A domino Kornblum-DeLaMare/aza-Michael reaction of 3,6-dihydro-1,2-dioxines and application to the synthesis of the ceramide transport inhibitor (+/-)-HPA-12

作者：Legendre Sarah V A M; Jevric Martyn; Klepp Julian; Sumby Christopher J; Greatrex Ben W^*

来源：Tetrahedron, 2018, 74(12): 1229-1239.

DOI：10.1016/j.tet.2017.11.010

• Kornblum-DeLaMare rearrangement
• Conjugate addition
• Endoperoxide
• Domino reaction

A Kornblum-DeLaMare/aza-Michael reaction of 3,6-dihydro-1,2-dioxines with primary and secondary amines has been developed which affords 4-hydroxy-3-aminoketones. The aza-Michael products were reduced using non-selective NaBH4/MeOH or diastereoselective (up to 92:8) SnCl4/NaBH4 conditions yielding (1R*,3S*)-3-amino-1,4-diols in up to 97% and 70% yield respectively. The major reduction product was converted in two steps to (+/-)-HPA-12, which is an inhibitor of the cytosolic ceramide transporting protein.

• 出版日期2018-3-22