One-pot Reaction Of Catalytic Asymmetric Addition Of Aryllithiums To Unsaturated Aldehydes And Diastereoselective Epoxidation

Enantioenriched epoxy alcohols are among the most versatile and utile intermediates in asymmetric organic synthesis.These substrates readily undergo regio-and stereoselective ring opening reactions with a wide array of nucleophiles.As a result,they have been employed frequently in the synthesis of natural and non-natural products.The synthesis of epoxy alcohols containing a stereogenic center at the carbinol carbon from achiral materials requires that three contiguous stereocenters be generated diastereo-and enantioselectively.The lack of efficient methods for the desired structure of epoxyalcohols with orientation epoxidation from allyl alcohol has prevented their widespread implementation as key intermediates in organic synthesis.It is a challenging class to find an effective procedure for the asymmetric synthesis of chiral acyclic epoxy alcohols.In this report,we outlined a highly enantio-and diastereoselective one-pot reaction of catalytic asymmetric addition of aryllithiums to unsaturated aldehydes and sequential epoxidation for the efficient asymmetry synthesis of acyclic epoxy alcohols.After metalation of bromo-benzene with n-BuLi at-78 ?,transmetalation was performed at 0 ? with AlCl3 in THF.The resulting solution was then warm to rt.and TMEDA,(S)-BINOL-Ti-based catalyst and unsaturated aldehydes was added.After stirring for 3 h at 40 ?,the resulting allylic alkoxide intermediate is then epoxidized in situ using TBHP in the presence of(S)-BINOL-Ti-based catalyst.Epoxy alcohols with up to three contiguous stereocenters were formed in one pot with excellent enantio-and diastereoselectivity with up to>80%ee,>15:1 dr,>50%yield.Our method took advantage of a highly enantioselective C-C bond-forming reaction to set the initial chirality by producing the chiral allylic alcohols in the first step asymmetric addition reaction.This method represents a highly efficient,stereoselective approach to the synthesis of a wide range of useful acyclic epoxy alcohols that were previously difficult to access.