Tackling N‐Alkyl Imines with 3d Metal Catalysis: Highly Enantioselective Iron‐Catalyzed Synthesis of α‐Chiral Amines

A readily activated iron alkyl precatalyst effectively catalyzes the highly enantioselective hydroboration of N‐alkyl imines. Employing a chiral bis(oxazolinylmethylidene)isoindoline pincer ligand, the asymmetric reduction of various acyclic N‐alkyl imines provided the corresponding α‐chiral amines in excellent yields and with up to >99 % ee. The applicability of this base metal catalytic system was further demonstrated with the synthesis of the pharmaceuticals Fendiline and Tecalcet.     

Highly Enantioselective Aza‐Michael Reaction between Alkyl Amines and β‐Trifluoromethyl β‐Aryl Nitroolefins

The aza‐Michael addition reaction is a vital transformation for the synthesis of functionalized chiral amines. Despite intensive research, enantioselective aza‐Michael reactions with alkyl amines as the nitrogen donor have not been successful. We report the use of chiral N‐heterocyclic carbenes (NHCs) as noncovalent organocatalysts to promote a highly selective aza‐Michael reaction between primary alkyl amines and β‐trifluoromethyl β‐aryl nitroolefins. In contrast to classical conjugate‐addition reactions, a strategy of HOMO‐raising activation was used. Chiral trifluoromethylated amines were synthesized in high yield (up to 99 %) with excellent enantioselectivity (up to 98 % ee).     

Enantioselective NH Insertion Reaction of α‐Aryl α‐Diazoketones: An Efficient Route to Chiral α‐Aminoketones

A highly enantioselective N? H insertion reaction of α‐diazoketones was developed by using cooperative catalysis by dirhodium(II) carboxylates and chiral spiro phosphoric acids. The insertion reaction provides a new access route to diverse chiral α‐aminoketones, which are versatile building blocks in organic synthesis, with fast reaction rates, good yields and high enantioselectivity under mild and neutral conditions.     

Regioselective and Enantioselective Synthesis of β‐Indolyl Cyclopentenamides by Chiral Anion Catalysis

The regioselective and enantioselective synthesis of β‐indolyl cyclopentenamides, a versatile chiral building block, by asymmetric addition of indoles to α,β‐unsaturated iminium intermediates has been achieved through chiral anion catalysis. Key to the success of this methodology is the generation of a chiral anion‐paired ketone‐type α,β‐unsaturated iminium intermediate from α‐hydroxy enamides. Preliminary mechanistic studies and DFT calculations are consistent with a mechanism involving multiple, concurrent pathways for isomerization of the initially formed azaallylcation into the key α,β‐unsaturated iminium intermediate, all mediated by the phosphoric acid catalyst.     

Highly Enantioselective [3+2] Cycloaddition of Vinylcyclopropane with Nitroalkenes Catalyzed by Palladium(0) with a Chiral Bis(tert‐amine) Ligand

An enantioselective [3+2] cycloaddition of vinyl cyclopropane derived from 1,3‐indanedione with nitroalkenes catalyzed by palladium(0) with a chiral bis(tert‐amine) ligand was developed in high yields with good diastereoselectivities and excellent enantioselectivities. The resulting bis(tert‐amine)–palladium complex proved to be a highly efficient catalyst for this cycloaddition.     

Dual Catalysis with Copper and Rhenium for Trifluoromethylation of Propargylic Alcohols: Efficient Synthesis of α‐Trifluoromethylated Enones

Trifluoromethylation of propargylic alcohols to provide (Z)‐α‐trifluoromethylated enones and β‐unsubstituted α‐trifluoromethylated enones proceeded with high yield and selectivity in the presence of CuI/Re₂O₇. The Z isomer was formed under kinetic control, though it is less stable than the E isomer in terms of steric repulsion.     

Synthesis of Chiral Exocyclic Amines by Asymmetric Hydrogenation of Aromatic Quinolin‐3‐amines

Asymmetric hydrogenation of aromatic quinolin‐3‐amines was successfully developed with up to 94 % enantiomeric excess (ee). Introduction of the phthaloyl moiety to the amino group is crucial to eliminate the inhibition effect caused by the substrate and product, to activate the aromatic ring, and to improve the diastereoselectivity. This new methodology provides direct and facile access to chiral exocyclic amines. Notably, this report is the first on the highly enantioselective hydrogenation of aromatic amines.