Accessing chiral 2,2-disubstituted morpholines via organocatalytic enantioselective chlorocycloetherification

Chiral morpholine is an important scaffold in organic synthesis and a pharmacophore in medicinal chemistry. However, catalytic enantioselective procedures for the construction of morpholines remain sparse. We report herein a catalytic asymmetric halocyclization protocol to furnish morpholines containing a quaternary stereocenter using cinchona alkaloid-derived phthalazine as the catalyst. Various chlorinated 2,2-disubstituted morpholines are achieved from alkenol substrates in excellent yields and enantioselectivities under mild conditions.

Automated summary

A catalytic asymmetric halocyclization protocol has been developed to synthesize morpholines containing a quaternary stereocenter. Various chlorinated 2,2-disubstituted morpholines were obtained in excellent yields and enantioselectivities under mild conditions using cinchona alkaloid-derived phthalazine as the catalyst.