title: Asymmetric synthesis of syn-propargylamines and unsaturated β-amino acids under Brønsted base catalysis.
abstract: Propargylamines are important intermediates for the synthesis of polyfunctional amino derivatives and natural products and biologically active compounds. The classic method of synthesizing chiral propargylamines involves the asymmetric alkynylation of imines. Here, we report a significant advance in the catalytic asymmetric Mannich-type synthesis of propargylamines through catalytic asymmetric addition of carbon nucleophiles to C-alkynyl imines, culminating in a highly syn-selective catalytic asymmetric Mannich reaction of C-alkynyl imines that provide syn-configured propargylamines with two adjacent stereogenic centres and a transition metal-free organocatalytic asymmetric approach to β-alkynyl-β-amino acids with high efficiency and practicality, via a chiral Brønsted base-catalysed asymmetric Mannich-type reaction of in situ generated challenging N-Boc C-alkynyl imines from previously unreported C-alkynyl N-Boc-N,O-acetals, with α-substituted β-keto esters and less-acidic malonate (thio)esters as nucleophiles, respectively. A catalytic activation strategy is also disclosed, which may have broad implications for use in catalysis and synthesis.
authors.affiliation: Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China.
authors.forename: Yingcheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Mo
authors.affiliation: Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China.
authors.forename: Kongxi
authors.initials: K
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Chemistry &Chemical Biology, University of New Mexico, Albuquerque, New Mexico 87131, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Shao
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000145:classification*; D002384:Catalysis; D015394:Molecular Structure; D011437:Propylamines / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000596:Amino Acids; D011437:Propylamines