Large-Scale Synthesis of the Glycine Schiff Base Ni(II) Complex Derived from (S)- and (R)-N-(2-Benzoyl-4-chlorophenyl)-1-[(3,4-dichlorophenyl)methyl]-2-pyrrolidinecarboxamide

被引：19

作者：

Romoff, Todd T. ^{[1
]}

Ignacio, Bernardo G. ^{[1
]}

Mansour, Noel ^{[1
]}

Palmer, Andrew B. ^{[1
]}

Creighton, Christopher J. ^{[1
]}

Abe, Hidenori ^{[4
]}

Moriwaki, Hiroki ^{[4
]}

Han, Jianlin ^{[5
]}

Konno, Hiroyuki ^{[6
]}

Soloshonok, Vadim A. ^{[2
,3
]}

机构：

[1] Hamari Chem USA, San Diego, CA 92121 USA

[2] Univ Basque Country, UPV EHU, San Sebastian, Spain

[3] Basque Fdn Sci, Bilbao, Spain

[4] Hamari Chem Ltd, Osaka, Japan

[5] Nanjing Forestry Univ, Nanjing, Peoples R China

[6] Yamagata Univ, Yamagata, Japan

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2020年 / 24卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Tailor-made amino acids; chiral glycine equivalents; nickel(II) complexes; Schiff bases; asymmetric synthesis; ALPHA-AMINO-ACIDS; EFFICIENT ASYMMETRIC-SYNTHESIS; PURE 4-AMINOGLUTAMIC ACIDS; MICHAEL ADDITION-REACTIONS; VIRTUALLY COMPLETE CONTROL; NUCLEOPHILIC GLYCINE; OPERATIONALLY CONVENIENT; ALDOL REACTIONS; FACE DIASTEREOSELECTIVITY; CHIRAL NI(II)-COMPLEX;

D O I：

10.1021/acs.oprd.9b00399

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

Non-natural, tailor-made amino acids are of crucial importance to the synthesis of bioactive peptides and new chemical entities. Innovative methodology is always needed for the preparation of enantiomerically pure amino acids that does not rely on tedious resolution procedures. We report here the multikilogram scale synthesis of the chiral nucleophilic glycine equivalent Ni(II) complexes (S)-19 and (R)-19 derived from (S)- and (R)-N-(2-benzoyl-4-chlorophenyl)-1-[(3,4-dichlorophenyl)methyl]-2-pyrrolidinecarboxamide. Replacement of the traditional carbonate bases with the soluble organic base DBU for synthesis resulted in improved process efficiency, safety, and yield. The issue of partial racemization of the proline moiety is critically addressed, and enantiomeric purities in excess of 99.5% ee are routinely achieved in this manufacture.

引用

页码：294 / 300

页数：7

共 65 条

[11] Syntheses and Transformations of α-Amino Acids via Palladium-Catalyzed Auxiliary-Directed sp3 C-H Functionalization [J].