synthesis and catalytic functionalization of biologically active indoles

More documents

Recommendations

Info

1 Palladium-catalyzed Coupling Reactions of Indoles 21 considerable less reactive. They gave generally lower yields of biaryls, especially in couplings involving unprotected indoles. 5 6 4 2 7 R2 Br 5 6 (HO) 2B 5 Br 7 N R 1 N R 1 N R 1 4 2 R2 6 4 2 7 R2 5 6 7 O B O N R 1 4 2 R 2 B(OH) 2 Br O B O Br Pd(PPh 3) 4, Na 2CO 3 PhMe/EtOH/H 2O Pd(PPh 3) 4, Na 2CO 3 PhMe/EtOH/H 2O PdCl 2(dppf), K 3PO 4 1,4-dioxane PdCl 2(dppf), K 3PO 4 1,4-dioxane Scheme 14. Suzuki-coupling reaction of different indole boronic acids and -esters. Only traces of the desired biaryl product were found. Another role played the assignment of the partner. Reactions employing arylboronic acids gave different results when partner roles were swapped. The formation of the biaryl proceeded most efficiently when the heterocycle was the bromoaryl partner. When indolyl boronic acids were coupled with phenylbromides, yield was generally lower. In the case of the arylpinacolboronates the partner role swapping had a limited impact. Similar results were obtained whether the heterocycle was the aryl bromide or the arylboronate ester. The last influence was whether the indole was protected or not. In couplings between phenylbromides and indolyl boronic acids, the influence of the substituent at nitrogen was unimportant. However, it was substantial in couplings between phenyl bromides and indolyl boronic acids where the yields diminished as the electron-withdrawing capacity of the substituent increased. Suzuki couplings employing either phenyl or indole-derived arylpinacolboronate esters gave only traces of biaryl with unprotected indoles. Only the strongly electron-withdrawing Tos-group gave acceptable yields. To ensure optimum 5 6 7 R 2 N R 1
1 Palladium-catalyzed Coupling Reactions of Indoles 22 results in Suzuki coupling reactions it seems clear that careful selection of protecting groups and of the arylboron reagent together with a judicious assignment of the component roles are crucial. A highly efficient Suzuki-Miyaura coupling reaction of �-chloroalkylidene-�- lactones and �-lactams with organoboronic acids was developed by a Hou et al.. [65] �-Lactones [66] and �-lactams [67] are structural units in biologically active natural products. Different boronic acids were coupled with (Z)-�-chloroalkylidene-�- lactones 63 and 66 to gave products in excellent yields. It was observed that electron-withdrawing groups on the phenyl ring of aromatic boronic acids were more efficient than those bearing a electron-donating group. [68] 2-Indolyl-groups were easily introduced via coupling protocol (Scheme 15). Different effects of base and solvents in these Suzuki-Miyaura reactions were tested but did not mention here. Scheme 15 just shows the coupling reactions with indol-2-yl boronic acid 64 to the corresponding indole lacton products 65 (63%) and 67 (62%) in good yield, in the presence of catalst D, K3PO4·3H2O as base in toluene under reflux. The catalyst D was prepared in advance by stirring 2 equiv of Sphos with PdCl2(PhCN)2 in benzene for 1 day at room temperature. [32a,69] Cl Cl Ph O Cy O N Boc B(OH) 2 catalyst D (5 mol%) . K3PO4 3 H2O (2 equiv) toluene, reflux, 180 min OMe Ph NBoc O 63 64 65 (63%) Cy2P Cl Pd Cy2P MeO Cl MeO O O Et N Boc B(OH) 2 OMe catalyst D catalyst D (5 mol%) K 3PO 4 . 3 H2O (2 equiv) toluene, reflux, 180 min NBoc 66 64 67 (62%) Scheme 15. Palladium-catalyzed Suzuki-Miyaura reaction with lacton derivatives. O O O Cy Et
Page 1 and 2: Leibniz-Institut für Katalyse e. V
Page 3 and 4: Für meine Eltern Siegfried und Ker
Page 5 and 6: Mein besonderer Dank gilt Dr. Anneg
Page 7 and 8: Table of Contents Preface .........
Page 9 and 10: List of Abbreviations Ac Acetyl aq
Page 11 and 12: Preface The search for drugs is an
Page 13 and 14: 1 Palladium-catalyzed Coupling Reac
Page 31: 1 Palladium-catalyzed Coupling Reac
Page 83 and 84:
1 Palladium-catalyzed Coupling Reac
Page 85 and 86:
Page 87 and 88:
Page 89 and 90:
3 Publications 3.1 Titanium-Catalyz
Page 91 and 92:
1092 N. Schwarz et al. LETTER Table
Page 93 and 94:
1094 N. Schwarz et al. LETTER 2,6-d
Page 95 and 96:
3 Publications 84 3.2 Zinc-Promoted
Page 97 and 98:
Table 2: Reaction of N-methyl-N-phe
Page 99 and 100:
Am. Chem. Soc. 2002, 124, 15168 - 1
Page 101 and 102:
A novel palladium catalyst for the
Page 103 and 104:
Table 2. Reaction of different amin
Page 105 and 106:
3 Publications 94 Experimental Data
Page 107 and 108:
3 Publications 96 (q); 115.3 (d, J
Page 109 and 110:
3 Publications 98 3.4 Palladium-Cat
Page 111 and 112:
PAPER Coupling Reactions of Electro
Page 113 and 114:
Page 115 and 116:
Page 117 and 118:
Page 119 and 120:
3 Publications 108 3.5 Synthesis of
Page 121 and 122:
Scheme 2 Ti-catalyzed synthesis of
Page 123 and 124:
mixture was used for the synthesis
Page 125 and 126:
7.11 (ddd, 1H, J = 8.0 Hz, J = 7.0
Page 127 and 128:
FULL PAPER DOI: 10.1002/ejoc.200800
Page 129 and 130:
Synthesis of Potential 5-HT 6 Recep
Page 131 and 132:
Page 133 and 134:
Page 135 and 136:
Page 137 and 138:
Page 139 and 140:
FULL PAPER DOI: 10.1002/ejoc.200700
Page 141 and 142:
Synthesis of Indole-2,3-dicarboxyla
Page 143 and 144:
3 Publications 132 3.8 Selective Re
Page 145 and 146:
8 7 N R N R OH CO2Et CO2Et OH indol
Page 147 and 148:
mixture was stirred at 78 C for 3 m
Page 149 and 150:
3.89 (s, 2H, H-10), 4.27 (s, 2H, H-
Page 151 and 152:
DOI: 10.1002/cssc.200700160 General
Page 153 and 154:
Zn-Catalyzed Hydroamination of Term
Page 155 and 156:
Zn-Catalyzed Hydroamination of Term
Page 157 and 158:
3 Publications 146 3.10 Zn-Catalyze
Page 159 and 160:
Over the past years, we investigate
Page 161 and 162:
3 Publications 150 3.11 First Synth
Page 163 and 164:
4608 K. Alex et al. / Tetrahedron L
Page 165 and 166:
Publikationen 1 Titanium-Catalyzed
show all

synthesis and catalytic functionalization of biologically active indoles

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?