In this report we present the first successful homogenous asymmetric hydrogenation of heavily hindered and minimally functionalized tetrasubstituted cyclic olefins bearing three aromatic substituents, which represent key precursors of lasofoxifene tartrate. The success of our hydrogenation method is based on the surprising discovery that Brønsted acids or Lewis acids can significantly enhance the reactivity of these substrates towards hydrogenation with Ir–P^N complexes. Iterative screens of Ir–P^N catalysts, additives and reaction conditions led to high to full conversions with high ee. The obtained hydrogenation products are easily converted to optically pure selective estrogen receptor modulator lasofoxifene tartrate in significantly higher overall yield compared to previously reported methods.

中文翻译：

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酸促进的Ir-P ^ N络合物催化严重阻碍的3,4-二苯基-1,2-二氢萘的氢化反应：酒石酸拉索昔芬的不对称合成

在本报告中，我们展示了带有三个芳族取代基的重度受阻和官能度最低的四取代环烯烃的首次成功均质不对称氢化，它们代表酒石酸拉索昔芬的关键前体。我们氢化方法的成功基于令人惊讶的发现，即布朗斯台德酸或路易斯酸可以显着增强这些底物对Ir-P ^ N配合物进行氢化的反应性。Ir-P ^ N催化剂，添加剂和反应条件的迭代筛选导致高ee的高转化率到完全转化率。与先前报道的方法相比，所获得的氢化产物易于以明显更高的总产率转化为光学纯的选择性雌激素受体调节剂酒石酸拉索昔芬。