Davenport Research Laboratories, Department of Chemistry, University of Toronto , 80 St. George Street, Toronto, Ontario M5S 3H6, Canada.
J Am Chem Soc. 2017 Aug 23;139(33):11357-11360. doi: 10.1021/jacs.7b07104. Epub 2017 Aug 15.
Metal homoenolates, produced via C-C bond cleavage of cyclopropanols, have been extensively investigated as nucleophiles for the synthesis of β-substituted carbonyl derivatives. Herein, we demonstrate that zinc homoenolates can react as carbonyl-electrophiles in the presence of nucleophilic amines to yield highly valuable trans-cyclopropylamines in good yields and high diastereoselectivities. GSK2879552, a lysine demethylase 1 inhibitor currently in clinical trials for the treatment of small cell lung carcinoma, was synthesized using this strategy.
金属偕嗯醇盐通过环丙醇 C-C 键的断裂生成，被广泛研究作为亲核试剂用于β-取代的羰基衍生物的合成。在此，我们证明锌偕嗯醇盐在亲核胺的存在下可以作为羰基亲电试剂反应，以高产率和高非对映选择性得到高价值的反式环丙基胺。GSK2879552，一种赖氨酸去甲基酶 1 抑制剂，目前正在临床试验中用于治疗小细胞肺癌，就是使用这种策略合成的。
