Addition of Nitronates, Enolates, Silyl Ketene Acetals and Cyanide Ion

Addition of Nitronates, Enolates, Silyl Ketene Acetals and Cyanide Ion 

The AT-acyliminium methodology has been exploited to prepare pharmacologically active molecules, e.g., GW 311616A [82] and inhibitors of the 

Hepatite Virus NS3/4A having the pyrrolidine-5,5-trans-lactam skeleton [83], starting from (R)- and (S)-methionine, respectively. The key step is the addition of the proper silyl ketene acetal to an iminium ion, e.g., that generated by treatment of the intermediate 177 with boron trifluoride, which provided the adduct 178 with better diastereoselectivity than other Lewis acids. Inhibitors of hepatitis C virus NS3/4A were efficiently prepared by a similar route from (S)-methionine [83]. The addition of indole to a chiral (z-amino iminium ion was a completely diastereoselective step in a reported synthesis of tilivalline, a natural molecule which displays strong cytotoxicity towards mouse leukemia L 1210 [84]. 

Instead, the reaction of TMS cyanide with the chiral imine prepared from racemic 2-benzoylaminocyclohexanone and (fi)-l-phenylethylamine or (S)-l-phenylethylamine in the presence of zinc chloride occurred with low stereocontrol, and the two enantiomers of fra s-l,2-diaminocyclohexane car-boxyhc acid were isolated with low yields after several steps [88]. 

All four isomers of 4-amino-4-carboxyproHne have been prepared starting from frans-4-hydroxy-L-prohne by a sequence of steps involving Bucherer- 

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