Catalytic, Asymmetric Indolizidinone Aza-Quaternary Stereocenter Synthesis: Expedient Synthesis of the Cylindricine Alkaloid Core

• Published in: Organic letters Vol. 15; no. 10; pp. 2346 - 2349
• Main Authors: Dalton, Derek M, Rovis, Tomislav
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 17-05-2013
• Subjects: Alkaloids - chemical synthesis; Alkaloids - chemistry; Catalysis; Cycloaddition Reaction; Heterocyclic Compounds, 3-Ring - chemical synthesis; Heterocyclic Compounds, 3-Ring - chemistry; Indolizines - chemical synthesis; Indolizines - chemistry; Molecular Structure; Quinolones - chemical synthesis; Quinolones - chemistry; Rhodium - chemistry; Stereoisomerism
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/ol400529k

The Rh(I)•CKphos catalyzed [2 + 2 + 2] cycloaddition of 1,1-disubstituted alkenyl isocyanates and alkyl alkynes selectively forms previously inaccessible vinylogous amide indolizidinone cycloadducts, establishing an aza-quaternery stereocenter with excellent enantioselectivities (up to 98% ee). This advance enables a seven step catalytic, asymmetric synthesis of the tricyclic core of the cylindricine alkaloids with excellent control of product selectivity as well as regio- and enantioselectivity.