Center for Heterocyclic Compounds, Department of Chemistry, University of Florida , Gainesville, Florida 32611, United States.
J Am Chem Soc. 2017 Mar 8;139(9):3352-3355. doi: 10.1021/jacs.7b00363. Epub 2017 Feb 21.
By the nature of its structure, the 5-membered chiral biaryl heterocyclic scaffold represents a departure from 6-membered P,N-ligands that facilitates tuning and enables ligand evolution to address issues of selectivity and reactivity. In this vein, the Cu-catalyzed enantioselective conjugate alkynylation of Meldrum's acid acceptors is reported using Me-StackPhos. Enabled by this new ligand, the reaction tolerates a wide range of alkynes furnishing the products in high yields and excellent enantioselectivity. The transformation provides access to highly useful chiral β-alkynyl Meldrum's acid building blocks as demonstrated by an efficient enantioselective synthesis of the preclinical agent OPC 51803.
五元手性联芳杂环骨架的结构性质使其有别于六元 P,N-配体，这有利于调节并实现配体的演变，以解决选择性和反应性问题。本着这种精神，本文使用 Me-StackPhos 报道了 Meldrum's 酸受体的铜催化对映选择性共轭炔基化反应。在这种新型配体的作用下，该反应可以容忍广泛的炔烃，以高产率和优异的对映选择性得到产物。该转化提供了高价值的手性β-炔基 Meldrum's 酸砌块，临床前药物 OPC 51803 的高效对映选择性合成就证明了这一点。
