Abstract
Transition-metal-catalyzed tandem Heck/carbonylation reaction has emerged as a powerful tool for the synthesis of structurally diverse carbonyl molecules, as well as natural products and pharmaceuticals. However, the asymmetric version was rarely reported, and remains a challenging topic. Herein, we describe a palladium-catalyzed asymmetric tandem Heck/carbonylation desymmetrization of cyclopentenes. Alcohols, phenols and amines are employed as versatile coupling reagents for the construction of multifunctional chiral bicyclo[3.2.1]octanes with one all-carbon quaternary and two tertiary carbon stereogenic centers in high diastereo- and enantioselectivities. This study represents an important progress in both the asymmetric tandem Heck/carbonylation reactions and enantioselective difunctionalization of internal alkenes.
Highlights
Transition-metal-catalyzed tandem Heck/carbonylation reaction has emerged as a powerful tool for the synthesis of structurally diverse carbonyl molecules, as well as natural products and pharmaceuticals
Transition-metal (TM)-catalyzed carbonylation reaction[1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16], especially palladium-catalyzed tandem Heck/carbonylation reaction, presents an efficient method to construct a variety of synthetically versatile carbonyl compounds from readily accessible organic halides and alkenes[17,18,19,20,21]
These methods have been applied as key steps in the total synthesis of natural products and bioactive molecules[22,23,24,25,26,27,28]
Summary
Transition-metal-catalyzed tandem Heck/carbonylation reaction has emerged as a powerful tool for the synthesis of structurally diverse carbonyl molecules, as well as natural products and pharmaceuticals. In contrast to the success of 1,1-disubstituted alkenes (the alkylpalladium intermediates lack eliminable β-hydrogen), the TM-catalyzed asymmetric tandem Heck/carbonylation reaction of unactivated internal alkenes has not been developed until now. Based on our research interest in Heck reactions[47,48,49,50], we describe a palladium-catalyzed asymmetric tandem Heck/carbonylation desymmetrization of cyclopentenes to construct multifunctional chiral bicyclo[3.2.1]octanes bearing one allcarbon quaternary and two tertiary carbon stereogenic centers in excellent diastereoselectivities and enantioselectivities (Fig. 1b).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
