CHIRAL LITHIOMETHYL ETHERS BY DTBB-CATALYZED CHLORINE-LITHIUM EXCHANGE

The reaction of equimolecular amounts of enantiomerically pure (+)- or (-)- chloromethyl menthyl ethers 1, or the phenyl derivative (-)-4 an d an electrophile [Me3SiCl, (BuCHO)-C-t, PhCHO, (CH2)(4)CO, Et2CO, PhC OMe, Ph2CO, HCONMe2, PhCH=NPh] with an excess of lithium powder (1:7 m olar ratio) and a catalytic amount of DTBB (5 mol %) in THF at 0 degre es C (Method A) leads, after hydrolysis, to the corresponding function alized chiral ethers 2 and 5. The reaction can be also carried out in a two step process: tandem lithiation at -90 degrees C followed by rea ction with the electrophile (H2O, D2O) at the same temperature (Method B). When prochiral electrophiles are used ((BuCHO)-C-t, PhCHO, PhCOMe , PhCH=NPh), low asymmetric induction (<1:2) is obtained.