Asymmetric C–C Bond Formation between Chiral N‐Phosphonyl Imines and a Nickel(II)‐Complexed Glycine Schiff Base Provides Efficient Synthesis of α,β‐syn‐Diamino Acid Derivatives

Abstract

The GAP asymmetric synthesis of α,β-diamino acid derivatives has been achieved by reacting chiral N-phosphonyl imines with Ni(II)-complex of glycine ester-based enolate without the use of traditional purifications of chromatography and recrystallization. The successful control of synstereochemistry of vicinal diamino products complements our previous methods which afforded anti stereoisomers and enables all four individual isomers to be synthesized by simply changing enolate geometry. In contrast to our previous synthesis where required at least 5 equiv of glycine Schiff base enolate for complete conversion, the new synthesis only needs 1.1 equiv of glycine Schiff base enolate to give complete diastereoselectivity (>99% de) and yields (91% – 97%). The absolute stereochemistry has been unambiguously determined by X-ray structural analysis.

Cobalt-catalysed site-selective intra- and intermolecular dehydrogenative amination of unactivated sp3 carbons

“…The detailed mechanistic investigations of these transformations are currently undergoing in our laboratory. In the meanwhile, N -phosphonyl and phosphinyl groups will be investigated for the present intra- and intermolecular dehydrogenative amination reactions for achieving the GAP work-up 68 69 .…”

N-Phosphonyl/phosphinyl imines and group-assisted purification (GAP) chemistry/technology

“…Both anti and syn isomers of α,β-diamino esters were obtained by using different anions. [20][21][22] The diamino esters 23 were synthesized from the reaction between lithium glycine enolate and phosphonyl imines 1 (Scheme 14) in excellent yields (up to 97%) and diastereoselectivities (up to 100 : 1 : 0 : 5) 20 Phosphonyl group A gave the highest diastereoselectivities and the anti-stereoisomer was obtained as the major product. n-BuLi was found as the most efficient base for the reaction, while KHMDS did not facilitate progression of the reaction, owing to the poor activation of the phosphonyl imine by the potassium cation.…”

“…The following studies on the stereoselective GAP synthesis of (2R,3S)-α,β-diamino esters were carried out with 19 (Scheme 16). 22 To obtain the Z-enolate for cis-diamino ester formations, the Ni(II)-complex of glycine-derivative 25 was chosen as the enolate source. Different reaction conditions were examined for the reaction between 19 and 25.…”

Squaramide-Catalyzed Asymmetric Mannich Reactions of Azlactones with Isatin-Derived Ketimines: Access to α,β-Diamino Acid Derivatives Bearing Vicinal Quaternary Stereocenters

“…In addition, they are also essential scaffolds broadly distributed in a range of natural products and biologically active compounds . As a consequence, the preparation of such molecules in a catalytic and stereoselective fashion has attracted considerable attention and a series of approaches have been successfully established. , Among them, the direct Mannich reactions between azlactones and imines are of exceptional popularity due to the ready availability and bench stability of both substrates . In the past two decades, the groups of Ooi, Wang, Toste, Gong, Hui, Amarante, and Šebesta have independently employed various chiral catalysts such as tetraamino­phosphonium carboxylates, cinchona alkaloids, gold complexes, bis­(betaine) bases, silver phosphates, phosphoric acids, and bifunctional thioureas to mediate asymmetric Mannich reactions of azlactones with aldimines to construct α,β-diamino acid derivatives bearing adjacent tertiary and quaternary stereocenters (Scheme a).…”