Heterogeneous Copper-Catalyzed Cross-Coupling for Sustainable Synthesis of Chiral Allenes: Application to the Synthesis of Allenic Natural Products.

Abstract

Classical Crabbé type SN 2' substitutions of propargylic substrates has served as one of the standard methods for the synthesis of allenes. However, the stereospecific version of this transformation often requires either stoichiometric amounts of organocopper reagents or special functional groups on the substrates, and the chirality transfer efficiency is also capricious. Herein, we report a sustainable methodology for the synthesis of diverse 1,3-di and tri-substituted allenes by using a simple and cheap cellulose supported heterogeneous nanocopper catalyst (MCC-Amp-Cu(I/II)). This approach represents the first example of heterogeneous catalysis for the synthesis of chiral allenes. High yields and excellent enantiospecificity (up to 97 % yield, 99 % ee) were achieved for a wide range of di- and tri-substituted allenes bearing various functional groups. It is worth noting that the applied heterogeneous catalyst could be recycled at least 5 times without any reduced reactivity. To demonstrate the synthetic utility of the developed protocol, we have applied it to the total synthesis of several chiral allenic natural products.