title: Highly efficient asymmetric anti-Mannich reactions of carbonyl compounds with N-carbamoyl imines catalyzed by amino-thiourea organocatalysts.
abstract: A series of pyrrolidine-based organocatalysts which bear three synergistic features, i.e. secondary amino group, various H-bond donor groups at the 4-position and a stereocontrol silyl ether group at the α-position of the pyrrolidine nitrogen atom, were developed. They were screened in anti-Mannich reactions of carbonyl compounds with preformed or in situ generated N-protected α-imino ethylglyoxylate and aldehydes with preformed or in situ generated N-carbamoyl imines. The influence of H-bond donor ability at the 4-position was also investigated. Among all the catalysts, 2a was identified as a general efficient organocatalyst suitable for various types of anti-Mannich reactions and broad substrate scope. Excellent results (up to 98% yield, >99% ee and >99 : 1 dr) were achieved with 5 mol% catalyst load. Sulfones with ortho substituents or very strong withdrawing groups on the aromatic ring, which have been regarded as challenging substrates in the direct anti-Mannich reactions of aldehydes with in situ generated N-carbamoyl imines, also worked well. The optimization of our catalytic system also offered alternative and easily operational protocols to access anti-Mannich products with orthogonal N-Boc or N-Cbz protecting groups.
authors.affiliation: School of Chemistry and Chemical Engineering, Southwest University, Chongqing, P R China.
authors.forename: Jiuzhi
authors.initials: J
authors.lastname: Gao
authors.forename: Yongming
authors.initials: Y
authors.lastname: Chuan
authors.forename: Jiali
authors.initials: J
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.forename: Yungui
authors.initials: Y
authors.lastname: Peng
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D002384:Catalysis; D007097:Imines / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism; D013890:Thiourea / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D000447:Aldehydes; D007097:Imines; D007659:Ketones; D011759:Pyrrolidines; D013890:Thiourea