3820
A. L. Kohnen et al. / Tetrahedron 62 (2006) 3815–3822
K1 1
602, 1380, and 1168 cm ; H NMR (500 MHz, CDCl ) d
.61 (d, JZ7.9 Hz, 2H), 7.27–7.33 (m, 5H), 7.20 (d, JZ
.3 Hz, 2H), 5.05 (s, 2H), 3.50 (s, 2H), 2.42 (s, 3H), 1.80 (t,
21
procedure provided 0.114 g of dark red oil, which was
1
7
7
3
purified by column chromatography on 6 g of silica gel
(gradient elution with 0–10% EtOAc–hexanes) to furnish
0.095 g (86%) of 21 as an orange oil: IR (neat) 2955, 2930,
JZ7.6 Hz, 2H), 1.15 (app q, JZ7.1 Hz, 4H), 0.98–1.08 (m,
1
3
K1 1
4
CDCl ) d 187.0, 157.7, 145.3, 136.0, 135.4, 130.3, 129.0,
H), and 0.79 (t, JZ7.3 Hz, 3H); C NMR (125 MHz,
2857, 1756, 1732, 1606, 1370, 1239, and 1153 cm ; H
NMR (500 MHz, CDCl ) d 7.35 (app t, JZ7.4 Hz, 2H), 7.29
3
3
1
2
28.0, 127.5, 126.8, 126.2, 52.6, 50.3, 31.4, 29.2, 28.3, 23.7,
2.5, 21.7, and 14.1; HRMS-ESI m/z [MCNa] calcd for
(app d, JZ7.3 Hz, 1H), 7.18 (d, JZ7.2 Hz, 2H), 4.96 (s,
2H), 3.56 (t, JZ1.6 Hz, 2H), 3.51 (t, JZ6.1 Hz, 2H), 2.07
(t, JZ7.6 Hz, 2H), 1.60–1.66 (m, 2H), 1.46 (s, 9H), 0.84 (s,
C
C H NO S, 434.1760; found 434.1770.
2
4
29
3
1
3
9
188.4, 160.7, 151.5, 137.0, 129.0, 127.7, 126.0, 125.7, 84.3,
H), and K0.01 (s, 6H); C NMR (125 MHz, CDCl ) d
3
4
.5.3. 3-(N-Methoxycarbonyl-N-methylamino)-2-cyclo-
buten-1-one (18). Reaction of ynamide 9 (0.456 g,
.03 mmol) in 8 mL of CH CN with ketene for 10 h
62.6, 51.4, 50.9, 31.4, 28.1, 26.1, 20.5, 18.5, and K5.1;
C
4
HRMS-EI m/z [M] calcd for C25H39NO Si, 446.2721;
4
3
according to the general procedure afforded 1.49 g of dark
brown liquid. Column chromatography on 20 g of silica gel
found 446.2737.
(
elution with 50% EtOAc–hexanes) yielded 0.496 g (80%)
of cyclobutenone 18 as a reddish-brown solid: mp 52–53 8C;
4.5.7. 4,4-Dichloro-2-hexyl-3-[N-(methoxycarbonyl)-N-
methylamino]-2-cyclobuten-1-one (11). A one-necked,
10 mL, pear flask fitted with a rubber septum and an
argon inlet needle was charged with ynamide 6 (0.100 g,
0.507 mmol) in 1.7 mL of Et O and cooled to 0 8C. Zinc–
2
copper couple (0.149 g, 2.28 mmol) was then added in one
portion followed by a solution of trichloroacetyl chloride
K1
IR (CH Cl ) 2960, 1741, 1570, 1445, 1365, and 1226 cm
;
H NMR (400 MHz, CDCl ) d 5.16 (s, 1H), 3.71 (s, 3H),
2
2
1
3
1
3
.42 (s, 2H), and 3.25 (s, 3H); C NMR (125 MHz, CDCl3)
3
d 184.3, 166.4, 153.1, 112.2, 49.9, and 34.7; HRMS-ESI m/z
[
C
MCNa] calcd for C H NO , 178.0475; found 178.0472.
7 9 3
(0.17 mL, 0.276 g, 1.52 mmol) in 0.5 mL of DME dropwise
via syringe over 15 min. The reaction mixture was allowed
to warm to rt over 3.5 h, diluted with 10 mL of Et O, and
2
4.5.4. 3-[N-(3-Butenyl)-N-(methoxycarbonyl)amino]-2-
isopropenyl-2-cyclobuten-1-one (19). Reaction of ynamide
8
solvent for 44 h according to the general procedure
provided 0.166 g of dark red oil, which was purified by
column chromatography on 10 g of silica gel (gradient
elution with 0–20% EtOAc–hexanes) to furnish 0.087 g
(0.109 g, 0.564 mmol) with ketene in the absence of
then extracted with 4 mL of ice-cold 0.5 M HCl solution
followed by 4 mL of ice-cold 5% NaOH solution. The
combined aqueous layers were extracted with two 5-mL
portions of Et O, and the combined organic phases were
2
washed with 10 mL of brine, dried over MgSO , filtered,
4
2
1
(
1
(
65%) of 19 as a pale yellow oil: IR (neat) 2958, 1737, 1642,
595, 1416, 1390, 1368, and 1220 cm
and concentrated to give 0.165 g of dark yellow oil. Column
chromatography on 10 g of silica gel (elution with 10%
EtOAc–hexanes) afforded 0.138 g (88%) of cyclobutenone
K1
1
;
H NMR
500 MHz, CDCl ) d 5.66–5.75 (m, 1H), 5.17 (qn, JZ
3
1
4
2
.6 Hz, 1H), 5.08–5.10 (m, 1H), 5.06 (app t, JZ1.4 Hz, 1H),
.89–4.91 (m, 1H), 3.87–3.91 (m, 2H), 3.86 (s, 3H), 3.51 (s,
H), 2.31–2.36 (m, 2H), and 1.94 (dd, JZ1.5, 1.1 Hz, 3H);
11 as a yellow oil: IR (CDCl ) 2958, 2931, 1785, 1754,
3
K1
1601, 1448, 1384, and 1295 cm ; H NMR (500 MHz,
1
CDCl ) d 3.94 (s, 3H), 3.61 (s, 3H), 2.35 (t, JZ6.7 Hz, 2H),
3
1
3
C NMR (125 MHz, CDCl ) d 185.8, 157.9, 153.3, 134.6,
133.6, 127.9, 117.9, 117.8, 54.2, 51.1, 46.6, 32.9, and 22.3;
HRMS-EI m/z [M] calcd for C H NO , 236.1281; found
1.55–1.56 (m, 2H), 1.26–1.32 (m, 6H), 0.88 (t, JZ6.7 Hz,
3
1
3H); C NMR (100 MHz, CDCl ) d 180.1, 163.0, 152.9,
3
3
C
133.1, 88.6, 54.7, 35.1, 31.5, 29.7, 29.2, 24.9, 22.6, and
14.1; HRMS-EI m/z [M] calcd for C H Cl NO ,
1
3
17
3
C
2
36.1291.
1
3
19
2
3
3
07.0737; found 307.0749.
4
2
1
.5.5. 3-[N-Methoxycarbonyl-N-(2-phenylethyl)amino]-
-phenyl-2-cyclobuten-1-one (20). Reaction of ynamide
5 (0.100 g, 0.377 mmol) with ketene in the absence of
4.5.8.
2-Hexyl-3-[N-(methoxycarbonyl)-N-methyl-
amino]-4-phenylsulfanyl-2-cyclobuten-1-one (12). A
25 mL, two-necked, pear flask equipped with a rubber
septum and a reflux condenser fitted with an argon inlet
adapter was charged with ynamide 6 (0.100 g, 0.507 mmol),
6 mL of CH Cl , and Rh (OAc) (0.002 g, 0.005 mmol).
2
1
solvent for 42 h according to the general procedure
provided 0.125 g of dark red oil, which was purified by
column chromatography on 6 g of silica gel (gradient
elution with 0–20% EtOAc–hexanes) to furnish 0.078 g
2
2
2
4
(
(
67%) of 20 as a pale yellow solid: mp 99–101 8C; IR
CH Cl ) 3028, 2956, 2361, 1749, 1735, 1619, 1590, and
The rubber septum was replaced with a 5 mL addition
funnel, which was then charged with a solution of
PhSCOCHN (0.145 g, 0.811 mmol) in 1.5 mL of CH Cl .
2
2
K1
1
399 cm ; H NMR (500 MHz, CDCl ) d 7.35–7.41 (m,
1
3
6
(
(
1
4
3
3
2
2
2
H), 7.31 (app d, JZ0.9 Hz, 2H), 7.16 (t, JZ2.6 Hz, 3H),
.67 (dd, JZ5.8, 2.4 Hz, 2H), 3.94 (t, JZ7.8 Hz, 2H), 3.83
The green reaction mixture was heated at reflux and the
diazo thiol ester solution was added dropwise over 1 h (the
funnel was rinsed with 0.5 mL of CH Cl ). The resulting
1
3
s, 3H), 3.59 (s, 2H), and 2.74 (t, JZ7.8 Hz, 2H); C NMR
2
2
125 MHz, CDCl ) d 185.7, 158.8, 153.4, 137.3, 129.6,
mixture was heated at reflux for an additional 20 min and
then allowed to cool to rt. The reaction mixture was
concentrated and the resulting brown oil was filtered
through a column of 2 g of silica gel with the aid of
3
29.3, 128.9, 128.7, 128.6, 128.3, 127.0, 126.4, 54.4, 51.8,
9.4, and 34.9; HRMS-EI m/z [M] calcd for C H NO ,
22.1438; found 322.1446.
C
2
0
19
3
4
0 mL of CH Cl . The filtrate was concentrated to give
2 2
4
.5.6. 3-[N-Benzyl-N-(tert-butoxycarbonyl)amino]-2-(3-
0.244 g of orange oil, which was purified by column
chromatography on 10 g of silica gel (elution with 10%
EtOAc–hexanes) to give 0.133 g (76%) of 12 as an orange
tert-butyldimethylsiloxybutyl)-2-cyclobuten-1-one (21).
Reaction of ynamide 16 (0.100 g, 0.248 mmol) in 0.5 mL
of CH CN with ketene for 10 h according to the general
K1
oil: IR (neat) 2956, 2929, 1758, 1738, 1612, and 1379 cm
;
3