Gosselin Francis, O'Shea Paul D, Roy Stéphanie, Reamer Robert A, Chen Cheng-Yi, Volante Ralph P
Department of Process Research, Merck Frosst Centre for Therapeutic Research, 16711 route transcanadienne, Kirkland, Québec, Canada.
Org Lett. 2005 Jan 20;7(2):355-8. doi: 10.1021/ol047431x.
[Reaction: see text] Addition of lithium bis(trimethylsilyl)amide to perfluorinated ketones 1a-j affords (E)-N-TMS-ketimines 2a-j that are reduced in situ to afford racemic perfluoromethylated amine hydrochloride salts 3a-j in 54-97% yields. Solvolysis of the N-Si bond in MeOH leads to formation of bench-stable, isolable N-H imine Z/E isomer mixtures along with a methanol adduct. Enantioselective reduction of these three-component mixtures provides the first catalytic asymmetric synthesis of trifluoromethylated amines in 72-95% yields and 75-98% ee.
[反应：见正文] 将双（三甲基硅基）氨基锂加入全氟酮1a - j中，得到（E）-N-三甲基硅基酮亚胺2a - j，其原位还原得到外消旋全氟甲基化胺盐酸盐3a - j，产率为54 - 97%。N - Si键在甲醇中的溶剂解导致形成易于保存、可分离的N - H亚胺Z/E异构体混合物以及甲醇加合物。对这些三组分混合物进行对映选择性还原，首次实现了三氟甲基化胺的催化不对称合成，产率为72 - 95%，对映体过量值为75 - 98%。
