Herein, we report a nine-step synthesis of belzutifan enabled by a novel Rh-catalyzed asymmetric hydrogenation to install the contiguous fluorinated stereocenters with high enantioselectivity. Moreover, the final ketone reduction in the synthesis proceeds with high diastereoselectivity, leading to the expedient assembly of the stereotriad. In contrast to the original 16-step synthesis, this route avoids a lengthy bromination–oxidation sequence and introduces the sulfone functionality via nucleophilic aromatic substitution, obviating the need for transition metal catalysis.

中文翻译：

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通过 Rh 催化氢化实现 Belzutifan 的对映体和非对映体选择性全合成

在此，我们报道了 Belzutifan 的九步合成，通过一种新型 Rh 催化的不对称氢化来安装具有高对映选择性的连续氟化立体中心。此外，合成中最终的酮还原以高非对映选择性进行，从而导致立体三联体的便捷组装。与最初的 16 步合成相比，该路线避免了冗长的溴化-氧化序列，并通过亲核芳香取代引入了砜官能团，从而无需过渡金属催化。