NaOH-Catalyzed Thiolysis of α,β-Epoxyketones in Water. A Key Step in the Synthesis of Target Molecules Starting from α,β-Unsaturated Ketones

NaOH (0.02−0.3 molar equiv) is an efficient catalyst for the thiolysis reactions of α,β-epoxy ketones with alkyl and aryl thiols in water. Thiolysis of 3,4-epoxyheptan-2-one (1) with thiols 2a−d has been accomplished in mild conditions (30 °C and pH 6 or 9) with complete C-α-regioselectivity and anti-stereoselectivity, and the corresponding anti-β-carbonyl-β-hydroxysulfides 3a−d have been prepared in excellent yields (95−98%). Compounds 3a−d, depending on their nature and pH conditions, have undergone dehydration, C-3 epimerization reaction, and retroaldol condensation. Dehydration of anti -3a−d has been chemoselectively carried out by in situ acidic treatment at 70 °C, giving stereoselectively the related (Z)-vinyl sulfides 4 in 89−94% overall yields. Under NaOH-catalyzed thiolysis conditions, cyclic α,β-epoxyketones 6−9 have shown C-α attack only and spontaneously dehydrated to furnish the corresponding vinyl sulfides in high yields (90−96%). The reactions of calchone oxide (10) with thiols 2b−d have exclusively resulted in the formation of β-carbonylsulfides 10b−d (82−93% yield), coming from the nucleophilic attack at the α-position and retroaldol condensation. To highlight the synthetic utility of this procedure, one-pot multisteps preparation of vinyl sulfides 7b and 7c, vinyl sulfoxides 12 and 13, and 1,5,6,7-tetrahydro-4H-1,2,3-benzotriazol-4-one (14) starting from 2-cyclohexen-1-one (11) have also been reported.