Abstract
(Englisch)
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Project 1: Reaction of a-substitüted cL-isocyanoacetates with phenyl vinyl selenones in the presence of a catalytic amount of base (DBU or Et3N, 0.05-0.1 equiv) followed by addition ofp-toluenesulfonic acid (PISA, 0.1- 0.2 equiv) afforded 4,4,5-trisubstituted 1 ‚3-oxazinan-2-ones in good to excellent yields. Enantiomerically enriched heterocycles can also be prepared using Cinchona alkaloid-derived bifunctional organocatalyst for the Michael addition step. Phenylselenonyl group served as an activator for the Michael addition, a leaving group and a latent oxidant in this integrated teaction sequence. Project 2: The reaction of propargyl amines with tert-butylisonitrile in the presence of a catalytic amount of both Yb(OTf)3 and AgOTf afforded imidazoles, whereas the same reaction with primary, secondary alkylisonitriles as weil as arylisonitriles in the ptesence of three metal saits [Yb(OTf)a!AgOTf/KOTfJ resulted in the 1,3,4,5- tetrasubstituted imidazoliums in excellent yields. Both chiral amines and chiral isonitriles can be used to provide corresponding chiral heterocycles without racemization. in this multiple catalytic system, Yb(OTt)3 catalyzed the insertion of isonitnles to the N-H bond of amines, AgOTf catalyzed the 5-exo-dig cydlization of the resulting amidine nitrogen to the tethered tripie bond while KOTf promoted the salt metathesis, providing at the same time the counterion to the imidazolium. Against common knowledge, the isocyano group acted in these reactions as a polarized triple bond instead of conventional carbene-like function. Project 3: Treatment of o-nitrostyrenes with aqueous TiCl3 solution at room temperature afforded indoles via a formal reductive C(sp2)-H amination process. A tange of functions such as halides (Cl, Br), carbonyl (ester, carbamate), cyano, hydroxyl and amino groups were tolerated. From 3ü3-disubstituted o-nitrostyrenes, 2,3- disubstituted indoles were formed via a domino reduction/cyclization/migration process. Mild conditions, simple experimental procedure, ready accessibility of the starting materials and good to excellent yields characterized the present transformation. The methodology was used as a key step in a concise synthesis of rizatriptan and a formal total synthesis of aspidospermidine.
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