Enol thioethers from aldehydes

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

Several compounds were examined for concentration-dependent inactivation of AdoHcy hydrolase from beef liver (Table 1), and candidates were selected for evaluation of time-dependent inactivation (Table 2). The 5 -a-fluoro thioethers 10a, 10b, and 10c were quite potent inactivators. However, it was observed that lOa-c were unstable in the buffer test solutions, and other compounds were formed (HPLC) soon after the samples were dissolved. H NMR peaks at 6 9.8 and -11.7 (DMSO-de) were present after 10a was allowed to stand in aqueous solution. The first peak was stable upon addition of D2O, but the second peak at 5 11.7 rapidly disappeared upon D2O exchange. This is consistent with chemical hydrolysis of the 5 -a-fluoro thioethers 10 to give the epimoic 4 -carbaldehyde 28, hydroxy enol etho 29, and aldehyde dihydrate 30 products (see Scheme 4). 

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