Abstract
Among about 150 identified allenic natural products, the exocyclic allenes constitute a major subclass. Substantial efforts are devoted to the construction of axially chiral allenes, however, the strategies to prepare chiral exocyclic allenes are still rare. Herein, we show an efficient strategy for the asymmetric synthesis of chiral exocyclic allenes with the simultaneous control of axial and central chirality through copper(I)-catalyzed asymmetric intramolecular reductive coupling of 1,3-enynes to cyclohexadienones. This tandem reaction exhibits good functional group compatibility and the corresponding optically pure exocyclic allenes bearing cis-hydrobenzofuran, cis-hydroindole, and cis-hydroindene frameworks, are obtained with high yields (up to 99% yield), excellent diastereoselectivities (generally >20:1 dr) and enantioselectivities (mostly >99% ee). Furthermore, a gram-scale experiment and several synthetic transformations of the chiral exocyclic allenes are also presented.
Highlights
Among about 150 identified allenic natural products, the exocyclic allenes constitute a major subclass
Substantial efforts have been devoted to the construction of axially chiral allenes, the strategies to prepare chiral exocyclic allenes are still rare[14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31]
An efficient synthesis of axially chiral exocyclic allenes was achieved by Wang and coworkers through copper(I)/chiral bisoxazoline-catalyzed asymmetric cross-coupling between tetralone-derived diazo compounds and terminal alkynes (Fig. 2b)[35]
Summary
Among about 150 identified allenic natural products, the exocyclic allenes constitute a major subclass. Due to the unique structural features and versatile reactivity of allenes, significant applications have been found in medicinal chemistry and material science, and as important intermediates in synthetic transformations, and chiral ligands or catalysts in asymmetric catalysis[4,5,6,7,8] Among these identified allenic natural products, the exocyclic allenes constitute a major subclass, such as Neoxanthin[9], Grasshopper ketone[10], Citroside A11, and fungal metabolite A82775C12 which bearing a cyclohexylidene ring (Fig. 1). Cycloaddition reaction between racemic allenyl trimethylenemethanes and electron-deficient olefins through a dynamic kinetic asymmetric transformation process, in which the trisubstituted chiral exocyclic allenic products bearing axial and central chirality could be furnished, their diastereoselectivities were relatively insufficient (Fig. 2c)[36] Despite these successful advances, the synthetic methods to prepare the chiral exocyclic allenes are still rare and it is highly desired to develop more practical methods to construct more diverse chiral exocyclic allenes
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