Department of Chemistry, Yale University, New Haven, Connecticut 06520, United States.
Department of Chemistry, University of California, Berkeley, California 94720, United States.
J Am Chem Soc. 2020 Sep 23;142(38):16461-16470. doi: 10.1021/jacs.0c08057. Epub 2020 Sep 14.
The defined structure of molecules bearing multiple stereogenic axes is of increasing relevance to materials science, pharmaceuticals, and catalysis. However, catalytic enantioselective approaches to control multiple stereogenic axes remain synthetically challenging. We report the catalytic synthesis of two-axis terphenyl atropisomers, with complementary strategies to both chlorinated and brominated variants, formed with high diastereo- and enantioselectivity. The chemistry proceeds through a sequence of two distinct dynamic kinetic resolutions: first, an atroposelective ring opening of Bringmann-type lactones produces a product with one established axis of chirality, and second, a stereoselective arene halogenation delivers the product with the second axis of chirality established. In order to achieve these results, a class of Brønsted basic guanidinylated peptides, which catalyze an efficient atroposelective chlorination, is reported for the first time. In addition, a complementary bromination is reported, which also establishes the second stereogenic axis. These bromo-terphenyls are accessible following the discovery that chiral anion phase transfer catalysis by -symmetric phosphoric acids allows catalyst control in the second stereochemistry-determining event. Accordingly, we established the fully catalyst-controlled stereodivergent synthesis of all possible chlorinated stereoisomers while also demonstrating diastereodivergence in the brominated variants, with significant levels of enantioselectivity in all cases.
具有多个立体轴的分子的明确结构对于材料科学、制药和催化越来越重要。然而，控制多个立体轴的催化对映选择性方法在合成上仍然具有挑战性。我们报告了具有互补策略的两个轴联苯非对映异构体的催化合成，对于氯化和溴化变体都形成了高非对映和对映选择性。该化学通过两个不同的动态动力学拆分序列进行：首先，Bringmann 型内酯的立体选择性开环产生具有一个已建立的手性轴的产物，其次，立体选择性芳族卤化反应提供第二个手性轴建立的产物。为了实现这些结果，首次报道了一类催化有效立体选择性氯化的 Brønsted 碱性胍基化肽。此外，还报道了一种互补的溴化反应，该反应也建立了第二个立体轴。在发现 -对称磷酸酸对的手性阴离子相转移催化允许在第二个立体化学决定事件中控制催化剂之后，这些溴代联苯是可获得的。因此，我们建立了所有可能的氯化立体异构体的完全受催化剂控制的立体发散合成，同时还证明了溴化变体中的非对映发散，在所有情况下都具有显著的对映选择性水平。
