Stereoselective Synthesis of Arylglycine Derivatives via Palladium-Catalyzed α-Arylation of a Chiral Nickel(II) Glycinate

Abstract

A practical and efficient stereoselective synthesis of arylglycine derivatives was realized via palladium-catalyzed α-arylation of a chiral nickel(II) glycinate complex with aryl bromides. The structurally diverse arylglycine products were obtained in excellent isolated yields and with good diastereoselectivity. A simple acidic hydrolysis furnished optically pure arylglycines in high yield, and the chiral ligand (S)-BPB could be efficiently recovered and reused.

Reprogramming natural proteins using unnatural amino acids

“…Therefore, an extensive study on enantioselective, catalytic, and chiral pool synthesis of optically pure UAAs has been reported in recent years. [43][44][45][46][47][48][49][50][51] Further study in the design of novel catalysts and chiral auxiliaries, as well as proper selection of chiral precursors for chiral pool synthesis, could enhance the synthesis of chiral UAAs with an excellent enantiomeric excess (ee) and high yield. Consideration of the green chemistry approach towards the asymmetric synthesis of UAAs is highly recommended.…”

“…Numerous approaches for synthesizing acyl glycines have been developed, but only limited asymmetric approaches have been reported. 46 Unlike biocatalysts which most commonly display enantioselectivity, prochiral substrates involving organic and inorganic catalysts rarely exhibit enantioselectivity. Zhang and colleagues demonstrated a stereoselective synthesis of optically active aryl glycine derivatives 49 utilizing a Pd-catalysed alpha arylation of chiral nickel( ii ) glycinate complex 50 with different aryl bromides with up to 80% yield ( Fig.…”

Design and Synthesis of Amino Acid Derivatives via Diethyl Acetadimalonate and Late‐Stage Modification by Chemical Methods

“…Amino acids are important building blocks in design of a wide range of pharmaceuticals, agrochemicals, peptidomimetics with antiviral and oncological applications. [1][2][3] In addition, these building blocks are useful in designing natural products, antibiotics, such as bacitracin and vancomycin [4] and in the synthesis of peptides like insulin. [5] Two types of α-amino acids are available such as proteinogenic and non-proteinogenic αamino acids (AAAs), and all proteinogenic amino acids are chiral except glycine.…”

Synthesis of Unprotected 2-Arylglycines by Transamination of Arylglyoxylic Acids with 2-(2-Chlorophenyl)glycine

“… , Although the Strecker synthesis is their most reliable preparation method, it requires toxic cyanide reagents and harsh conditions for hydrolysis of the α-amino nitriles . Harmless and effective alternative methods have also been developed, including the addition of arylboronic acids to α-imino acids (Petasis reaction), reduction of α-iminoesters, α-arylation of glycine derivatives, and carboxylation using CO 2 as a C1 source for benzyl amine derivatives. , These methods afford protected 2-arylglycines, which require an additional step for deprotection to access unprotected 2-arylglycines. There are few methods to directly prepare unprotected 2-arylglycines .…”