65136-46-1Relevant academic research and scientific papers
Abbreviated Ibogaine Congeners. Synthesis and Reactions of Tropan-3-yl-2- and -3-indoles. Investigation of an Unusual Isomerization of 2-Substituted Indoles Using Computational and Spectroscopic Techniques
Repke, David B.,Artis, Dean R.,Nelson, Janis T.,Wong, Erik H. F.
, p. 2164 - 2171 (1994)
The syntheses of several N-methyltropan-3-ylindoles, designated as congeners of ibogaine, are described.The synthetic approach to N-methyltropan-3-yl-2-indole revealed that the tropanyl 3'-center was quite sensitive to acid-catalyzed epimerization.The carbocyclic analog, N-methyl-2--oct-3-anyl>indole, also underwent this rearrangement.However, N-methyltropan-3-yl-3-indole was insensitive to acid or base, even under more vigorous conditions.This simple isomerization is quite rare for 2-substituted indoles, especially for cases where the center of reaction is not additionally activated, and normally only takes place under extreme reaction conditions.The mechanism of this reaction was investigated using ab initio molecular orbital calculations, NMR spectroscopy, and deuterium labeling studies.These results indicate that, in contrast to those previously obtained for more reactive 2-substituted indoles, the reaction can best be explained using a simple exchange mechanism involving the exocyclic enamine tautomer of the indole ring as an intermediate.The difference in reactivity is suggested to arise from a decrease in a relative energy of the exocyclic enamine tautomer due to the presence of increased strain in the endo bicyclic 2-substituent.The title compounds displayed modest pharmacological activity in a variety of biological assays.
Facile synthesis of 2-substituted indoles and indolo[3,2-b]carbazoles from 2-(benzotriazol-1-ylmethyl)indole
Katritzky,Li,Stevens
, p. 3401 - 3404 (1995)
Replacement of the benzotriazole moiety of N-alkyl-2-(1-benzotriazol-1-ylalkyl)indoles 6 and 9, prepared from 1-propargylbenzotriazole and o-iodoaniline followed by alkylation, with Grignard reagents gave the corresponding 2-substituted indoles 10 in good
The Selective Cross-Coupling of Secondary Alkyl Zinc Reagents to Five-Membered-Ring Heterocycles Using Pd-PEPPSI-IHeptCl
Atwater, Bruce,Chandrasoma, Nalin,Mitchell, David,Rodriguez, Michael J.,Pompeo, Matthew,Froese, Robert D. J.,Organ, Michael G.
supporting information, p. 9502 - 9506 (2015/08/11)
The ability to cross-couple secondary alkyl centers is fraught with a number of problems, including difficult reductive elimination, which often leads to β-hydride elimination. Whereas catalysts have been reported that provide decent selectivity for the expected (non-rearranged) cross-coupled product with aryl or heteroaryl oxidative-addition partners, none have shown reliable selectivity with five-membered-ring heterocycles. In this report, a new, rationally designed catalyst, Pd-PEPPSI-IHeptCl, is demonstrated to be effective in selective cross-coupling reactions with secondary alkyl reagents across an impressive variety of furans, thiophenes, and benzo-fused derivatives (e.g., indoles, benzofurans), in most instances producing clean products with minimal, if any, migratory insertion for the first time. A wide variety of five-membered-ring heterocycles were successfully cross-coupled to secondary alkyl zinc reagents with the new precatalyst Pd-PEPPSI-IHeptCl, which features a bulky N-heterocyclic carbene ligand. This catalyst suppresses migratory-insertion (rearrangement) pathways, and the desired products are thus formed with high selectivity.
