Hexafluoroisopropanol-Induced Facial Selectivity in a Hindered Diels-Alder Reaction

BRD4780 is a small molecule that can selectively clear mutant MUC1-fs protein in mucin kidney disease models. Prior syntheses of BRD4780 were unsuitable for preparation on large scale. In this manuscript, HFIP is described as a unique solvent that allowed the key Diels- Alder reaction to proceed with >20:1 endo diastereoselectivity, enabling the kg-scale preparation of BRD4780 for further studies.