Efficient Synthesis of cis-3-Substituted Prolines by Bidentate-Assisted Palladium Catalysis

• Published in: European journal of organic chemistry Vol. 2015; no. 1; pp. 142 - 151
• Main Authors: Feng, Ruokun, Wang, Binjie, Liu, Yue, Liu, Zhanxiang, Zhang, Yuhong
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.01.2015; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Amino acids; C-H activation; Chemistry; Chemistry, Organic; Directing groups; Homogeneous catalysis; Palladium; Physical Sciences; Proline; Science & Technology; DIRECTING GROUP; PALLADIUM(II)-CATALYZED ORTHO-OLEFINATION; DIRECT ARYLATION; Proline; Amino acids; UNACTIVATED C(SP)-H; Palladium; METHYLENE C(SP)-H BONDS; C-H BONDS; FUNCTIONALIZATION; C-H activation; Homogeneous catalysis; AMINO-ACIDS; Directing groups; STEREOSELECTIVE-SYNTHESIS; ALKENYLATION
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201403191

A highly effective protocol for the synthesis of C‐3‐substituted prolines has been developed. Pd‐catalyzed C(sp3)–H activation is used for the straightforward functionalization of prolines. The use of an 8‐aminoquinolinecarboxamide directing group allows direct arylation, alkenylation, and alkylation at the C‐3 position of prolines in moderate to high yields with diverse iodo‐ or bromo precursors. The resulting 3‐substituted proline derivatives are important units in many biologically active compounds and are useful promoters for a variety of functional group transformations. A highly effective protocol for the synthesis of C‐3‐substituted prolines has been developed. Pd‐catalyzed C(sp3)–H activation is used for the straightforward functionalization of prolines. The use of an 8‐aminoquinolinecarboxamide directing group allows direct arylation, alkenylation, and alkylation at the C‐3 position of prolines in moderate to high yields with diverse iodo‐ or bromo precursors.