Sequential Reductive Amination‐Hydrogenolysis: A One‐Pot Synthesis of Challenging Chiral Primary Amines

Abstract

Difficult-to-access chiral primary amines were formed in good to high yield and ee using a rare example of a one-pot synthesis from prochiral ketones (sequential reductive amination-hydrogenloysis). As a highlight we also demonstrate a one-pot reductive amination-hydrogenolysis-reductive amination (five reactions) of ortho-methoxyacetophenone resulting in the chiral diamine 1-(2-methoxy-A C H T U N G T R E N N U N G phenyl)ethyl-(2-pyridylmethyl)-amine (4) (58% overall yield, > 99% ee), a new organocatalyst for aqueous enantioselective aldol reactions.

Highly Functionalized 1,2–Diamino Compounds through Reductive Amination of Amino Acid-Derived β–Keto Esters

“…Unfortunately, an attempt to optimize this Ti(O i Pr) 4 -mediated process, which included heating the mixture of the ketoester and the amine in neat Ti(O i Pr) 4 (no solvent), was unsuccessful (Table S2, entry 8). The assay to reduce the preformed imine/enamine intermediates in the presence of a heterogeneous hydrogenation catalyst (Pd-C, 50°C, 45 psi), a method that have worked very well for other substrates [23], [31], was also unproductive in this case, resulting in the partial reversion to the initial β-ketoester (Table S2, entry 17).…”

Dynamic Double Kinetic Resolution of Amines and Alcohols under the Cocatalysis of Raney Nickel/Candida antarctica Lipase B: From Concept to Application

“…1 Supporting Information (see footnote on the first page of this article): Experimental details, GC and HPLC data of DDKR process of alcohols, amines, and mexiletine as well as NMR spectra. 1 Supporting Information (see footnote on the first page of this article): Experimental details, GC and HPLC data of DDKR process of alcohols, amines, and mexiletine as well as NMR spectra.…”

“…[1] Lipase-catalyzed kinetic resolution (KR) and dynamic kinetic resolution (DKR) are widely used for the preparation of optically active amines and alcohols. [1] Lipase-catalyzed kinetic resolution (KR) and dynamic kinetic resolution (DKR) are widely used for the preparation of optically active amines and alcohols.…”

Formal Intermolecular Hydroamination of Unbiased Olefins for Primary Amine Formation

“…Hence, most reported examples involve several steps or involve the use of protected amines to form secondary or tertiary amine products from olefins 8,11–17. Additional deprotection or hydrogenolysis steps are required to convert the secondary or tertiary amine into a primary amine 18. Given the broad utility of primary amines, the development of efficient methods for the synthesis of primary amines remains important.…”