Well-Defined Binuclear Chiral Spiro Copper Catalysts for Enantioselective N–H Insertion

Abstract

An asymmetric N-H insertion of α-diazoesters with anilines catalyzed by well-defined copper complexes of chiral spiro bisoxazoline ligands was studied in detail. The copper-catalyzed asymmetric N-H insertion of a wide range of α-alkyl-α-diazoacetates with anilines was accomplished with excellent enantioselectivity (up to 98% ee) and provided an efficient method for the preparation of optically active α-amino acid derivatives. A correlation study of the electronic properties of the substrates with the enantioselectivity of the N-H insertion reaction supports a stepwise insertion mechanism, and the significant first-order kinetic isotope effect proves that the proton transfer is most likely the rate-limiting step. A binuclear chiral spiro copper catalyst having 14-electron copper centers, a trans coordination model, a perfect C(2)-symmetric chiral pocket, and significant Cu-Cu interaction was isolated and extensively studied. The novel structure of the binuclear chiral spiro copper catalyst leads to unique reactivity as well as enantioselectivity in the N-H insertion reaction.

Modern Organic Synthesis with α-Diazocarbonyl Compounds

“…497 Besides α-diazopropionates, other α-alkyl-α-diazoacetates underwent the insertion reaction smoothly, with excellent yields and high enantioselectivities. 498 For the Zhou methodology to fulfill its full potential in the synthesis of single-enantiomer amino acids, it needs to be general with respect to both the range of diazoester substrates and the N−H component. In its present form, it is deficient in respect to the latter in that it performs poorly or not at all with amines other than anilines.…”

Broadband Light Harvesting and Unidirectional Electron Flow for Efficient Electron Accumulation for Hydrogen Generation

“…Technically, water reduction to hydrogen is a two‐electron‐involved reaction; while for most light harvesters, one photon absorption leads to the generation of one electron . Therefore, the transfer and accumulation of multiple electrons to the active sites of photocatalysts is essential for hydrogen production from water …”

Asymmetric NH Insertion of Secondary and Primary Anilines under the Catalysis of Palladium and Chiral Guanidine Derivatives

“…Alternatively, the intermediacy of a free ylide from which the chiral catalyst has dissociated would result in low enantioselectivity (path C) 1c. 5b As compared with the reaction of primary amines, the NH insertion of secondary amines, such as N ‐alkyl anilines, would generate a more stable ylide intermediate bearing alkyl/aryl substituents at the nitrogen atom. It is reasonable to hypothesize that the relatively high stability of ammonium ylides might facilitate the degeneration of the catalyst‐associated ylide to a free ylide and thus lead to poor enantioselectivity 5b.…”

“…5b As compared with the reaction of primary amines, the NH insertion of secondary amines, such as N ‐alkyl anilines, would generate a more stable ylide intermediate bearing alkyl/aryl substituents at the nitrogen atom. It is reasonable to hypothesize that the relatively high stability of ammonium ylides might facilitate the degeneration of the catalyst‐associated ylide to a free ylide and thus lead to poor enantioselectivity 5b. On the other hand, the more nucleophilic nitrogen atom is inclined to coordinate strongly with the metal center, which may lead to the inactivation of the catalyst.…”