Diverse Strategies for the Synthesis of the Indoline Scaffold

Abstract

Because indoline is an important intermediate of angiotensin‐converting enzyme (ACE) inhibitor and the antihypertensive drug “pentopril”, and also because it is a ubiquitous scaffold found in the structures of several naturally bioactive alkaloids such as vinblastine, strychnine, (–)‐physostigmine, ajmaline, and (+)‐aspidospermidine, the synthesis of this “privileged structure” is meaningful in the design of new biologically active medicines. This microreview describes the recent advances in the synthesis of indoline derivatives, including Cu‐ and Pd‐catalyzed reactions, metal‐free approaches (radical reaction), as well as other types of reactions.

Direct Asymmetric Hydrosilylation of Indoles: Combined Lewis Base and Brønsted Acid Activation

“…[2] While a variety of protocols, including traditional enzymatic or non-enzymatic kinetic resolutions, [3] and organicmolecule-or metal-mediated asymmetric transformations [4] have been described, the direct asymmetric reduction of prochiral indole precursors would be one of the most straightforward ways to make chiral indolines.[5] Thus, a few transition metal/chiral phosphine complexes, including Rh, Ru, and Ir, have been applied by the groups of Kuwano, Feringa, Pfaltz, and others to the asymmetric hydrogenation of indoles, but the methods usually suffer from a limited substrate scope and relatively harsh reaction conditions.[6] A noteworthy breakthrough was made by Zhou, Zhang, and coworkers who reported an elegant palladium-catalyzed enantioselective hydrogenation of unprotected indoles activated by Brønsted acids. [7] In contrast, Rueping et al presented the chiral Brønsted acid catalyzed transfer hydrogenation of 3H-indoles with Hantzsch dihydropyridine as the hydrogen source.…”

“…[2] While a variety of protocols, including traditional enzymatic or non-enzymatic kinetic resolutions, [3] and organicmolecule-or metal-mediated asymmetric transformations [4] have been described, the direct asymmetric reduction of prochiral indole precursors would be one of the most straightforward ways to make chiral indolines.…”

“…[2] While a variety of protocols, including traditional enzymatic or non-enzymatic kinetic resolutions, [3] and organicmolecule-or metal-mediated asymmetric transformations [4] have been described, the direct asymmetric reduction of prochiral indole precursors would be one of the most straightforward ways to make chiral indolines. [5] Thus, a few transition metal/chiral phosphine complexes, including Rh, Ru, and Ir, have been applied by the groups of Kuwano, Feringa, Pfaltz, and others to the asymmetric hydrogenation of indoles, but the methods usually suffer from a limited substrate scope and relatively harsh reaction conditions.…”

A new scaffold of topoisomerase I inhibitors: Design, synthesis and biological evaluation

“…The interest in topoisomerase I as a therapeutic target promoted various efforts to identify other chemotypes effective as topoisomerase inhibitors and chemical/modelling efforts to rationally design specific analogs among known inhibitors [8,9,10,11] . During the last years several tetra-and pentacyclic structures containing the indoline fragment has received much attention due to the structural correlation with natural compounds belonging to the alkaloids class endowed with biological activity as cyclooxygenase/5-lipooxygenase inhibitors, characterized by the presence of the pyrrolo[3,2-de]acridine subunit [12] , indolocarbazoles non-CPT topo I inhibitors [13,14,15,16] and analogues of physostigmine alkaloids [17,18,19,20] .…”

Direct Asymmetric Hydrosilylation of Indoles: Combined Lewis Base and Brønsted Acid Activation

“…[2] While a variety of protocols, including traditional enzymatic or non-enzymatic kinetic resolutions, [3] and organicmolecule-or metal-mediated asymmetric transformations [4] have been described, the direct asymmetric reduction of prochiral indole precursors would be one of the most straightforward ways to make chiral indolines.[5] Thus, a few transition metal/chiral phosphine complexes, including Rh, Ru, and Ir, have been applied by the groups of Kuwano, Feringa, Pfaltz, and others to the asymmetric hydrogenation of indoles, but the methods usually suffer from a limited substrate scope and relatively harsh reaction conditions.[6] A noteworthy breakthrough was made by Zhou, Zhang, and coworkers who reported an elegant palladium-catalyzed enantioselective hydrogenation of unprotected indoles activated by Brønsted acids. [7] In contrast, Rueping et al presented the chiral Brønsted acid catalyzed transfer hydrogenation of 3H-indoles with Hantzsch dihydropyridine as the hydrogen source.…”