Activation of Allylic Primary Alcohols With Biaryl Oxazepine Reagent for Chiral Phosphoric Acid‐Catalyzed Asymmetric S N 1 Reaction

Carbocations have long been important reactive intermediates in organic synthesis. Nevertheless, their inherent instability and high reactivity present formidable challenges to achieving precise stereocontrol. Previous strategies require the chiral catalyst to establish an optimal chiral environment around the carbocations, thus, high enantioselectivity can be obtained in these S N 1 reactions. Herein, we report a chiral phosphoric acid (CPA)‐catalyzed S N 1 reaction of primary allylic alcohol, in which the leaving group can modulate the reactivity and control enantioselectivity by forming a complex with the chiral catalyst. The key to the success of this reaction is the development of an alcohol activation reagent (biaryl oxazepine), which can chemoselectively activate allylic alcohol to form an intermediate with good leaving ability. A series of allylic 5,6‐dihydrophenanthridine and 6 H ‐benzo[ c ]chromene products could be obtained in high yields with excellent enantioselectivities. Further transformations and applications of the resulting 5,6‐dihydrophenanthridine derivatives and the asymmetric formal total synthesis of several natural products demonstrated the utilities of this reaction. Mechanistic studies support that the reaction proceeds via an S N 1 pathway, in which the enantio‐control of allyl carbocations was achieved by in situ formed complex from chiral catalysts and leaving groups.