View
26
Download
9
Category
Preview:
DESCRIPTION
Nonclassical Bergman Cyclization of Enediynes : Synthesis of Dibenzofurans and Carbazoles. Chia-Ying Lee, Chi-Fong Lin, Ching-Chen Chiu, and Ming-Jung Wu* - PowerPoint PPT Presentation
Citation preview
Nonclassical Bergman Cyclization of Enediynes:Synthesis of Dibenzofurans and Carbazoles
Chia-Ying Lee, Chi-Fong Lin, Ching-Chen Chiu, and Ming-Jung Wu*Faculty of Medicinal and Applied Chemistry, and Graduate Institute of Pharmaceutical Sciences, Kaohsiung Medical University, Kaohsiung,
Taiwan
Recently, we found that treatment of 2-(6-substituted 3(Z)-henxen-1,5-diynyl)phenyl t-butyldimethylsilyl ethers 1 with sodium methoxide in refluxing methanol gave dibenzofurans 2 in excellent yield.1 The aniline analogs 3 have also been carried out to test the anionic cycloaromatization of enediynes and we found that treatment of 3 with potassium t-butoxide in NMP at 60 oC gave the carbazole 4 in 45-86 % yields.2
OTBS
R
NaOCH3
CH3OHO
R
1 2
NHAc
R
KOtBu
NMP NH
R
3 4
( Eq 1 )
( Eq 2 )
OTBS
R
X
X
10b R = C5H11 10c R = C7H15 10d R = C3H6OTHP 10e R = C4H9 10f R = C5H11 10g R = C7H15 10h R = C3H6OTHP 10i R = C4H9 10j R = C5H11
O
X
X
R
Methods
reflux, 16h
11b ( 56 % )11c ( 50 % )11d ( 57 % )11e ( 93 % )11f ( 94 % )11g ( 92 % )11h ( 91 %)11i ( 75 % )11j ( 75 % )
Method A : Na, MeOH
X,X= H, H
X,X=
X,X=
Method B : K2CO3, MeOH10b 10e
11b ( 56 % )11e ( 93 % )
Table1. Generation of 5-substituted dibenzofurans and related moleculars.
Reference:1. Wu, M. J.; Lee, J. Y.; Lin, C. F. Angew. Chem., Int. Ed. 2002, 41, 40772. Lee, C.-Y.; Lin, C.-F.; Lee, J.-L.; Chiu, C.-C.; Lu, W.-D.; Wu, M.J.; J. Org. Chem.; 2004, 69, 2106-2110
R
NH2NH
R
+
NH
R
12 13 14
Entry Yield (%)
NMP, 60 oC2 h
12b. R = C5H11 13b (47%) 14b (21%)
12c R = C6H13 13c (36%) 14c (25%)
12d. R = C7H15 13d (44%) 14d (23%)
12e. R = C3H6OTHP 13e (54%) 14e (40%)
Table 2. The results for the cyclization of compounds 12a-e using t-BuOK as a base
t-BuOK
NHCOCH3
R2
15a. R2= C3H7
15b. R2= C4H9
15c. R2= C5H11
15d. R2= C6H13
15e. R2= C7H15
15f. R2= C3H6OTHP
15g. R2=C4H8OTHP
13a. ( 86% )
13b. ( 65% )
13c. ( 77% )
13d. ( 53% )
13e. ( 60% )
13f. ( 53% )
13g. ( 45% )
KOtBu
NMP NH
R2
15 13
Entry Yields (%)
Table 4. A Hernating route for the synthesis of Carbazoles.
C4H9
H
NH2
I
C4H9
NH2
NH
C4H9
Pd ( PPh3) 4, CuI
NMP, heat
n - BuNH2 , Et2O
12 a ( 57% )
13 a( 60% )
Scheme 3. Palladium-Catalyzed Coupling of 12 and subsequent cyclization of the product 13
t-BuOK
9
14
NMP, heat
t-BuOK
NH
C4H9
13 a (58 % )
+NH
C4H9
C4H9
NHAc
15a ( 58% )
Acetyl chlorideEt3N, CH2Cl2
14 a ( 21% )
Cl
Cl
+ C4H9H
Cl
C4H9SiMe3H
C4H9
R
OTBS
IC4H9
OTBSO
C4H9
Na , MeOH
Pd ( PPh3) 4, CuI
Pd ( PPh 3 ) 4 , CuI
Pd ( PPh3) 4, CuIreflux
n - BuNH2 , Et2O
n - BuNH2 , Et2O
n - BuNH2 , Et2O
5 6 7( 51%)
8 R=TMS ( 71%)K2CO3 MeOH
9 R=H ( 86%)
10a ( 57% ) 11a( 60% )
Scheme 1. Palladium-Catalyzed Coupling of 10 and subsequent cyclization of the product11
Part A Synthesis of Dibezofuran
R
OTBS
X
Xdesilylation
R
O
X
X
O
R
O
R
H
Scheme 2 Proposed Mechanism
Part B Synthesis of Carbazole
Abstract
Recommended