One-pot synthesis of substituted indolines via a copper-catalyzed sequential multicomponent/C-N coupling reaction

One-pot synthesis of 2-(N-sulfonylimino)indolines has been developed. The procedure combines the copper-catalyzed three-component reaction of sulfonyl azides, o-bromophenylacetylenes, and amines and the copper-catalyzed intramolecular C-N coupling in one sequence, which afforded the products in moderate to good yields. The resulting 2-(N-sulfonylimino)indolines could be easily transformed to pharmaceutically valuable oxindoles (indolin-2-ones).     

Synthesis of highly substituted indolines and indoles via intramolecular [4 + 2] cycloaddition of ynamides and conjugated enynes

Ynamides react with conjugated enynes in intramolecular [4 + 2] cycloadditions to afford substituted indolines that undergo oxidation with o-chloranil to furnish the corresponding indoles. The cycloaddition substrates are easily assembled from derivatives of 3-butynylamine by Sonogashira coupling with alkenyl halides followed by copper-catalyzed N-alkynylation with acetylenic bromides. Diynamides participate as particularly reactive 2pi components in the cycloaddition, providing access to indolines with carbon substituents at the C-7 position. Enynamides serve as 4pi components in a complementary version of the cycloaddition strategy which provides access to indoles and indolines substituted with carbon substituents at C-4. These enyne cycloadditions take place upon heating the substrates at 110-210 degrees C in toluene or 2,2,2-trifluoroethanol and in some cases can be achieved at 0 degrees C to room temperature in the presence of Lewis acids such as Me2AlCl.     

Highly efficient dehydrogenation of indolines to indoles using hydroxyapatite-bound Pd catalyst

A hydroxyapatite-bound palladium catalyst was found to be effective for the dehydrogenation of various types of indolines to give the corresponding indoles. Moreover, the catalyst was readily recovered from the reaction mixture, and could be reused without any loss of its catalytic activity.     

Easy Access to Crystalline Indolines via Hydrogen Bond Transfer

Several indoline derivatives with specific geometries are biologically active and have inhibitor properties. Many indolines are a key part of natural products. Much attention has been focused on the development of synthetic routes for their easy access. Current synthesis depends largely on metal catalysis, iodine reagents, and Oxone. To date, no synthetic route has been established that is metal‐free, reagent‐free, and environmentally friendly and provides a base for green chemistry. Here, we report the first facile metal‐free and reagent‐free synthesis of indoline derivatives, which could potentially be influential in the design of new biologically active compounds. The synthesis proceeds through intramolecular amination between a urea nucleophile and unactivated alkene. The ring closure occurs in a few hours in the presence of pre‐dried silica gel and gives good yields of indolines products, but in the absence of silica gel, the ring closure occurred overnight with stirring in dry solvent. An electron withdrawing group at the substituted aryl moiety of ureas increases the hydrogen bond donor ability of substrates that mediate the internal proton transfer at the terminal alkene and results in facile amination to give the indoline product with an “in plane” orientation of the carbonyl group and aromatic part of indoline framework. Such orientation in indolines is important for potent biological activities.     

Efficient construction of fused indolines with a 2-quaternary center via an intramolecular Heck reaction with a low catalyst loading

An efficient construction of fused indolines with a 2-quaternary center through a palladium-catalyzed intramolecular Heck reaction of N-(2(2-halobenzoxyl)-2,3-disubstituted indoles is disclosed. This protocol provided a straightforward access to diverse fused indolines with good functional group tolerance.     

Solid-phase synthesis of indolines via palladium-catalyzed cyclization

The solid-phase synthesis of indolines from resin-bound 2-bromophenylacetylated amino acids is described. The exhaustive reduction of solid-support bound amides with borane afforded the requisite secondary amines that, following the palladium-catalyzed intramolecular cyclization and cleavage, provided the corresponding disubstituted indolines.     

Cu催化吲哚啉的炔丙基烷基化/脱氢对映选择性合成手性N-炔丙基吲哚化合物(英文)

基于吲哚啉的Cu催化不对称炔丙基烷基化及DDQ脱氢策略,成功合成了手性N-炔丙基吲哚化合物.通过使用一个结构刚性的酮亚胺三齿P,N,N-配体,反应获得了很好的对映选择性.该方法反应条件温和、底物适用范围广、产物收率高、立体选择性好,为手性N-炔丙基吲哚化合物的合成提供了一条简捷、高效的新途径.     

Synthesis of 6-methoxyindoles and indolines. Regioselective c-6 bromination of indolines and subsequent nucleophilic substitution with a methoxyl group

Regioselective bromination of the 6-position of indolines was investigated. Treatment of indolines with bromine in sulfuric acid in the presence of silver sulfate or with bromine in superacid afforded the 6-bromoindolines, which were converted to 6-methoxyindolines and indoles.     

Chiral Phosphoric Acid Catalyzed Kinetic Resolution of Indolines Based on a Self‐Redox Reaction

A strategy for oxidative kinetic resolution of racemic indolines was developed, employing salicylaldehyde derivative as the pre‐resolving reagent and chiral phosphoric acid as the catalyst. The iminium intermediate, formed by the condensation reaction of an enantiomer of indoline with salicylaldehyde derivative, was hydrogenated by the same enantiomer of indoline to afford another enantiomer of indoline by a self‐redox mechanism. The oxidative kinetic resolution of 2‐aryl‐substituted indolines proceeded to give enantiomers in good yields with excellent enantioselectivities.     

Asymmetric synthesis of trans-2,3-disubstituted indoline derivatives

A novel method for asymmetric synthesis of trans-2,3-disubstituted indolines has been developed. The strategy involves the (-)-sparteine-mediated electrophilic substitution of 2-benzyl N-pivaloylaniline with aromatic or α,β-unsaturated aldehydes and subsequent intramolecular nucleophilic substitution. The simple protocol for two-step process can produce highly enantioenriched indolines 3a-o up to 98:2 er.     

Gold‐Catalyzed Cascade Cyclization of 2‐Alkynyl‐N‐Propargylanilines by Rearrangement of a Propargyl Group

Gold catalysis enables direct construction of tetracyclic fused indolines through the migration of a propargyl substituent from an aniline nitrogen atom to the C3‐position of an indole from 2‐alkynyl‐N‐propargylanilines. This reaction provides rapid access to fused three‐dimensional indolines in a single operation with the formation of four bonds and three rings.     

Introduction of a methoxyl group into indoles and 2,3-dihydroindoles. A new synthesis of 5-hydroxytryptamine (serotonin)

Methoxylation of the 5-position of indoles and indolines was investigated. Treatment of 5-bromo-iodoles and indolines with cuprous iodide and sodium methoxide in methanol/dimethylformamide afforded the corresponding methoxy compounds. This methoxylation reaction was applied to the new synthesis of serotonin.     

One-pot cyclization of 2-aminophenethyl alcohols: a novel and direct approach to the synthesis of N-acyl indolines

A unique one-pot cyclization of 2-aminophenethyl alcohols with carboxylic acids in the presence of PPh3, CCl4, and NEt3 furnished the formation of N-acyl indolines in good to excellent yields. This new approach provides an efficient, scalable, low-cost, and direct access to the biologically important indolines which are further oxidizable to indoles and oxindoles.     

Enantioselective synthesis of 2-methyl indolines by palladium catalysed asymmetric C(sp3)-H activation/cyclisation

The first example of the enantioselective methyl C-H activation by an intramolecular ArPdX species and subsequent cyclisation was developed. Palladium catalysts using commercially available chiral diphosphines yield good ee's (up to 93% ee) in the synthesis of 2-methyl indolines from 2-halo N-isopropyl anilides. This approach was also employed for the synthesis of enantioenriched cyclohexyl fused indolines with moderate enantioselectivities.     

Recent advances in asymmetric synthesis of 2-substituted indoline derivatives

Recent advances in asymmetric synthesis of 2-substituted indoline derivatives are discussed.     

Strategies for the synthesis of 2-substituted indoles and indolines starting from acyclic alpha-phosphoryloxy enecarbamates

Strategies have been developed for the synthesis of 2-substituted indoles and indolines starting from acyclic alpha-phosphoryloxy enecarbamates. A highly chemoselective cross-coupling of N-(o-bromophenyl)-alpha-phosphoryloxyenecarbamates with boron nucleophiles enabled the efficient preparation of various N-(o-bromophenyl)enecarbamates, which served as useful precursors for subsequent Heck-type cyclization or 5-endo-trig aryl radical cyclization to furnish 2-substituted indoles or indolines, respectively.     

Rhodium-catalyzed oxidative homologation of N-pyrimidyl indolines with alkynes via dual C—H activation: Facile synthesis of benzo[g] indolines

An efficient route to benzo[g]indolines by a rhodium-catalyzed C6- and C7 H functionalization of indolines with alkynes was achieved, which is potentially applicable to the synthesis of benzo[g] indoles through oxidation/removal of the directing group.     

Electrochemical synthesis of 3-azido-indolines from amino-azidation of alkenes

An electrochemical amino-azidation of 2-aminostyre ne with sodium azide(NaN_3) was developed,which can be carried out smoothly in water under metal-free condition,affording a series of 3-azido indolines with high yields.     

Synthesis of Indolines and Derivatives by Aza‐Heck Cyclization

For the first time, an aza‐Heck cyclization that allows the preparation of indoline scaffolds is described. Using N‐hydroxy anilines as electrophiles, which can be easily accessed from the corresponding nitroarenes, this method provides indolines bearing pendant functionality and complex ring topologies. Synthesis of challenging indolines, such as those bearing fully substituted carbon atoms at C2, is also possible using this method.     

A facile synthesis of N,3-disubstituted indoles and 3-hydroxyl indolines via an intramolecular SNAr of fluorinated amino alcohols

In this Letter, we describe a practical and highly versatile method for the preparation of N,3-disubstituted indoles and 3-hydroxyl indolines. This synthetic strategy relies on an epoxide-opening followed by an intramolecular S_NAr of the resulting fluoroaryl amino alcohols. The reaction afforded 3-hydroxyl indolines when carried out at lower temperature for the derivatives bearing multi-fluorine substituents at the aromatic ring.