Asymmetric Bromination Reaction Involving Chiral Pentacarboxycyclopentadienyl Bromide

Optically activeα-halogenated compounds are useful synthetic intermediates in natural products and medicines.Over the past few decades,many novel methods have been developed to access chiralα-halogenated carbonyl compounds as synthetic building blocks.While much focus has been placed on asymmetric synthesis ofα-fluorinated andα-chlorinated carbonyl compounds,significantly less attention is devoted to the correspondingα-bromination methods.Considering the higher reactivity of bromide as a leaving group in S_N2 reactions,development of new asymmetric bromination reagents is still highly desired.This article has mainly discussed the design and synthesis of a novel chiral pentacarboxycyclopentadienyl bromide(PCCP-Br).The prochiral enol silyl ethers can react with the new chiral pentacarboxycyclopentadienyl bromide(PCCP-Br)to give theα-bromoketones with up to 99%yield and up to 77%ee.In addition,when the reaction uses diethyl dibromomalonate as the achiral bromine source,the catalytic cycle can be achieved under 10 mol%chiral pentacarboxycyclopentadienyl bromide and 10 mol%Lewis acid.While,the chiral pentacarboxycyclopentadienyl bromide(PCCP-Br)behaves generally in double bond addition halogenation reaction with cinnamyl alcohol.The dibrominated product yield can be up to 76%and ee value is up to 1%;chlorobromide product yield is up to 45%and ee value is up to 9%.In summary,the synthesis ofα-bromoketone by asymmetric bromination reaction of enol silyl ether with the involvement of chiral cyclopentadienyl bromide was mainly investigated,and a new method for synthesizingα-bromo-bromoketone was developed,the addition halogenation reaction of cinnamyl alcohol was also explored.Compared with other common brominating reagents,the synthesis of chiral pentacarboxycyclopentadienyl bromide is simpler and more economical which does not require complex steps in the synthesis process and the raw material price is very cheap,we believe that these chiral brominating reagents have other potential to be explored in other asymmetric bromination reactions.