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

Abstract

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.

Alkyl Halide‐Free Heteroatom Alkylation and Epoxidation Facilitated by a Recyclable Polymer‐Supported Oxidant for the In‐Flow Preparation of Diazo Compounds

“…We focused initially on heteroatom alkylation. N ‐Alkylation using metal carbenes, sometimes referred to as NH insertion,21,22 is well established for anilines, amides and carbamates, and has been of interest in our laboratory for some years 23–27. Therefore flowing the diazo‐containing dichloromethane solutions direct from the reactor into solutions containing rhodium(II) acetate dimer and the NH substrate in dichloromethane resulted in formation of a very wide range of desired alkylation products 25 – 42 (Scheme ).…”

A Versatile Enantioselective Catalytic Cyclopropanation‐Rearrangement Approach to the Divergent Construction of Chiral Spiroaminals and Fused Bicyclic Acetals

“…α‐Diazoketones are considered as useful building blocks in organic synthesis and have received a steadily interest due to its distinct reactivity . Significant progresses in catalytic asymmetric reaction with α‐diazoketones have been made, such as asymmetric X‐H insertion reactions, asymmetric cyclopropanations, tandem reactions and others . Pioneered in 1990s, the CP‐RA (cyclopropanation‐rearrangement) strategy has been developed to synthesize racemic bicyclic acetals with diazo‐1,3‐dione and dihydrofuran in a rhodium carbene chemistry .…”

Enantioselective Synthesis of Chiral Amines via Biocatalytic Carbene N–H Insertion

“…14,15,36,37 The difficulty in achieving high enantioselectivity in these reactions have been attributed to catalyst poisoning by the nucleophilic amine and facile dissociation of the ylide intermediate from the metal center. 14,37 While significant progress was made toward overcoming these challenges, these chemocatalytic protocols require the use of precious metals (e.g., Rh, Pd), [38][39][40][41] synthetically challenging chiral ligands and/or co-catalysts, 38,[42][43][44] and/or are restricted to -aryl diazo compounds, 40,41,45 with only a few exceptions. 43,44 In this context, the development of biocatalytic alternatives would be therefore highly desirable as it will contribute to the development of sustainable and environmentally benign approaches for realizing these transformations.…”