Books
in black and white
Main menu
Home About us Share a book
Books
Biology Business Chemistry Computers Culture Economics Fiction Games Guide History Management Mathematical Medicine Mental Fitnes Physics Psychology Scince Sport Technics
Ads

Indoles - Sundberg R.J.

Sundberg R.J. Indoles - Academic press, 1996. - 95 p.
ISBN 0-12-676945-1
Download (direct link): indoles1996.djvu
Previous << 1 .. 14 15 16 17 18 19 < 20 > 21 22 23 24 25 26 .. 68 >> Next

ГМ
гч
2 & ^ с — х 5>Q J2 “4S
е
<N еч
>,

£
Я
— >л
>% xJ
С 'С
<2 >> 3 ?■
СЛ тд-
и •
g §2
S®-5' ■1 Ё S
П ЧЭ
2.4 1NDOLHS FROM o-AMINO- OR o-NI'l ROPHFNYLACFTYLF.NFS
23
done using PdCl2 in acetonitrile. This sequence was subsequently converted to a one-pot process by use of PdCl2-mediated coupling/cychVation in a two-phase system consisting of CH2C12 and aq. n-Bu4N+Br~[8]. These conditions promote protonolysis of the indol-3-ylpalladium intermediate formed in the cyclization.
r',c oso2cf3 iC
+ Jy, Pd(PPh3>; fV
NH2 Cu1, Et2NH ^^nh2
PdCI2
(2.14)
Tandem cyclization/3-substitution can be achieved starting with o-(trifluoro-acetamido)phenylacetylenes. Cyclization and coupling with cycloalkenyl trif-lates can be done with Pd(PPh3)4 as the catalyst[9]. The Pd presumably cycles between the (0) and (II) oxidation levels by oxidative addition with the triflate and the reductive elimination which completes the 3-alkenylation. The N-protecting group is removed by solvolysis under the reaction conditions. 3-Aryl groups can also be introduced using aryl iodides[9].
Pd(ii)
NHCCF3
о
(2.15)
Tandem cyclization and 3-carboxylation has been done with o-(methanesulf-onamido)phenylacetylenes by conducting the reaction in methanol under a CO atmosphere[10],
,CPh СОгСНз
C CO, MeOH ,, „
ph (2.16)
NH
PdCI2, CuCI2
24
2 CATEGORY I a CYCLIZATIONS
Procedures
1 -Acetyl-2-butyl-5-chloroindole[1 ]
A mixture of 2-bromo-4-chloroacetanilide (1.038 g, 4.36 mmol), tri(-n-butyl)-hexynylstannane (1.86 g, 5.01 mmol) and Pd(PPh3)4 (0.151 g, 0.131 mmol) in toluene (40 ml) was heated at 100°C for 1.5 h. The solvent was removed in vacuo and the residue eluted through silica gel with 4:1 hexane-EtOAc to give 2-(l-hexynyl)-4-chloroaeetanilide (0.881 g) in 81% yield. To a solution of
2-(l-hexynyl)-4-chloroacetanilide(0.115 g, 0.46mmol) in acetonitrile (6 ml) was added PdCl2(CH3CN)2 (12 mg, 10 mol%). The mixture was heated at 80°C for
2 h. The solvent was removed in vacuo and the residue eluted through silica gel with 5:1 hexane-EtOAc to yield 95 mg (83% yield) of the product.
2-(3-i-Acetoxyandrost-16-en-17-yl)indole[8]
A solution of 3-a-acetoxyandrost-16-en-17-yl triflate (0.230 g, 0.49 mmol) in DMF (0.5 ml) and Et2NH (2 ml) was prepared and, with stirring, 2-ethynylani-line (0.058 g, 0.49 mmol), Pd(PPh3)4 (11 mg, 2mol%) and Cul (4 mg, 4mol%) were added. The reaction mixture was stirred for 6h at room temperature under a nitrogen atmosphere and then concentrated in vacuo with gentle warming. The residue was dissolved in CH2C12 (13 ml) and 0.5 N HC1 (5 ml), PdCl2 (5 mg, 6mol%) and Bu4N + C1~ (15 mg, 10mol%) were added. The mixture was stirred at room temperature for 48 h under nitrogen. The solvents were removed in vacuo and the residue purified by chromatography on silica gel using 4:1 hexane-EtOAc for elution to give the product (0.205 g) in 96% overall yield.
References
1. D. E. Rudisill and J, K. Stille, J. Org. Chem. 54, 5856 (1989).
2. T. Sakamoto. Y. Kondo, S. iwashita, T. Nagano and H. Yamanaka, Chem. Pharm. Bull. 36, 1305 (1988).
3. С. E. Castro, E. J. Gaughan and D. C. Owsley, J. Org. Chem. 31, 4071 (1966).
4. R. C. Larock and L. W. Harrison, J. Am. Chem. Soc. 106, 4218 (1984).
5. R. D. Stephens and С. E. Castro, J. Org. Chem. 28, 3313 (1963).
6. V. Kumar, J. A. Dority, E. R. Bacon, B. Singh and G. Y. Lesher, J. Org. Chem. 57, 6995 (1992).
7. A. Arcadi. S. Cacchi and F. Marinelli, Tetrahedron Lett., 30, 2581 (1989).
8. S. Cacchi, V. Camicelli and F. Marinelli, J. Organomet. Chem. 475, 289 (1994).
9. A. Arcadi, S. Cacchi and F. Marinelli, Tetrahedron Leti. 33, 3915 (1992)
10. Y. Kondo, F. Shiga, N. Murata, T. Sakamoto and H. Yamanaka, Tetrahedron 50, 11 803 (1994).
2.5 REDUCTIVE CYCLIZATION OF o-NITROSTYRENES
Several procedures have been explored for the reductive cyclization of o-nitrostyrenes. Triethyl phosphite accomplishes this transformation by ‘deoxy-
2.5 REDUCTIVE CYCLIZATION OF o-NITROSTYRENES
25
Table 2.4
Indoles by reductive cyclization of o-nitrostyrenes
Entry Substituents Reagents Yield (%) Ref.
1 2-(Methoxycarbonyl) Pd(PPh3),Cl„ CO, SnCl2 60 m
2 2-Propyl P(OC2H5)3, 160°C 60 ГП
3 2-(2-Pyridyl) P(OC2H,)3, 160°C 65 Г91
4 2-(2-Pyridyl) Ru3(CO),2. CO 63 ГЮ1
5 2-[2-( 3-Methylpyrid-2-yl)-dioxolan-2-yl P(OC2H5)3, 160° С 52 [ii]
6 2-(5,6-Dimethoxyindol-2-yl)- 3-phenylthio P(OC2H5)3, 160°C >90 [12]
7 2-(Ethoxycarbonyl)-5,6- methylendioxy P(OC2H5)3, 160°C 86 [7]
8 Furo[3,2-b] P(OC2H5)3, 160’C 34 [13]
gcnation’[l,2]. More recently, a PdCl2-PPh3-SnCl2 system has been found to effect cyclization using CO as the reductant[3], There are several potential routes to o-nitrostyrenes, including Horner-Emmons-Wittig condensation with diethyl onitrobenzylphosphonate[l]. While these reductive cyclizations can formally be considered to be ‘nitrenoid’ in charactcr, various observations suggest this to be an oversimplification[1,3]. It seems more likely that each of the reductants generates a specific electrophilic nitrogen intermediate which attacks the adjacent double bond. The structure of the reactive intermediate may vary with the reductant. An interesting feature of the phosphite deoxygenation method is that it can be applied to (3,13-disubstituted o-nitro-styrenes, in which case one of the (3-substituents migrates to become the indole
Previous << 1 .. 14 15 16 17 18 19 < 20 > 21 22 23 24 25 26 .. 68 >> Next