Synthesis of 6-oxy functionalized campest-4-en-3-ones: efficient hydroperoxidation at C-6 of campest-5-en-3-one with molecular oxygen and silica gel

Abstract

As a reference compound library for the investigation of biosynthesis of brassinosteroids, focused on a pathway from campesterol ( 1) to campestanol ( 2), 6-oxy functionalized campest-4-en-3-ones as well as campest-5-en-3-one ( 7) and campestane-3,6-dione were prepared from 1. Oxidation of 1 with pyridinium chlorochromate buffered by calcium carbonate gave 5-en-3-one ( 7) in 76% yield. Treatment of 7 with silica gel under an oxygen atmosphere in ethyl ether at room temperature produced efficient hydroperoxidation at the C-6 position to give 6α-hydroperoxycampest-4-en-3-one and 6β-hydroperoxycampest-4-en-3-one in 34% and 49% yields, respectively. These compounds were converted to 6α-hydroxycampest-4-en-3-one and 6β-hydroxycampest-4-en-3-one by reduction with triethyl phosphite. This provided the first example of the practical use of hydroperoxidation at C-6 of a Δ 5(6)-unsaturated 3-oxo-steroid with molecular oxygen and silica gel. On the other hand, oxidation of 1 with pyridinium chlorochromate in the absence of calcium carbonate gave campest-4-ene-3,6-dione in 64% yield. This compound was then converted in a highly stereoselective manner to campestane-3,6-dione with A/B trans ring junction by reduction with titanium (III) chloride in 85% yield.