Development of Dipolarophiles for Catalytic Asymmetric Cycloadditions through Pd‐π‐Allyl Zwitterions

Abstract The development of new and efficient methodology for the construction of optically active molecules is of great interest in both synthetic organic and medicinal chemistry fields. To this end, the personal account summarizes our studies on the development of electron‐deficient alkenes, allenes, and alkynes containing single activator as new dipolarophiles for Pd‐catalyzed asymmetric cycloaddition reactions. These new dipolarophiles can participate in Pd‐catalyzed asymmetric [3+2] and [4+2] cycloadditions through Pd‐π‐allyl 1,3‐ and 1,4‐zwitterions in‐situ generated by the reaction of Pd(0) catalyst with vinyl aziridines, vinyl epoxides, vinyl cyclopropanes, 4‐vinyl‐1,3‐dioxan‐2‐ones, and vinyl benzoxazinanones. These [3+2] and [4+2] cycloadditions provide efficient approaches to a wide range of enantiomerically enriched five‐ and six‐membered ring compounds containing contiguous chiral centers with high to excellent chemo‐, diastereo‐, and enantioselectivities. The utilities of these protocols are demonstrated by transformation of the cycloadducts into other useful chiral building blocks. DFT calculations reveal the dissimilar reactivity of different electron deficient alkenes and rationalize the mechanism and stereo‐control of the reaction. A Pd‐catalyzed inverse [3+2] cycloaddition is disclosed.