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DOI: 10.1055/s-2003-39306
Diels-Alder Reactions of 4-Alkoxy-4-alkylcyclohexa-2,5-dienimines: Synthesis of 5-Alkylindoles
Publication History
Publication Date:
20 May 2003 (online)
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Abstract
N-arylsulfonyl 4-alkoxy-4-alkylcyclohexadienimines undergo thermal Diels-Alder reactions with 1,3-butadienes to yield the expected cycloadducts. The crude adducts when treated with anhydrous acid yield dihydronaphthalenes which when subjected to a series of simple transformations produce 5-alkyl indoles in good overall yields.
Key words
indoles - Diels-Alder - quinones - heterocycles
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References
The Diels-Alder reactions of N-arylsulfonyl QIK’s at ambient pressures and conversion to indoles have been studied by us will be reported in due course.
10
Typical experimental
procedure: Diels-Alder reaction. Preparation of N
-(4,8-dimethyl-5,8-dihydronaphthalen-1-yl)-4-methylbenzenesulfonamide
(
13a): The reaction mixture was prepared
by combining N-(4-methoxy-4-methylcyclohexa-2,5-dien-1-ylidene)-4methylbenzene-sulfonamide 15 (1.00g, 3.4 mmol), piperylene (0.82
g, 12.0 mmol, 1.2 mL), and a few crystals of BHT, with 5 mL dry toluene
in a sealed tube. The reaction mixture was then heated to 140 °C
for 5 days, after which time, the reaction was complete as determined
by TLC. The solvent was evaporated and the crude product was dissolved
in 50 mL THF and 3 drops of concentrated HCl were added. Once aromatization
was complete (1 h), solid NaHCO3 was added. The reaction
mixture was then dried using solid MgSO4 filtered and
concentrated. Compound 8a was then purified via
flash column chromatography to afford a white solid, (0.800 g, 2.40
mmol, 72%). Mp = 142-144 °C; 1H
NMR (400 MHz, CDCl3) δ = 7.62 (d, J = 8.2 Hz, 2 H), 7.19 (d, J = 7.0 Hz, 2 H), 6.96 (d, J = 8.2 Hz, 1 H), 6.90 (d, J = 8.2 Hz, 1 H), 6.31 (s, 1
H), 5.81 (m, 2 H), 3.34 (m, 1 H), 3.14 (m, 2 H), 2.38 (s, 3 H),
2.18 (s, 3 H), 1.06 (d, J = 6.8
Hz, 3 H); 13C NMR (100 MHz, CDCl3)
144.4, 137.5, 135.0, 134.9, 134.8, 131.7, 131.3, 130.3, 128.5, 128.0,
123.9, 122.9, 30.9, 29.0, 23.7, 22.8, 20.8; IR (thin film) = 3278,
1480, 1323, 1180
cm-1; MS m/z (relative
intensity) 328.3 (13, M + 1), 327.3 (54, M+),
172.1 (100), 155.2 (96); EIHRMS for C19H21NO2S:
found 327.1297, requires 327.1293.
Indole formation:
Preparation of {3,5-dimethyl-1-[(4-methylphenyl)sulfonyl]-1
H
-indol-4-yl}acetaldehyde (
9a). Compound 8a (0.428g,
1.30 mmol) was taken up in 6 mL THF and 2 mL water. To this mixture
a single crystal (<1 mg) of osmium tetroxide is added.
Once the reaction mixture turned brown, NMO (0.211g, 1.80 mmol)
was added. When the reaction was complete as determined by TLC (˜3
hours), Na2SO3 (2.3, 18 mmol) was added and
the reaction mixture was allowed to stir for hour, after which
the reaction mixture was poured into water and extracted with ethyl
acetate. The organic layer was washed with water, brine, dried over anhydrous
MgSO4 and concentrated. The crude unpurified diol was
then taken up in 25 mL CH2Cl2, and added drop wise
to a suspension of NaIO4/SiO2 (3.54
g in 50 mL in CH2Cl2). Upon consumption of
starting material as evidenced by TLC (ca 5 hours), the mixture
was filtered and concentrated. The crude unpurified dialdehyde was
then taken up in 20 mL THF and 3 drops of concentrated sulfuric acid
were added. Upon complete disappearance of starting material as
determined by TLC (ca 7 hours) solid NaHCO3 and MgSO4 were
added, and the mixture was allowed to stir for 10 minutes. The mixture
was then filtered and concentrated. Flash Column chromatography
gave compound 9a (0.345g, 1 mmol, 77%)
as an off white solid. mp 143-144 °C; 1H
NMR (400 MHz, CDCl3) δ = 9.71 (t,
J = 2.0, 1 H), 7.83 (d, J = 8.6 Hz, 1 H), 7.73 (d, J = 8.2 Hz, 2 H), 7.29 (d, J = 1.2 Hz, 1 H), 7.20 (d, J = 8.2, Hz, 2 H), 7.14 (d, J = 8.2 Hz 1 H), 4.06 (d, J = 2 Hz, 2 H), 2.36 (s, 3 H),
2.33 (s, 3 H), 2.32 (s, 3 H); 13C NMR
(100 MHz, CDCl3) 199.0, 145.0, 135.3, 134.8, 132.4, 130.6,
130.0, 127.6, 127.0, 125.0, 123.8, 118.1, 113.0, 44.6, 22.0, 20.1,
14.3; IR (thin film) = 1723, 1364, 1175 cm-1;
MS m/z (relative
intensity) 342.1 (21, M + 1), 341.1 (91, M+),
312.1 (100), 158.1 (76), 142 (24), 91 (47), 49 (26); EIHRMS for
C19H19NO3S: found 341.1089, requires
341.1086.
Direct oxidative scission was unsuccessful.