Highly diastereoselective synthesis of cyclopentenones via a one-pot gold catalysis, Nazarov cyclization and alkylation cascade

Article abstract of DOI:10.1055/s-0033-1341204

Starting from readily available propargylic carboxylates, three sequential transformations [gold-catalyzed tandem reaction, scandium(III) trifluoromethanesulfonate catalyzed Nazarov cyclization, alkylation reaction] in a one-pot process led to the formation of cyclopentenone derivatives in excellent diastereoselectivities and moderate to good overall yields. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0033-1341204

SYNTHESIS
Journal of Synthetic 0rganic Chemistry
SUPPORTING INFORMATION
Supporting Information
for DOI: 10.1055/s-0033-1341204
Georg Thieme Verlag KG Stuttgart · New York 2014
©
Thieme

Supporting Information
Highly Diastereoselective Synthesis of Cyclopentenones via a One-Pot
Gold CatalysisꢀꢁNazarov CyclizationꢁDQGꢁAlkylation Cascade
Meng-Qi Liu, Ai-Hua Zhou, Shuang Jiang, Jia-Qi Wang, Long-Wu Ye*
State Key Laboratory for Physical Chemistry of Solid Surfaces, The Key Laboratory for
Chemical Biology of Fujian Province and Department of Chemistry, College of
Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, Fujian, P. R.
China
Content•
ꢀ Pageꢀnumberꢀ
General
2
2
Preparation of Starting Materials
1
13
H and C NMR spectra
11

General Information. Ethyl acetate (ACS grade), hexanes (ACS grade) and toluene
(
ACS grade) were obtained commercially and used without further purification.
Methylene chloride, tetrahydrofuran and diethyl ether were purified according to standard
methods unless otherwise noted. Commercially available reagents were used without
further purification. Reactions were monitored by thin layer chromatography (TLC) using
silicycle pre-coated silica gel plates. Flash column chromatography was performed over
silica gel (300-400 mesh). Infrared spectra were recorded on a Nicolet AVATER
-1
FTIR330 spectrometer as thin film and are reported in reciprocal centimeter (cm ).
1H NMR spectra were recorded on a Bruker AV-400 spectrometer and a Bruker AV-
5
00 spectrometer in chloroform-d . Chemical shifts are reported in ppm with the internal
3
TMS signal at 0.0 ppm as a standard. The data is being reported as (s = singlet, d =
doublet, t = triplet, m = multiplet or unresolved, brs = broad singlet, coupling constant(s)
in Hz, integration).
13C NMR spectra were recorded on on a Bruker AV-400 spectrometer and a Bruker
AV-500 spectrometer in chloroform-d . Chemical shifts are reported in ppm with the
3
internal chloroform signal at 77.0 ppm as a standard.
Representative synthetic procedures for the preparation of propargylic carboxylates
11-2
1
-(4-bromophenyl)hept-2-yn-1-yl 3,4-dihydro-2H-pyran-6-carboxylate (1a)

1
a
1H NMR (400 MHz, CDCl
) ꢀ 7.49 (d, 2H, J = 13.2 Hz), 7.42 (d, 2H, J = 12.4 Hz), 6.52
3
(
t, 1H, J = 2 Hz), 6.10 (t, 1H, J = 4.4 Hz), 4.10 (t, 2H, J = 5.6 Hz), 2.28 – 2.24 (m, 2H),
2
.19 – 2.15 (m, 2H), 1.87 – 1.81 (m, 2H), 1.55 – 1.48 (m, 2H), 1.44 – 1.34 (m, 2H), 0.90
13
(
t, 3H, J = 7.2 Hz); C NMR (100 MHz, CDCl
3
) ꢀ 161.8, 144.0, 136.6, 131.7, 129.5,
1
2
22.9, 112.3, 89.1, 75.9, 66.7, 65.8, 30.4, 22.0, 21.4, 20.7, 18.6, 13.6; IR (neat): 3469(bs),
957, 2932, 2872, 2234, 1745(s), 1645, 1487, 1262, 1163, 1108, 1070, 910, 747; HRMS
+
(
EI): m/z [M ] calcd for C19
H
21BrO : 376.0674; found: 376.0676.
3
1-(4-chlorophenyl)hept-2-yn-1-yl 3,4-dihydro-2H-pyran-6-carboxylate (1b)
1
b
1H NMR (500 MHz, CDCl
) ꢀ 7.50 – 7.47 (m, 2H), 7.35 – 7.32 (m, 2H), 6.54 (t, 1H, J =
3
2
2
.0 Hz), 6.10 (t, 1H, J = 4.0 Hz), 4.09 (t, 2H, J = 5.5 Hz), 2.28 – 2.25 (m, 2H), 2.19 –
.15 (m, 2H), 1.87 – 1.82 (m, 2H), 1.55 – 1.49 (m, 2 H), 1.44 – 1.36 (m, 2H), 0.91 (t, 3H,
13
J = 7.5); C NMR (125 MHz, CDCl
3
) ꢀ 161.8, 144.1, 136.1, 134.6, 129.2, 128.7, 112.3,
8
2
9.1, 76.0, 66.7, 65.8, 30.4, 21.9, 21.4, 20.7, 18.5, 13.5; IR (neat): 3490(bs), 2957, 2932,
+
870, 2228, 1743(s), 1642, 1594, 1491, 1259, 912, 818, 744; HRMS (EI): m/z [M ] calcd
for C H ClO : 332.1179; found: 332.1178.
1
9
21
3
1
-(4-fluorophenyl)hept-2-yn-1-yl 3,4-dihydro-2H-pyran-6-carboxylate (1c)

1
c
1H NMR (400 MHz, CDCl
) ꢀ 7.55 – 7.51 (m, 2H), 7.06 – 7.02 (m, 2H), 6.55 (s, 1H),
.09 (t, 1H, J = 4.4 Hz), 4.09 (t, 2H, J = 5.2 Hz), 2.28 – 2.24 (m, 2H), 2.18 – 2.14 (m,
H), 1.86 – 1.81 (m, 2H), 1.55 – 1.48 (m, 2H), 1.44 – 1.35 (m, 2H), 0.90 (t, 3H, J = 7.2
3
6
2
1
3
Hz); C NMR (100 MHz, CDCl
3
) ꢀ 171.0, 162.7 (d, J = 236.3 Hz), 144.1, 133.5, 129.8
(d, J = 8.4 Hz), 115.4 (d, J = 21.6 Hz), 112.2, 88.9, 76.4, 66.7, 65.8, 30.4, 22.0, 21.4, 20.7,
1
1
3
8.5, 13.5; IR (neat): 3445(bs), 2957, 2934, 2873, 2228, 1731(s), 1647, 1606, 1510, 1258,
+
217, 1108, 913, 743; HRMS (EI): m/z [M ] calcd for C19
H
21FO : 316.1475; found:
3
16.1477.
1
-phenylhept-2-yn-1-yl 3,4-dihydro-2H-pyran-6-carboxylate (1d)
1
d
1H NMR (400 MHz, CDCl
)ꢁꢀ 7.56 – 7.53 (m, 2H), 7.39 – 7.31 (m, 3H), 6.58 (t, 1H, J =
3
1
2
.6 Hz), 6.10 (t, 1H, J = 4.0 Hz), 4.09 (t, 2H, J = 5.2 Hz), 2.28 – 2.24 (m, 2H), 2.18 –
.13 (m, 2H), 1.86 – 1.80 (m, 2H), 1.55 – 1.48 (m, 2H), 1.44 – 1.35 (m, 2H), 0.90 (t, 3H,
1
3
J = 7.2 Hz); C NMR (100 MHz, CDCl
3
) ꢀ 161.9, 144.2, 137.5, 128.7, 128.5, 127.8,
12.1, 88.7, 76.4, 66.7, 66.5, 30.5, 22.0, 21.4, 20.7, 18.9, 13.6; IR (neat): 2959, 2933,
872, 2231, 1732(s), 1647, 1295, 1258, 1216, 1109, 913, 826; HRMS (EI): m/z [M+]
: 298.1569; found: 298.1568.
1
2
calcd for C19
H
22
O
3

1
-(p-tolyl)hept-2-yn-1-yl 3,4-dihydro-2H-pyran-6-carboxylate (1e)
1
e
1H NMR (500 MHz, CDCl
) ꢀ 7.45 – 7.43 (m, 2H), 7.18 – 7.16 (m, 2H), 6.55 (t, 1H, J =
3
2
2
Hz), 6.08 (t, 1H, J = 4.5 Hz), 4.08 (t, 2H, J = 5.5 Hz), 2.35 (s, 3H), 2.28 – 2.25 (m, 2H),
.19 – 2.15 (m, 2H), 1.87 – 1.82 (m, 2H), 1.55 – 1.49 (m, 2H), 1.44 – 1.36 (m, 2H), 0.91
1
3
(
t, 3H, J = 7.5 Hz); C NMR (125 MHz, CDCl
3
) ꢀ 161.9, 144.2, 138.6, 134.7, 129.2,
1
3
8
27.8, 111.9, 88.4, 76.6, 66.6, 66.4, 30.5, 22.0, 21.4, 21.2, 20.7, 18.6, 13.6; IR (neat):
498(bs), 2957, 2933, 2873, 2231, 2096, 1746(s), 1648, 1510, 1259, 1216, 1109, 913,
+
13; HRMS (EI): m/z [M ] calcd for C20
H
24
3
O : 312.1725; found: 312.1727.
1
-(4-isopropylphenyl)hept-2-yn-1-yl 3,4-dihydro-2H-pyran-6-carboxylate (1f)
1
f
1H NMR (400 MHz, CDCl
) ꢀ 7.47 (d, 2H, J = 8.4 Hz), 7.22 (d, 2H, J = 8.4 Hz, ), 6.55 (t,
3
1
2
–
H, J = 1.6 Hz), 6.09 (t, 1H, J = 4.0 Hz), 4.08 (t, 2H, J = 5.2 Hz), 2.94 – 2.87 (m, 1H),
.28 – 2.24 (m, 2H), 2.17 – 2.13 (m, 2H), 1.85 – 1.80 (m, 2H), 1.55 – 1.48 (m, 2H), 1.45
1
3
1.36 (m, 2H), 1.24 (d, 6H, J = 6.8 Hz), 0.90 (t, 3H, J = 7.2 Hz); C NMR (100 MHz,
) ꢀ 162.0, 149.5, 144.2, 134.9, 127.9, 126.6, 112.0, 88.4, 76.6, 66.7, 66.5, 33.9,
0.5, 23.9, 22.0, 21.4, 20.7, 18.6, 13.6; IR (neat): 3445(bs), 2957, 2933, 2873, 2099,
CDCl
3
3

+
1
3
732(s), 1645, 1294, 1260, 1216, 1109, 913; HRMS (EI): m/z [M ] calcd for C22
H
28
O :
3
40.2038; found: 340.2038.
1
-(2-bromophenyl)hept-2-yn-1-yl 3,4-dihydro-2H-pyran-6-carboxylate (1g)
1
g
1H NMR (400 MHz, CDCl
) ꢀ 7.81 – 7.79 (m, 1H), 7.57 – 7.55 (m, 1H), 7.38 – 7.34 (m,
3
1
H), 7.23 – 7.19 (m, 1H), 6.76 (t, 1H, J = 2.0 Hz), 6.09 (t, 1H, J = 4.0 Hz), 4.10 (t, 2H, J
=
5.2 Hz), 2.28 – 2.24 (m, 2H), 2.19 – 2.15 (m, 2H), 1.89 – 1.82 (m, 2H), 1.55 – 1.48 (m,
1
3
2
1
2
1
H), 1.44 – 1.35 (m, 2H), 1.90 (t, 3H, J = 7.2 Hz); C NMR (100 MHz, CDCl ) ꢀ 161.6,
3
44.0, 136.7, 133.0, 130.2, 129.8, 127.6, 123.5, 112.1, 89.2, 75.6, 66.7, 66.1, 30.4, 22.0,
1.4, 20.7, 18.6, 13.6; IR (neat): 2930, 2871, 2228, 1732, 1646, 1465, 1255, 1214, 1106,
+
068, 913, 745; HRMS (EI): m/z [M ] calcd for C19
H
21BrO : 376.0674; found: 376.0676.
3
1
-(o-tolyl)hept-2-yn-1-yl 3,4-dihydro-2H-pyran-6-carboxylate (1h)
nBu
O
O
O
Me
1
h
1H NMR (400 MHz, CDCl
) ꢀꢁ7.65 – 7.62 (m, 1H), 7.24 – 7.15 (m, 3H), 6.65 (t, 1H, J =
3
2
2
0
1
.0 Hz), 6.09 (t, 1H, J = 4.0 Hz), 4.09 (t, 2H, J = 5.2 Hz), 2.41 (s, 3H), 2.26 – 2.22 (m,
H), 2.19 – 2.14 (m, 2H), 1.87 – 1.82 (m, 2H), 1.54 – 1.47 (m, 2H), 1.43 – 1.34 (m, 2H),
1
3
.89 (t, 3H, J = 7.2 Hz). C NMR (100 MHz, CDCl
3
) ꢀ 161.8, 144.1, 136.4, 135.5, 130.7,
28.7, 128.1, 126.1, 112.0, 88.5, 76.3, 66.7, 64.7, 30.5, 22.0, 21.4, 20.7, 19.1, 18.6, 13.6;

IR (neat): 2956, 2932, 2872, 2228, 1731(s), 1646, 1464, 1294, 1256, 1215, 1108, 1068,
+
9
13; HRMS (EI): m/z [M ] calcd for C20
H
24
3
O : 312.1725; found: 312.1727.
1
-(m-tolyl)hept-2-yn-1-yl 3,4-dihydro-2H-pyran-6-carboxylate (1i)
1
i
1H NMR (500 MHz, CDCl
) ꢀꢁ7.64 – 7.62 (m, 1H), 7.24 – 7.15 (m, 3H), 6.65 (t, 1H, J =
3
2
2
0
1
.0 Hz), 6.09 (t, 1H, J = 4.0 Hz), 4.09 (t, 2H, J = 5.0 Hz), 2.41 (s, 3H), 2.26 – 2.22 (m,
H), 2.18 – 2.15 (m, 2H), 1.85 – 1.82 (m, 2H), 1.53 – 1.47 (m, 2H), 1.42 – 1.35 (m, 2H),
1
3
.89 (t, 3H, J = 7.5 Hz). C NMR (125 MHz, CDCl
3
) ꢀ 161.8, 144.2, 136.4, 135.6, 130.7,
28.7, 128.1, 126.1, 111.9, 88.5, 76.3, 66.7, 64.7, 30.5, 22.0, 21.4, 20.7, 19.1, 18.6, 13.5;
IR (neat): 2956, 2932, 2872, 2236, 1731(s), 1647, 1258, 1215, 1108, 913; HRMS (EI):
+
m/z [M ] calcd for C20
H
24
3
O : 312.1725; found: 312.1727.
5
-methyl-1-phenylhex-2-yn-1-yl 3,4-dihydro-2H-pyran-6-carboxylate (1j)
1
j
1
H NMR (400 MHz, CDCl ) ꢀꢁ7.56 – 7.53 (m, 2H), 7.38 – 7.30 (m, 3H), 6.59 (t, 1H, J =
3
2
.0 Hz), 6.09 (t, 1H, J = 4.0 Hz), 4.08 (t, 2H, J = 4.8 Hz), 2.16 (m, 4H), 1.88 – 1.79 (m,
1
3
3
1
3
9
H), 0.97 (d, 6H, J = 6.8 Hz); C NMR (100 MHz, CDCl ) ꢀ 161.9, 144.2, 137.5, 128.7,
3
28.5, 127.7, 112.1, 87.7, 76.8, 66.7, 66.5, 28.0, 27.9, 22.0, 21.4, 20.6; IR (neat):
436(bs), 2958, 2931, 2872, 2236, 2099, 1732(s), 1646, 1456, 1258, 1216, 1109, 1069,
+
13; HRMS (EI): m/z [M ] calcd for C19
H
22
3
O : 298.1569; found: 298.1571.

6
-methyl-1-phenylhept-2-yn-1-yl 3,4-dihydro-2H-pyran-6-carboxylate (1k)
O
O
O
Ph
1
k
1H NMR (400 MHz, CDCl
) ꢀ 7.55 – 7.53 (d, 2H), 7.38 – 7.31 (m, 3H), 6.57 (s, 1H),
3
6
2
.10 (t, 1H, J = 4.0 Hz), 4.09 (t, 2H, J = 5.2 Hz), 2.28 – 2.24 (m, 2H), 2.18 – 2.14 (m,
H), 1.86 – 1.81 (m, 2H), 1.70 – 1.61 (m, 1H), 1.46 – 1.41 (m, 2H), 0.88 (d, 6H, J = 6.8
1
3
Hz); C NMR (100 MHz, CDCl
3
) ꢀ 161.9, 144.2, 137.5, 128.7, 128.5, 127.8, 112.0, 88.8,
7
2
6.3, 66.7, 66.5, 37.3, 27.3, 22.1, 21.4, 20.6, 16.9; IR (neat): 3439(bs), 2956, 2933, 2870,
234, 2096, 1732(s), 1647, 1456, 1259, 1216, 1187, 1109, 1069, 913; HRMS (EI): m/z
+
[M ] calcd for C20
H
24
O : 312.1725; found: 312.1724.
3
6
-(benzyloxy)-1-phenylhex-2-yn-1-yl 3,4-dihydro-2H-pyran-6-carboxylate (1l)
OBn
O
O
O
Ph
1
l
1H NMR (500 MHz, CDCl
) ꢀ 7.54 – 7.51 (m, 2H), 7.37 – 7.24 (m, 8H), 6.56 (t, 1H, J =
3
2
6
.0 Hz), 6.09 (t, 1H, J = 4.0 Hz), 4.48 (s, 2H), 4.08 (t, 2H, J = 5.5 Hz), 3.55 (t, 2H, J =
13
.0 Hz ), 2.42 – 2.38 (m, 2H), 2.17 – 2.14 (m, 2H), 1.86 – 1.81 (m, 4H); C NMR (125
) ꢀ 161.9, 144.2, 138.5, 137.4, 128.7, 128.5, 128.4, 127.7, 127.6, 127.5,
12.0, 87.9, 76.8, 73.0, 68.8, 66.7,66.5, 28.6, 21.4, 20.7, 15.8; IR (neat): 3453(bs), 3032,
MHz, CDCl
3
1
2
932, 2858, 2239, 1744(s), 1645, 1495, 1454, 1259, 1109, 1075, 907, 749, 698; HRMS
+
(
EI): m/z [M ] calcd for C25
H
26
4
O : 390.1831; found: 390.1833.
6
-(1,3-dioxoisoindolin-2-yl)-1-phenylhex-2-yn-1-yl 3,4-dihydro-2H-pyran-6-
carboxylate (1m)

1
m
1H NMR (500 MHz, CDCl
H), 7.37 – 7.30 (m, 3H), 6.46 (t, 1H, J = 2.0 Hz), 6.09 (t, 1H, J = 4.0 Hz), 4.09 – 4.07
m, 2H), 3.76 (t, 2H, J = 7.0 Hz), 2.37 – 2.34 (m, 2H), 2.17 – 2.14 (m, 2H), 1.97 – 1.91
) ꢀ 7.82 – 7.80 (m, 2H), 7.69 – 7.68 (m, 2H), 7.52 – 7.51 (m,
3
2
(
(
1
3
m, 2H), 1.85 – 1.81 (m, 2H); C NMR (125 MHz, CDCl
3
) ꢀ 168.3, 161.8, 144.1, 137.2,
1
2
1
33.9, 132.1, 128.7, 128.5, 127.8, 123.2, 112.1, 87.0, 76.8, 66.6, 66.3, 37.3, 27.4, 21.4,
0.7, 16.8; IR (neat): 3460(bs), 2930, 2232, 2091, 1745(s), 1712(s), 1642, 1457, 1398,
+
265, 1110, 907; HRMS (EI): m/z [M ] calcd for C26
H
23NO : 429.1576; found: 429.1578.
5
tetradec-5-yn-7-yl 3,4-dihydro-2H-pyran-6-carboxylate (1n)
1
n
1H NMR (400 MHz, CDCl
) ꢀ 6.09 (t, 1H, J = 4.4 Hz), 5.47 – 5.43 (m, 1H), 4.11 (t, 2H, J
3
=
5.2 Hz), 2.22 – 2.17 (m, 4H), 1.89 – 1.83 (m, 2H), 1.81 – 1.73 (m, 2H), 1.52 – 1.36 (m,
1
3
6
1
2
1
3
H), 1.34 – 1.27 (m, 8H), 0.92 – 0.86 (m, 6H); C NMR (100 MHz, CDCl ) ꢀ 162.1,
3
44.3, 111.5, 86.4, 77.4, 66.6, 65.2, 35.1, 31.7, 30.5, 29.1, 29.0, 25.0, 22.6, 21.9, 21.4,
0.6, 18.4, 14.0, 13.5; IR (neat): 3493(bs), 2956, 2930, 2858, 2236, 1745(s), 1466, 1265,
+
215, 1158, 1081, 952, 748; HRMS (EI): m/z [M ] calcd for C20
H
32
3
O : 320.2351; found:
20.2353.
(E)-1-(4-bromophenyl)hept-1-en-3-one (2a')

O
nBu
Br
2
a'
1H NMR (400 MHz, CDCl
) ꢀ 7.54 – 7.39 (m, 5H), 6.73 (d, 1H, J = 16.0 Hz ), 2.65 (t,
3
13
2
H, J = 7.6 Hz), 1.70 – 1.62 (m, 2H), 1.43 – 1.33(m, 2H), 0.94 (t, 3H, J = 7.6 Hz); C
NMR (100 MHz, CDCl ) ꢀ 200.3, 140.8, 133.5, 132.1, 129.6, 126.6, 124.6, 40.8, 26.3,
3
2
2.4, 13.9. IR (neat): 2951, 2931, 1686(s), 1617, 1485, 1401, 986, 807, 479; HRMS (EI):
+
m/z [M ] calcd for C13H15BrO: 266.0306; found: 266.0308.
Reference:
1
2
. Ye, L.; Zhang, L. Org. Lett. 2009, 11, 3646.
. Cao, S.; Zhang, L. Sci. China Ser. B-Chem. 2009, 52, 1337.