trans-endo-Decahydroquinolin-4-one DeriVatiVes
SCHEME 1. The Conformations of Compounds 4, 5, 6, and 7a
a The conformation of products 4-7 was deduced from the values of the half bandwidth of H-9 and H-10 protons or their coupling constants.
SCHEME 2. The Three-Component Synthesis of
Hydrodecaquinolinone Derivative
In preliminary experiments with different amounts of iodine,
first, reaction of 1, 2, and 3 in the presence 0.2 equiv of iodine
for 48 h afford trans-endo-N-phenyl-2-phenyldecahydroquinolin-
4-one (4) in 52%, with 40% of benzaldehyde (1) recovered
(entry 1). Surprisingly, increasing the amount of iodine (0.5
equiv) improved the results dramatically giving 76% of 4 (entry
2). Similarly, the reaction proceeded rapidly with good yield
(75%) when the amount of iodine was increased to 1.0 equiv
for 4 h under similar conditions (entry 3). However, the yields
decreased to 59% when the reaction was performed in the
presence of an excess amount (1.5 equiv) of iodine for 18 h
(entry 4). A possible explanation for the decrease in product
yields (4) is that part of iodine could have reacted with aniline
to give 4-iodoaniline.6 On the basis of the conditions of entry
4, we also found the optimal amount of aniline (2) and
1-acetylcyclohexene (3) to be 1.2 and 2.0 equiv, respectively
(entries 5-7). Solvent also has a significant impact on the
reaction efficiency and yields (entries 8-13). Ethyl ether is
commonly used when iodine is employed as a Lewis acid;
however, in certain cases it can be replaced by ethyl acetate
(EA) or other solvents. DMSO, CH2Cl2, CH3OH, and CHCl3
were screened as solvents but unsatisfactory yields and/or long
reaction times were observed in the one-pot system (entries
8-12). However, the use of ethyl ether led to excellent yields
of the three-component reaction products (entries 13 and 14).
After a series of optimization experiments, ethyl ether was found
to be the best solvent and the yield of 4 reached 99%
(diastereoselectivity >20:1) when 1.0 equiv of benzaldehyde
(1) was reacted with 2.0 equiv of aniline (2), 1.5 equiv of 3,
and 1.0 equiv of iodine in ethyl ether at room temperature for
2 h (entry 14). By the way, the stereochemistry and conforma-
tion of product 4 has been confirmed by Wartski and Seyden-
Penne already.4a Under thermodynamic control, product 4 is
highly favored and the conformations of trans-endo-N-phenyl-
2-aryldecahydroquinolin-4-one derivatives (4) were determined
by single-crystal X-ray diffraction studies of 4, 8, 9, and 15
(see Figure 1 and Supporting Information).
neat or high-concentration conditions to afford trans-N-phenyl-
2-aryldecahydroquinolin-4-one in excellent yields and diaste-
reoselectivities.
Result and Discussion
For the one-pot preparation of trans-endo-N-phenyl-2-phe-
nyldecahydroquinolin-4-one (4), initial experiments were carried
out with benzaldehyde (1) (R1 ) C6H5), aniline (2) (R2 ) C6H5),
and 1-acetylcyclohexene (3) in the presence of iodine at room
temperature. Optimization of the ratios of 1, 2, 3, and iodine
ultimately afforded reasonable yields of trans-endo-N-phenyl-
2-phenyldecahydroquinolin-4-one (4) (Table 1, entries 1-7).
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In Table 2, the reaction of aryl aldehyde (1) (1.0 equiv),
aniline (2) (1.5 equiv), and 1-acetylcyclohexene (3) (2.0 equiv)
in the presence of iodine (1.0 equiv) in 0.5 mL of ethyl ether at
room temperature gave trans-endo-N-phenyl-2-aryldecahydro-
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J. Org. Chem, Vol. 71, No. 17, 2006 6589