Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, USA.
Nat Chem. 2016 Aug;8(8):768-77. doi: 10.1038/nchem.2523. Epub 2016 May 23.
Organofluorine compounds are central to modern chemistry, and broadly applicable transformations that generate them efficiently and enantioselectively are in much demand. Here we introduce efficient catalytic methods for the addition of allyl and allenyl organoboron reagents to fluorine-substituted ketones. These reactions are facilitated by readily and inexpensively available catalysts and deliver versatile and otherwise difficult-to-access tertiary homoallylic alcohols in up to 98% yield and >99:1 enantiomeric ratio. Utility is highlighted by a concise enantioselective approach to the synthesis of the antiparasitic drug fluralaner (Bravecto, presently sold as the racemate). Different forms of ammonium-organofluorine interactions play a key role in the control of enantioselectivity. The greater understanding of various non-bonding interactions afforded by these studies should facilitate the future development of transformations that involve fluoroorganic entities.
有机氟化合物是现代化学的核心，人们迫切需要能够高效和对映选择性地生成它们的广泛适用的转化方法。在这里，我们介绍了一种有效的催化方法，用于将烯丙基和烯丙基有机硼试剂加成到氟取代的酮上。这些反应由易于获得且价格低廉的催化剂促进，以高达 98%的收率和>99:1 的对映体过量比提供了多功能且难以获得的叔同型烯丙醇。该方法的实用性通过一种简洁的对映选择性方法得到了突出体现，该方法用于合成抗寄生虫药物氟虫腈（Bravecto，目前以外消旋体形式出售）。不同形式的铵-有机氟相互作用在对映选择性控制中起着关键作用。这些研究提供的对各种非键相互作用的更深入了解，应有助于未来涉及含氟有机实体的转化的发展。
