Abstract
The restricted availability, expense and toxicity of precious metal catalysts such as rhodium and palladium challenge the sustainability of synthetic chemistry. As such, nickel catalysts have garnered increasing attention as replacements for enyne cyclization reactions. On the other hand, bridged tricyclo[5.2.1.01,5]decanes are found as core structures in many biologically active natural products; however, the synthesis of such frameworks with high functionalities from readily available precursors remains a significant challenge. Herein, we report a nickel-catalyzed asymmetric domino cyclization reaction of enynones, providing rapid and modular synthesis of bridged tricyclo[5.2.1.01,5]decane skeletons with three quaternary stereocenters in good yields and remarkable high levels of regio- and enantioselectivities (92–99% ee).
Highlights
The restricted availability, expense and toxicity of precious metal catalysts such as rhodium and palladium challenge the sustainability of synthetic chemistry
The limited output for these challenging molecules may be due to the difficulty in asymmetric synthesis of the bridged tricyclo[5.2.1.01,5]decane core[9,10,11,12], which hinders any further study on their potential bioactive properties
As such, increasing attention has been focused on the development and use of earth-abundant and sustainable element, especially nickel catalysts, to replace these highly expensive and scarce metals in 1,n-enyne cyclization
Summary
The restricted availability, expense and toxicity of precious metal catalysts such as rhodium and palladium challenge the sustainability of synthetic chemistry. Significant efforts have been directed towards the development of asymmetric domino reactions, where the focus has been on the efficient synthesis of biologically important and highly functionalized chiral carbo- and heterocyclic compounds. In this context, the bridged tricyclo [5.2.1.01,5]decanes are found as core structures in many bioactive natural products, including Schincalide A3 and Illisimonin A4 (Fig. 1). We envisioned that the introduction of a 1,3-cyclopentanedione functionality on the 1,6-enyne moiety might facilitate a domino arylnickelation of alkyne/Heck cyclization with alkene/nucleophilic addition to ketone sequence, and provides an expedient access to biologically important bridged tricyclo [5.2.1.01,5] decanes (Fig. 2c). Another challenge is that ketones are more electrophilic than unactivated alkenes, the direct cyclization of alkynes and ketones may take place preferentially, while unactivated alkenes do not participate in the cyclization process[34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50]
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