Catalytic enantioselective construction of axial chirality in 1,3-disubstituted allenes

• Published in: Nature communications 2019-01, Vol.10 (1), p.507-507, Article 507
• Main Authors: Song, Shihua, Zhou, Jing, Fu, Chunling, Ma, Shengming
• Format: Article
• Language: English
• Subjects: 639/638/403/933; 639/638/403/977; 639/638/77/883; Allene; Carbonates; Catalysis; Chirality; Enantiomers; Humanities and Social Sciences; Ligands; Loosening; multidisciplinary; Natural products; Palladium; Science; Science (multidisciplinary); Substitutes; Substrates
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-07908-1

Metal-catalyzed enantioselective construction of the loosening axial allene chirality spreading over three carbon atoms using a chiral ligand is still a significant challenge. In the literature, steric effect of the substrates is the major strategy applied for such a purpose. Herein, we present a general palladium-catalyzed asymmetrization of readily available racemic 2,3-allenylic carbonates with different types of non-substituted and 2-substituted malonates using ( R )-(−)-DTBM-SEGPHOS as the preferred ligand to afford 1,3-disubstituted chiral allenes with 90~96% ee . This protocol has been applied to the first enantioselective synthesis of natural product, ( R )-traumatic lactone. Control experiments showed that in addition to the chiral ligand, conducting this transformation via Procedure C, which excludes the extensive prior coordination of the allene unit in the starting allene with Pd forming a species without the influence of the chiral ligand, is crucial for the observed high enantioselectivity. Highly enantioselective synthesis of allenes has been relying, so far, on the steric hindrance of substrates. Here the authors achieve excellent stereocontrol in the synthesis of chiral allenes with a palladium-DTBM-SEGPHOS catalytic system in a non-substrate-dependent manner.