State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin, 300071, China.
Angew Chem Int Ed Engl. 2021 Mar 15;60(12):6545-6552. doi: 10.1002/anie.202014510. Epub 2021 Feb 3.
Both syn- and anti-β-amino alcohols are common structural motifs in natural products, drug molecules, chiral ligands and catalysts. However, the currently available methods for synthesizing these motifs are limited to generate only one diastereoisomer. Therefore, development of a unified method for stereoselective access to complementary diastereomers would be highly desirable. Herein, we report a method for dual-metal-catalyzed diastereodivergent coupling of alkoxyallenes with aldimine esters. By carefully selecting the two metals and appropriate chiral ligands, we could synthesize both syn- and anti-β-amino alcohol motifs with high enantioselectivity and diastereoselectivity from the same set of starting materials. Furthermore, stereodivergent syntheses of all four stereoisomers of β-amino alcohols could be achieved. We demonstrated the synthetic utility of this method by concisely synthesizing two β-amino alcohol natural products, mycestericins F and G.
顺式和反式β-氨基醇都是天然产物、药物分子、手性配体和催化剂中的常见结构基序。然而，目前用于合成这些基序的方法仅限于生成一种非对映异构体。因此，开发一种用于立体选择性获得互补非对映异构体的统一方法将是非常可取的。在此，我们报告了一种通过双金属催化烷氧基丙二烯与亚胺酯的非对映选择性偶联来合成顺式和反式β-氨基醇的方法。通过仔细选择两种金属和合适的手性配体，我们可以从同一组起始原料中以高对映选择性和非对映选择性合成顺式和反式β-氨基醇基序。此外，还可以实现β-氨基醇的所有四个立体异构体的立体选择性合成。我们通过简洁地合成两种β-氨基醇天然产物 mycestericins F 和 G 证明了该方法的合成实用性。
