916902-85-7

Upstream product

• 916902-76-6 4-tert-butyl-2-phenyloxazol-5-yl acetate 
• 4828-96-0 cis-2,3,4,4a,9,9a-hexahydro-1H-carbazole 
• 942-01-8 1,2,3,4-tetrahydrocarbazole 
• 1775-86-6 5,6,7,8,8a,9-hexahydro-4bH-carbazole 
• 444575-79-5 carbonic acid 1,1-dimethylethyl 1-phenyl-2-propenyl ester 

Downstream Products

• 1448544-30-6 C₁₈H₁₈BrNO₂S 

Relevant academic research and scientific papers

Diboron-mediated palladium-catalyzed asymmetric transfer hydrogenation using the proton of alcohols as hydrogen source

The developments of hydrogen sources stand at the forefront of asymmetric reduction. In contrast to the well-studied alcohols as hydrogen sources via β-hydride elimination, the direct utilization of the proton of alcohols as a hydrogen source for activator-mediated asymmetric reduction is rarely explored. Herein we report the proton of alcohols as a hydrogen source in diboron-mediated palladium-catalyzed asymmetric transfer hydrogenation of 1,3-diketones and indoles, providing a series of chiral β-hydroxy ketones and indolines with excellent yields and enantioselectivities. This strategy would be useful for the synthesis of chiral deuterium-labelled compounds due to the ready availability of deuterium-labelled alcohols. Mechanistic investigations and DFT calculations revealed that active chiral Pd-H species was generated from the proton of alcohols by activating of tetrahydroxydiboron, hydrogen transfer was the rate-determining step, and the reaction preferred Pd(0)-catalyzed mechanism. [Figure not available: see fulltext.]

Asymmetric Transfer Hydrogenation of N-Unprotected Indoles with Ammonia Borane

A metal-free asymmetric transfer hydrogenation of unprotected indoles was successfully realized using a catalyst derived from HB(C6F5)2 and (S)-tert-butylsulfinamide with ammonia borane as a hydrogen source. A variety of indolines were achieved in 40-78percent yields with up to 90percent ee.

Kinetic Resolution of 2-Substituted Indolines by N-Sulfonylation using an Atropisomeric 4-DMAP-N-oxide Organocatalyst

The first catalytic kinetic resolution by N-sulfonylation is described. 2-Substituted indolines are resolved (s=2.6–19) using an atropisomeric 4-dimethylaminopyridine-N-oxide (4-DMAP-N-oxide) organocatalyst. Use of 2-isopropyl-4-nitrophenylsulfonyl chloride is critical to the stereodiscrimination and enables facile deprotection of the sulfonamide products with thioglycolic acid. A qualitative model that accounts for the stereodiscrimination is proposed.

Asymmetric Hydrogenation of Unprotected Indoles Catalyzed by η6-Arene/N-Me-sulfonyldiamine-Ru(II) Complexes

Protecting-group-free transformation is a challenging and important issue in atom-economical organic synthesis. The η6-arene/N-Me-sulfonyldiamine-Ru(II)-BF4 complex-catalyzed asymmetric hydrogenation of 2-substituted unprotected indoles in weakly acidic hexafluoroisopropanol gives optically active indoline compounds with up to >99% ee. Under mild reaction media, halogen atoms and synthetically important protecting groups (e.g., silyl ether, acetal, benzyl ether, and ester) on indoles are maintained, which is advantageous for the synthesis of further complex indoline molecules.

Highly Enantioselective Synthesis of Indolines: Asymmetric Hydrogenation at Ambient Temperature and Pressure with Cationic Ruthenium Diamine Catalysts

A highly enantioselective synthesis of indolines by asymmetric hydrogenation of 1H-indoles and 3H-indoles at ambient temperature and pressure, catalyzed by chiral phosphine-free cationic ruthenium complexes, has been developed. Excellent enantio- and diastereoselectivities (up to >99 % ee, >20:1 d.r.) were obtained for a wide range of indole derivatives, including unprotected 2-substituted and 2,3-disubstituted 1H-indoles, as well as 2-alkyl- and 2-aryl-substituted 3H-indoles.

Asymmetric hydrogenation of unprotected indoles using iridium complexes derived from P-OP ligands and (reusable) Bronsted acids

Unprotected indoles have been efficiently converted to enantiomerically enriched indolines (up to 91% ee) by a stepwise process: (reusable) Bronsted acid-mediated C=C isomerisation and asymmetric hydrogenation using enantioselective iridium catalysts derived from P-OP ligands. This straightforward combination of (reusable) Bronsted acids, which activate the indole ring for hydrogenation by breaking its aromaticity, and enantiomerically pure [Ir(P-OP)]+ complexes as hydrogenation catalysts affords the resulting indolines with high enantioselectivities.

Homogenous Pd-catalyzed asymmetric hydrogenation of unprotected indoles: Scope and mechanistic studies

An efficient palladium-catalyzed asymmetric hydrogenation of a variety of unprotected indoles has been developed that gives up to 98% ee using a strong Br?nsted acid as the activator. This methodology was applied in the facile synthesis of biologically active products containing a chiral indoline skeleton. The mechanism of Pd-catalyzed asymmetric hydrogenation was investigated as well. Isotope-labeling reactions and ESI-HRMS proved that an iminium salt formed by protonation of the C=C bond of indoles was the significant intermediate in this reaction. The important proposed active catalytic Pd-H species was observed with 1H NMR spectroscopy. It was found that proton exchange between the Pd-H active species and solvent trifluoroethanol (TFE) did not occur, although this proton exchange had been previously observed between metal hydrides and alcoholic solvents. Density functional theory calculations were also carried out to give further insight into the mechanism of Pd-catalyzed asymmetric hydrogenation of indoles. This combination of experimental and theoretical studies suggests that Pd-catalyzed hydrogenation goes through a stepwise outer-sphere and ionic hydrogenation mechanism. The activation of hydrogen gas is a heterolytic process assisted by trifluoroacetate of Pd complex via a six-membered-ring transition state. The reaction proceeds well in polar solvent TFE owing to its ability to stabilize the ionic intermediates in the Pd-H generation step. The strong Br?nsted acid activator can remarkably decrease the energy barrier for both Pd-H generation and hydrogenation. The high enantioselectivity arises from a hydrogen-bonding interaction between N-H of the iminium salt and oxygen of the coordinated trifluoroacetate in the eight-membered-ring transition state for hydride transfer, while the active chiral Pd complex is a typical bifunctional catalyst, effecting both the hydrogenation and hydrogen-bonding interaction between the iminium salt and the coordinated trifluoroacetate of Pd complex. Notably, the Pd-catalyzed asymmetric hydrogenation is relatively tolerant to oxygen, acid, and water.

Chiral phosphoric acid-catalyzed oxidative kinetic resolution of indolines based on transfer hydrogenation to imines

The oxidative kinetic resolution of 2-substituted indoline derivatives was achieved by hydrogen transfer to imines by means of a chiral phosphoric acid catalyst. The oxidative kinetic resolution was applicable to racemic alkyl- or aryl-substituted indolines, and the remaining indolines were obtained in good yields with excellent enantioselectivities.

Direct asymmetric hydrosilylation of indoles: Combined Lewis base and bronsted acid activation

Quite a pair: The first organocatalytic direct asymmetric reduction of unprotected 1H-indoles to chiral indolines has been developed. The reaction proceeds through the generation of electrophilic indolenium ions by a Bronsted acid, and then chiral Lewis base (1) mediated enantioselective hydride transfer with HSiCl3. A variety of chiral indolines were obtained with moderate to excellent enantioselectivity. MOM=methoxymethyl. Copyright

Pd-catalyzed asymmetric hydrogenation of unprotected indoles activated by bronsted acids

The first highly enantioselective hydrogenation of simple indoles was developed with a Brnsted acid as an activator to form the iminium intermediate in situ, which was hydrogenated using Pd(OCOCF3)2/(R)-H8- BINAP catalyst system with up to 96% ee. The present method provides an efficient route to enantioenriched 2-substituted and 2,3-disubstituted indolines.