Application of Mn(III)-catalysed olefin hydration reaction to the selective functionalisation of avermectin B1

The Mn(dpm)₃-catalysed olefin hydration reaction of α,β-unsaturated esters and ketones discovered by Mukaiyama in 1990 and further developed by Magnus in 2000 was applied to the challenging environment of avermectin B₁. Different avermectin substrates such as 4″,7-OTMS-5-oxo-avermectin B₁3, avermectin B₁1 and Δ^2,3-avermectin B₁6 were thus treated with Mn(dpm)₃, PhSiH₃ in isopropanol under oxygen atmosphere to afford several novel analogues, including 3,4-dihydro-3-hydroxy-avermectin B₁8 with high level of regio- and stereoselectivity, 2-hydroxy-3,4-dihydro-avermectin B₁7, the first example of a 2-substituted avermectin and the novel 22,23-dihydro-22-hydroxy-avermectin B₁9a and 9b, epimeric at C(22). Biological activity of these new avermectin derivatives is also reported.