Molina et al.
(thin film) νmax 1736, 1501, 1453 cm-1
;
13C NMR (500 MHz, CD2-
(125 MHz, CD2Cl2) δ 193.0, 151.7, 145.9, 139.0, 138.7, 133.3,
129.3, 129.0, 128.3, 126.4, 123.3, 115.7, 113.1, 47.1, 37.1, 31.1,
30.6, 25.5; HRMS (ES) m/z calcd for C22H24N2O [M + Na]+
355.1786, found 355.1785.
Cl2) δ 195.4, 152.4, 133.7, 133.7, 129.9, 123.7, 34.9, 18.3; HRMS
(ES) m/z calcd for C10H12N2O [M + H]+ 177.0950, found 177.9038.
Ethyl(phenyl)azocarboxylate (13c). To a solution of hydrazide
12c15 (0.15 g, 0.832 mmol) in dry CH2Cl2 was added n-Bu4NIO4
(1.3 equiv, 0.469 g, 1.08 mmol) and the solution was stirred at
room temperature for 5 h (TLC monitoring). Flash column
chromatography (1:2 EtOAc:hexanes) of the crude product yielded
0.14 g (95%) of N-acyl azo 13c as a red oil: 1H NMR (400 MHz,
CDCl3) δ 7.94 (m, 2H), 7.56 (m, 3H), 4.53 (q, 2H), 1.48 (t, J )
7.1 Hz, 3H); IR (thin film) 2986, 1755, 1503; 13C NMR (500 MHz,
CDCl3) δ 162.4, 151.8, 134.0, 129.5, 123.9, 64.7, 14.4; HRMS (ES)
m/z calcd for C9H10N2O2 [M + Na] 201.0640, found 201.0639.
3-Benzyl-9-phenyl-1,9-diazabicyclo[4.3.1]dec-6-en-2-one (24).
To a cooled (0 °C) solution of hydrazide 21 (0.24 g, 0.75 mmol)
in CH2Cl2 was added n-Bu4NIO4 (1.3 equiv, 0.42 g, 97 mmol) and
the solution was stirred at 25 °C. After 24 h (TLC monitoring), the
reaction mixture was diluted with CH2Cl2 (10 mL) and washed
with saturated Na2SO3 (2 × 10 mL). The organic layers were
combined, dried over Na2SO4, filtered, and concentrated in vacuo.
Flash column chromatography (1:3 EtOAc:hexanes) of the crude
product afforded cycloadduct 24 (0.22 g, 91%) as a pale yellow
solid: 1H NMR (500 MHz, CDCl3) δ 7.31-7.24 (m, 7H), 6.95
(app d, J ) 7.9 Hz, 2H), 6.87 (app t, J ) 7.3 Hz, 1H), 5.83 (br s,
1H), 4.33 (dd, J ) 13.8, 7.3 Hz, 1H), 4.20 (d, J ) 14.7, 1H), 3.49
(d, J ) 14.5 Hz, 1H), 3.40 (m, 1H), 3.22-3.17 (m, 2H), 2.61 (dd,
J ) 14.1, 7.7 Hz, 1H), 2.53 (dd, J ) 12.3, 6.9 Hz, 1H), 2.39 (m,
1H), 2.17 (d, J ) 11.7 Hz, 1H), 1.74 (m, 1H); IR (thin film) 2930,
General Procedure for the T2IMDA Reaction with N-Acylazo
Dienophiles Catalyzed by ZnCl2. To a cooled solution (-78 °C)
of N-acylazo dienophile (0.01 M) in CH2Cl2 was added ZnCl2 (10
mol %) as a solid in one portion. After 2 h, the reaction mixture
was gradually allowed to warm to 25 °C and was completed after
3 h (monitored by TLC). The solution was diluted with CH2Cl2
and poured in H2O. The layers were separated and the aqueous
layer was extracted with 3 portions of CH2Cl2. The combined
organic layers were washed with NaHCO3 and brine then dried
over Na2SO4. The organic layer was concentrated in vacuo.
10-Phenyl-1,10-diazabicyclo[5.3.1]undec-7-en-2-one (15). To
a solution of N-acylazo dienophile 14 (0.0960 g, 0.396 mmol) in
CH2Cl2 (10 mL) was added ZnCl2 (0.0054 g, 0.0396 mmol).
Purification of the crude product by column chromatrography (1:3
EtOAc:hexanes) afforded cycloadduct 15 (0.075 g, 78% yield) as
a pale yellow solid: 1H NMR (500 MHz, CDCl3) δ 7.26 (app t, J
) 7.8 Hz, 2H), 6.90 (app d, J ) 8.7 Hz, 2H), 6.81 (app t, J ) 7.3
Hz, 1H), 5.55 (br s, 1H), 4.20 (d, J ) 5.2 1H), 4.15 (d, J ) 15.5
Hz, 1H), 3.96 (br d, J ) 15.7, 1H), 3.56 (br d, J ) 15.8 Hz, 1H),
2.62 (dd, J ) 13.1, 9.3, 1H), 2.52 (m, 1H), 2.41 (t, J ) 11.5, 1H),
2.15-2.10 (m, 3H), 1.90 (m, 1H), 1.44 (m, 1H); IR (thin film)
νmax 2932, 1656, 1599, 1497 cm-1 13C NMR (125 MHz, CDCl3)
;
δ 180.5, 148.7, 141.7, 129.2, 121.9, 118.7, 112.0, 47.5, 47.1, 37.6,
33.7, 27.2, 24.4; HRMS (ES) m/z calcd for C15H18N2O [M + Na]+
265.1317, found 265.1308.
1694, 1598,1495 cm-1 13C NMR (125 MHz, CDCl3) δ184.7, 150.7,
;
149.9, 140.5, 129.7, 129.4, 128.8, 126.7, 120.48, 119.7, 114.9, 51.0,
49.3, 46.6, 39.5, 38.9, 34.6. HRMS (ES) m/z calcd for C21H22N2O
[M + H]+ 319.1810, found 319.1810.
3-Benzyl-10-phenyl-1,10-diazabicyclo[5.3.1]undec-7-en-2-
one (30). To a solution of N-acylazo dienophile 29 (0.087 g, 0.26
mmol) in CH2Cl2 (7 mL) was added ZnCl2 (0.0036 g, 0.011 mmol).
Purification of the crude product by column chromatrography (1:4
EtOAc:hexanes) afforded cycloadduct 30 (0.062 g, 71% yield) as
a pale yellow oil: 1H NMR (500 MHz, CDCl3) δ. δ 7.31-7.18 (m
overlapped, 7H), 6.76 (app t, J ) 7.3 Hz, 1H), 6.64 (app d, J )
8.8 Hz, 2H), 5.66 (br s, 1H), 4.24 (d, J ) 15.6, 1H), 4.13 (dd, J )
15.5, 5.1, 1H), 3.98 (dt, J ) 15.6, 2.1 Hz, 1H), 3.55 (br d, J )
15.6, 1H), 3.20 (dd, J ) 13.5, 8.5, 1H), 2.76 (m, 1H), 2.66 (dd, J
) 13.5, 6.4 Hz, 1H), 2.49 (br m, 1H), 2.17-2.05 (m, 2H), 1.87
(m, 2H), 1.4 (m, 1H); IR (thin film) νmax 2930, 1698, 1598, 1497
General Procedure for the Preparation of N-Acyl Azo
Dienophiles with NBS.16 To a solution of a hydrazide in CH2Cl2
was added pyridine (1 equiv). The reaction mixture was cooled to
0 °C and N-bromosuccinimide (1 equiv) was added to the solution.
After 2 h, the orange reaction mixture was poured into H2O. The
layers were separated and the aqueous layer was extracted with 3
portions of CH2Cl2. The combined organic layers were washed with
5% HCl, 10% K2CO3, and brine and dried over Na2SO4. The organic
layer was concentrated in vacuo.
cm-1 13C NMR (125 MHz, CDCl3) δ 181.9, 148.3, 140.8, 140.1,
;
6-Methyleneoct-7-enoic Acid Azobenzene (14). To a solution
of hydrazide 9 (0.101 g, 0.413 mmol) in CH2Cl2 (5 mL) was added
pyridine (0.033 g, 0.417 mmol). The reaction mixture was cooled
to 0 °C and N-bromosuccinimide (0.074 g, 0.416 mmoles) was
added to the solution. The organic layer was concentrated in vacuo
to give 0.096 g of N-azo dienophile 14 in 96% yield and was used
without further purification: 1H NMR (500 MHz, CDCl3) δ 7.89
(app d, J ) 7.1 Hz, 2H), 7.60-7.51 (m overlapped, 3H), 6.37 (dd,
J ) 17.6, 10.8 Hz, 1H), 5.23 (d, J ) 17.6 Hz, 1H), 5.08 (d, J )
10.8 Hz, 1H), 5.4 (s, 1H), 5.2 (s, 1H), 2.77 (t, J ) 7.3 Hz, 2H),
2.27 (t, J ) 7.7 Hz, 2H), 1.82 (m, 2H), 1.63 (m, 2H); IR (thin
129.4, 128.9, 128.3, 126.2, 122.4, 118.3, 111.6, 48.5, 47.6, 46.7,
40.6, 33.9, 31.4, 27.0; HRMS (ES) m/z calcd for C22H24N2O [M +
H]+ 333.1967, found 333.1963.
General Procedure for the Hydrogenation of the Bridgehead
Alkene. To a solution of a cycloadduct in EtOH was added 10%
Pd/C. The reaction mixture was stirred under 1 atm or 50 psi of H2
for 5 h. The catalyst was filtered through celite and the filtrate was
concentrated in vacuo.
9-Phenyl-1,9-diazabicyclo[4.3.1]decan-2-one (16). To a solution
of cycloadduct 11 (0.025, 0.011 mmol) in EtOH (5 mL) was added
10% Pd/C (0.003 g). The reaction mixture was stirred under 1 atm
of H2 for 5 h. The clear oil was purified by column chromatography
(1:1 EtOAc:hexanes) to afford 16 (0.023 g, 92% yield): 1H NMR
(500 MHz, CDCl3) δ 7.26 (m, 2H), 6.91-6.89 (m, 3H), 3.8 (ddd,
J ) 9.7, 9.7, 5.3 Hz, 1H), 3.7 (d, J ) 14.9 Hz, 1H), 3.24-3.18 (m,
2H), 2.92 (m, 1H), 2.59 (dt, J ) 13.7, 4.4 Hz, 1H), 2.18 (m, 1H),
1.98-1.80 (m, 5H), 1.69-1.64 (m, 1H); 13C NMR (125 MHz,
CDCl3) δ 178.7, 149.3, 129.2, 120.3, 114.1, 49.2, 45.7, 35.4, 31.0,
film) νmax 2941, 1743, 1499 cm-1 13C NMR (125 MHz, CDCl3) δ
;
191.5, 151.7, 145.9, 138.9, 133.5, 129.4, 123.6, 116.1, 113.4, 34.2,
31.2, 27.7, 23.4; HRMS (ES) m/z calcd for C15H18N2O [M + Na]+
265.1317, found 265.1324.
2-Benzyl-6-methyleneoct-7-enoic Acid Azobenzene (29). To
a solution of hydrazide 23 (0.023 g, 0.069 mmol) in CH2Cl2 (2
mL) was added pyridine (0.0054 g, 0.0687 mmol). The reaction
mixture was cooled to 0 °C and N-bromosuccinimide (0.0122 g,
0.0688 mmol) was added to the solution. The organic layer was
concentrated under vacuo to give N-acylazo dienophile 29 (0.0215
g) in 94% yield and used without further purification: 1H NMR
(500 MHz, CD2Cl2) δ 7.82 (app d, J ) 7.5 Hz, 2H), 7.58-7.55 (m
overlapped, 3H), 7.28-7.20 (m, 5H), 6.35 (dd, J ) 17.6, 10.8 Hz,
1H), 5.20 (d, J ) 17.6 Hz, 1H), 5.05 (d, J ) 10.9 Hz, 1H), 4.98 (s,
1H), 4.95 (s, 1H), 3.31 (m, 1H), 3.12 (dd, J ) 13.8, 7.7 Hz, 1H),
2.88 (dd, J ) 13.8, 6.7, 1H), 2.18 (m, 2H), 1.83 (m, 1H), 1.65-
1.53 (m, 3H); IR (thin film) νmax 2941, 1735, 1594, 1498; 13C NMR
30.6, 22.9, 19.7; IR (thin film) νmax 2933, 1682, 1599, 1495 cm-1
;
HRMS (ES) m/z calcd for C14H18N2O [M + H]+ 231.1497, found
231. 1498.
10-Phenyl-1,10-diazabicyclo[5.3.1]undecan-2-one (18). To a
solution of cycloadduct 15 (0.041, 0.17 mmol) in EtOH (5 mL)
was added 10% Pd/C (0.004 g). The reaction mixture was stirred
under 1 atm of H2 for 5 h. The clear oil was purified by column
chromatography (1:1 EtOAc:hexanes) to afford 18 (0.036 g, 89%
yield): 1H NMR (500 MHz, CDCl3) δ 7.246 (m, 2H), 6.88-6.82
6822 J. Org. Chem., Vol. 72, No. 18, 2007