Chiral Ammonium Salts Catalyzed Asymmetric Halogen-initiated Semipinacol Rearrangement

Spirocyclic backbone is widely found in active natural products and drug molecules,so the construction of spirocyclic skeleton has always been the focus of organic synthetic chemists.However,due to the crowding of such skeletons,it is difficult to synthesize the chiral snail ring skeleton containing the quaternary carbon center.The asymmetric halogenated semipinacol rearrangement of allyl alcohol is an effective method for constructing such skeletons,which has been successfully used in the synthesis of active natural products and drug molecules.However,there are some drawbacks: reaction substrates have limitations;The reaction conditions are relatively strict;Catalysts involve metal complexes,complex structures,and high prices;low enantioselectivity of the product;The synthesis steps of the halogenated reagents used are complex and unstable.Therefore,it is important to develop an asymmetric halogenated semipinacol alcohol rearrangement reaction method with mild reaction conditions,wide substrate applicability,and more efficient and simple rearrangement of the reaction conditions.Our research group has been working on the asymmetric phase transfer catalyzed by novel chiral amine salts.Phase transfer catalysis has the advantages of simple operation,cheap and easy solvent availability,green environmental protection,and mild reaction conditions.In this study,it was expected that the asymmetric halosemipinacol rearrangement reaction of allyl alcohol catalyzed by chiral amine salts was expected to construct a chiral spirocyclic skeleton containing a quaternary carbon center.The chiral spirocyclic skeleton containing the quaternary carbon center was successfully constructed by using allyl alcohol derivatives as substrates,chiral phosphoamine catalysts,N-halogen-succinimide as halogenated reagents,and green non-polar solvents as reaction solvents.NBS was used as an electrophilic substitute reagent,and the bromosemipinacol which alcohol rearrangement product had excellent enantioselectivity.Using NIS,DCH and NPSP as electrophilic substitutes,the iodo,chlorinated and selenated semipinacol rearrangement products achieved moderate enantioselectivity.