O/PE, 7:3).
f
2
137.1 (C), 129.3 (2 CH), 128.8 (2 CH), 128.6 (CH), 128.5 (CH), 128.3 (2
CH), 127.2 (2 CH), 86.1 (C), 61.4 (C), 53.5 (CH ), 39.6 (CH ), 38.0 (CH),
1
H NMR (300 MHz, CDCl ): δ = 7.23 (d, J = 0.9 Hz, 1 H), 7.19 (t, J = 5.2
3
3
2
Hz, 2 H), 7.14–7.06 (m, 2 H), 6.22 (dd, J = 3.1, 1.9 Hz, 1 H), 6.16 (d, J =
35.5 (CH ), 30.3 (CH ), 19.3 (CH ).
2 2 2
3
.2 Hz, 1 H), 4.38 (s, 2 H), 3.69 (s, 3 H), 3.64–3.53 (m, 1 H), 3.43 (dd, J =
HRMS (ESI+): m/z [M + H]+ calcd for C23H24NO : 394.1649; found:
5
13.8, 2.1 Hz, 1 H), 2.79–2.69 (m, 1 H), 2.20–1.98 (m, 2 H), 1.92–1.81
394.1661.
(m, 1 H), 1.77 (dd, J = 12.9, 2.2 Hz, 1 H), 1.68–1.55 (m, 1 H), 1.10 (d, J =
1
4.8 Hz, 1 H), 0.87–0.76 (m, 1 H).
Methyl 8-Hydroxy-3,3-dimethyl-1,6-dioxo-10-phenyl-7-aza-
spiro[4.5]decane-8-carboxylate (3gd)
13
C NMR (75 MHz, CDCl ): δ = 217.34 (C), 172.76 (C), 171.01 (C),
3
1
1
50.73 (C), 141.87 (CH), 139.16 (C), 128.93 (2 CH), 128.89 (2 CH),
27.92 (CH), 110.68 (CH), 108.76 (CH), 85.60 (COH), 60.63 (C), 54.39
Following the general procedure, the reaction of 4,4-dimethyl-2-oxo-
cyclopentanecarboxamide (170 mg, 1.09 mmol) with methyl (E)-2-
oxo-4-phenylbut-3-enoate (2d; 229.69 mg, 1.20 mmol) in the pres-
ence of PS-BEMP (49 mg, 10 mol%) in THF (2.5 mL) at r.t. for 24 h af-
forded the product 3gd as a white solid (160 mg, 42%). The crude
product was obtained with 2:2:1:1 dr; R = 0.35 (Et O). Data given are
(CH ), 43.47 (CH), 40.75 (CH ), 40.48 (CH ), 36.02 (CH ), 34.26 (CH ),
3
2
2
2
2
2
0.18 (CH2).
Second fraction: a mixture of two diastereomers was isolated (295
mg, 80%) as a yellow oil; R = 0.44 (Et O/PE, 7:3). The major diastereo-
f
2
f
2
mer partially crystallized as white needles for X-ray analysis.
for the mixture of four diastereomers.
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–O