Stereoconvergent,Redox‐Neutral Access to Tetrahydroquinoxalines through Relay Epoxide Opening/Amination of Alcohols

We present an economical catalytic procedure to convert readily available 1,2‐diaminobenzenes and terminal epoxides into valuable 1,2,3,4‐tetrahydroquinoxalines in a highly enantioselective fashion. This procedure operates through relay zinc and iridium catalysis, and achieves redox‐neutral and stereoconvergent production of valuable chiral heterocycles from racemic starting materials with water as the only side product. The use of commercially available reagents and catalysts and a convenient procedure also make this catalytic method attractive for practical application.     

Stereoconvergent,Redox‐Neutral Access to Tetrahydroquinoxalines through Relay Epoxide Opening/Amination of Alcohols

We present an economical catalytic procedure to convert readily available 1,2‐diaminobenzenes and terminal epoxides into valuable 1,2,3,4‐tetrahydroquinoxalines in a highly enantioselective fashion. This procedure operates through relay zinc and iridium catalysis, and achieves redox‐neutral and stereoconvergent production of valuable chiral heterocycles from racemic starting materials with water as the only side product. The use of commercially available reagents and catalysts and a convenient procedure also make this catalytic method attractive for practical application.     

Atropoenantioselective Redox‐Neutral Amination of Biaryl Compounds through Borrowing Hydrogen and Dynamic Kinetic Resolution

We report herein a novel atropoenantioselective redox‐neutral amination of biaryl compounds triggered by a cascade of borrowing hydrogen and dynamic kinetic resolution under the cooperative catalysis of a chiral iridium complex and an achiral Brønsted acid. This protocol features broad substrate scope and good functional‐group tolerance, and allows the rapid assembly of axially chiral biaryl compounds in good to high yields and with high to excellent enantioselectivity.     

Catalytic Enantioselective Amination of Alcohols by the Use of Borrowing Hydrogen Methodology: Cooperative Catalysis by Iridium and a Chiral Phosphoric Acid

The catalytic asymmetric reduction of ketimines has been explored extensively for the synthesis of chiral amines, with reductants ranging from Hantzsch esters, silanes, and formic acid to H₂ gas. Alternatively, the amination of alcohols by the use of borrowing hydrogen methodology has proven a highly atom economical and green method for the production of amines without an external reductant, as the alcohol substrate serves as the H₂ donor. A catalytic enantioselective variant of this process for the synthesis of chiral amines, however, was not known. We have examined various transition‐metal complexes supported by chiral ligands known for asymmetric hydrogenation reactions, in combination with chiral Brønsted acids, which proved essential for the formation of the imine intermediate and the transfer‐hydrogenation step. Our studies led to an asymmetric amination of alcohols to provide access to a wide range of chiral amines with good to excellent enantioselectivity.     

γ‐Functionalizations of Amines through Visible‐Light‐Mediated,Redox‐Neutral C−C Bond Cleavage

Cleavage of unstrained C−C bonds under mild, redox‐neutral conditions represents a challenging endeavor which is accomplished here in the context of a flexible, visible‐light‐mediated, γ‐functionalization of amines. In situ generated C‐centered radicals are harvested in the presence of Michael acceptors, thiols and alkyl halides to efficiently form new C(sp³)−C(sp³), C(sp³)−H and C(sp³)−Br bonds, respectively.     

Synergistic Relay Reactions To Achieve Redox‐Neutral α‐Alkylations of Olefinic Alcohols with Ruthenium(II) Catalysis

Herein, we report a ruthenium‐catalyzed redox‐neutral α‐alkylation of unsaturated alcohols based on a synergistic relay process involving olefin isomerization (chain walking) and umpolung hydrazone addition, which takes advantage of the interaction between the two rather inefficient individual reaction steps to enable an efficient overall process. This transformation shows the compatibility of hydrazone‐type “carbanions” and active protons in a one‐pot reaction, and at the same time achieves the first Grignard‐type nucleophilic addition using olefinic alcohols as latent carbonyl groups, providing a higher yield of the corresponding secondary alcohol than the classical hydrazone addition to aldehydes does. A broad scope of unsaturated alcohols and hydrazones, including some complex structures, can be successfully employed in this reaction, which shows the versatility of this approach and its suitability as an alternative, efficient means for the generation of secondary and tertiary alcohols.     

Highly Regio‐ and Stereodivergent Access to 1,2‐Amino Alcohols or 1,4‐Fluoro Alcohols by NHC‐Catalyzed Ring Opening of Epoxy enals

Described is an unprecedented NHC‐catalyzed (NHC=N‐heterocyclic carbene), stereoselective ring opening of epoxy and cyclopropyl enals to deliver valuable compounds bearing multiple stereocenters. A straightforward three‐step procedure involving two catalytic enantioselective transformations has been developed and leads to a regio‐ and stereodivergent synthesis of either 1,2‐amino alcohols/diamines or 1,4‐fluoro alcohols with excellent diastereo‐ and enantiopurity.     

Cobalt(III)‐Catalyzed Redox‐Neutral Synthesis of Unprotected Indoles Featuring an N−N Bond Cleavage

A redox‐neutral cobalt(III)‐catalyzed synthetic approach for the direct synthesis of unprotected indoles showcasing an N?N bond cleavage is reported. The herein newly introduced Boc‐protected hydrazines establish a beneficial addition to the limited portfolio of oxidizing directing groups for cobalt(III) catalysis. Moreover, the developed catalytic methodology tolerates a good variety of functional groups.     

Manganese(I)‐Catalyzed β‐Methylation of Alcohols Using Methanol as C1 Source

Highly selective β‐methylation of alcohols was achieved using an earth‐abundant first row transition metal in the air stable molecular manganese complex [Mn(CO)₂Br[HN(C₂H₄PⁱPr₂)₂]] 1 ([HN(C₂H₄PⁱPr₂)₂]=MACHO‐ⁱPr). The reaction requires only low loadings of 1 (0.5 mol %), methanolate as base and MeOH as methylation reagent as well as solvent. Various alcohols were β‐methylated with very good selectivity (>99 %) and excellent yield (up to 94 %). Biomass derived aliphatic alcohols and diols were also selectively methylated on the β‐position, opening a pathway to “biohybrid” molecules constructed entirely from non‐fossil carbon. Mechanistic studies indicate that the reaction proceeds through a borrowing hydrogen pathway involving metal–ligand cooperation at the Mn‐pincer complex. This transformation provides a convenient, economical, and environmentally benign pathway for the selective C?C bond formation with potential applications for the preparation of advanced biofuels, fine chemicals, and biologically active molecules     

Iron‐Catalyzed α‐Alkylation of Ketones with Alcohols

A general and benign iron‐catalyzed α‐alkylation reaction of ketones with primary alcohols has been developed. The key to success of the reaction is the use of a Knölker‐type complex as catalyst (2 mol %) in the presence of Cs₂CO₃ as base (10 mol %) under hydrogen‐borrowing conditions. Using 2‐aminobenzyl alcohol as alkylation reagent allows for the “green” synthesis of quinoline derivatives.     

Regio‐ and Enantioselective Synthesis of N‐Allylindoles by Iridium‐Catalyzed Allylic Amination/Transition‐Metal‐Catalyzed Cyclization Reactions

Regio‐ and enantioselective synthesis of N‐allylindoles was realized through an iridium‐catalyzed asymmetric allylic amination reaction with 2‐alkynylanilines and subsequent transition‐metal‐catalyzed cyclization reactions. The highly enantioenriched allylic amines prepared from Ir‐catalysis were treated with catalytic amount of NaAuCl₄ ? 2 H₂O or PdCl₂ providing various substituted N‐allylindoles in excellent yields and enantioselectivities.     

Asymmetric Ruthenium‐Catalyzed Hydrogenation of 2,6‐Disubstituted 1,5‐Naphthyridines: Access to Chiral 1,5‐Diaza‐cis‐Decalins

The first asymmetric hydrogenation (AH) of 2,6‐disubstituted and 2,3,6‐trisubstituted 1,5‐naphthyridines, catalyzed by chiral cationic ruthenium diamine complexes, has been developed. A wide range of 1,5‐naphthyridine derivatives were efficiently hydrogenated to give 1,2,3,4‐tetrahydro‐1,5‐naphthyridines with up to 99 % ee and full conversions. This facile and green protocol is applicable to the scaled‐up synthesis of optically pure 1,5‐diaza‐cis‐decalins, which have been used as rigid chelating diamine ligands for asymmetric synthesis.