Vara Brandon A, Johnston Jeffrey N
Department of Chemistry & Vanderbilt Institute of Chemical Biology, Vanderbilt University , Nashville, Tennessee 37235-1822, United States.
J Am Chem Soc. 2016 Oct 26;138(42):13794-13797. doi: 10.1021/jacs.6b07731. Epub 2016 Oct 17.
Preparation of a range of enantioenriched β-fluoro amines (α,β-disubstituted) is described in which the nitrogen and fluorine atoms are attached to sp-hybridized carbons. The key finding is a chiral bifunctional Brønsted acid/base catalyst that can deliver β-amino-α-fluoro nitroalkanes with high enantio- and diastereoselection. A denitration step renders the nitro group "traceless" and delivers secondary, tertiary, or vinyl alkyl fluorides embedded within a vicinal fluoro amine functional group. A synthesis of each possible stereoisomer of a β-fluoro lanicemine illustrates the potential ease with which fluorinated small molecules relevant to neuroscience drug development can be prepared in a stereochemically comprehensive manner.
本文描述了一系列对映体富集的β-氟胺（α,β-二取代）的制备方法，其中氮原子和氟原子连接在sp杂化的碳原子上。关键发现是一种手性双功能布朗斯特酸/碱催化剂，它能够以高对映选择性和非对映选择性提供β-氨基-α-氟硝基烷烃。脱硝基步骤使硝基“无痕”，并得到嵌入在邻位氟胺官能团中的仲、叔或乙烯基烷基氟化物。β-氟拉尼西明的每种可能立体异构体的合成说明了以立体化学全面的方式制备与神经科学药物开发相关的氟化小分子的潜在简便性。
