Wang Yingcheng, Mo Mingjie, Zhu Kongxi, Zheng Chao, Zhang Hongbin, Wang Wei, Shao Zhihui
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China.
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
Nat Commun. 2015 Oct 1;6:8544. doi: 10.1038/ncomms9544.
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.
炔丙胺是合成多官能团氨基衍生物、天然产物及生物活性化合物的重要中间体。合成手性炔丙胺的经典方法涉及亚胺的不对称炔基化反应。在此，我们报道了通过碳亲核试剂对C-炔基亚胺的催化不对称加成实现炔丙胺的催化不对称曼尼希型合成的重大进展，最终实现了C-炔基亚胺的高度顺式选择性催化不对称曼尼希反应，该反应可提供具有两个相邻立体中心的顺式构型炔丙胺，以及一种无过渡金属的有机催化不对称方法，通过手性布朗斯特碱催化原位生成的具有挑战性的N-Boc C-炔基亚胺（由前所未有的C-炔基N-Boc-N,O-缩醛制备）与α-取代的β-酮酯和酸性较弱的丙二酸（硫）酯分别作为亲核试剂的不对称曼尼希型反应，高效且实用地合成β-炔基-β-氨基酸。还公开了一种催化活化策略，这可能对催化和合成领域具有广泛的意义。
