Selective Synthesis of Deuterated cis- and trans-Isohumulones and trans-Isohumulinones

Deuterated isohumulones can be prepared directly from humulones by an acyloin ring contraction under either magnesium catalyzed basic conditions or photochemical induced reaction in deuterated solvents. Reaction of humulones with biphasic methylene chloride/aqueous NaOD and MgSO4 in D2O gave stereoselective formation of cis-3d- isohumulones (cis-trans ratio of 82:18) as the magnesium salts in 71-83% yield. Greater than 95% incorporation of three deuterons was observed in the C5 position of the pentenone ring and the methylene position of the C4 acyl group. Photochemical isomerization with a 400 nm blue LED source provided stereospecific formation of deuterated trans-isohumulones in 36-82% yield with greater than 95% incorporation of deuterium in the C5 ring position. Oxidation of humulones with cumene hydroperoxide in basic D2O gave isohumulinones with partial 55-73% incorporation of deuterium due to keto-enol isomerization of the methylene substituent of the C4 acyl group. Structural identity of the deuterated products was determined by a combination of negative mode electrospray mass spectrometry (MS-ESI-) and 2D heteronuclear proton-carbon HMQC nmr analysis.