Theoretical and experimental NMR studies of the Swern oxidation of methyl 6α,7β-dihydroxyvouacapan-17β-oate

This work describes the synthesis of new derivatives of 6 α ,7 β -dihydroxyvouacapan-17 β -oic acid ( 1 ) employing the Swern method for the oxidation of C-6 and C-7 of methyl 6 α ,7 β -di-hydroxyvouacapan-17 β -oate ( 2 ) and the formation of methyl 6,7-dioxovouacapan-17 β -oate ( 3 ). NMR structural studies associated with theoretical calculations of reaction intermediates and products are also reported. The mixture of methyl 7 β -hydroxy-6-oxovouacapan-17 β -oate ( 4 ; 21%) and methyl 6 α -hydroxy-7-oxovouacapan-17 β -oate ( 5 ; 79%) was the product from the first step of the oxidation of 2 . The lower energy of 5 , calculated by HF/6-31G* and DFT/BLYP/6-31G* methods, reinforces the thermodynamic control proposed for the reaction. After further Swern oxidation of the mixture of 4 and 5 , the isomeric form methyl 6-hydroxy-7-oxovouacap-5-en-17 β -oate ( 6 ) was obtained. Theoretical calculations indicate a lower energy for the mono-enol 6 than the 1,2-diketo 3 and the other mono-enol methyl 7-hydroxy-6-oxovouacap-7-en-17 β -oate ( 7 ).