Diastereodivergent Synthesis of β‐Amino Alcohols by Dual‐Metal‐Catalyzed Coupling of Alkoxyallenes with Aldimine Esters

• Published in: Angewandte Chemie International Edition 2021-03, Vol.60 (12), p.6545-6552
• Main Authors: Zhu, Minghui, Zhang, Qinglong, Zi, Weiwei
• Format: Article
• Language: English
• Subjects: Alcohol; Alcohols; amino alcohols; asymmetric catalysis; Catalysts; Coupling; Coupling (molecular); Diastereoisomers; Enantiomers; Esters; Ligands; Metals; Natural products; palladium; stereodivergence; Stereoisomerism; Stereoisomers; Stereoselectivity; synergistic catalysis
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202014510

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. A dual‐metal catalysis was established for the asymmetric coupling of alkoxyallenes with aldimine esters. This method resulted in the diastereodivergent synthesis of β‐amino alcohol motifs. The total synthesis of mycestericins F and G was demonstrated.