We acknowledge that Drs. Zoe Pikramenou and Peter Glover (University of Birmingham) first prepared and provided a sample of the nonfluorinated Er(tpip) 3 compound for initial studies, though none of the work detailed in this paper has utilized that sample.

For the efficient approach to medicinally important α-branched 3-acyltetramic acids, the key reaction of O- to C- acyl rearrangement using α-amino-acid-derived 4-O-acyltetramic acids was extensively examined in the presence of various metal salts. Use of CaCl(2) or NaI dramatically changed the results in the reaction efficiency and rapidly brought about the desired α-branched 3-acyltetramic acids in markedly improved yields. We also discuss an epimerization at C5 stereocenter under the rearrangement conditions as well as the tolerance for structural variation at C3 and C5. In addition to the preceding success in the total synthesis of new cytotoxic tetramic acid, penicillenol A(1), this methodology could be also applied to the first total synthesis of penicillenol A(2).

This article is a full account of the work exploring the potential utility of catalytic enantioselective amide allylation of various isatins using indium-based chiral catalysts. A survey of various isatin substrates and NH-containing stannylated reagents revealed that the reaction has a remarkably wide scope to result in extremely high yields and enantioselectivities (up to >99 %, 99 % ee) of variously substituted homoallylic alcohols. Several mechanistic investigations demonstrated that the substrate-reagent hydrogen-bond interaction plays a critical role in the formation of the key transition states to result in enhanced catalytic reaction. The success of this approach allowed convenient access to chiral 2-oxindoles spiro-fused to the α-methylene-γ-butyrolactone functionality and their halogenated derivatives in almost enantiopure forms, thus highlighting the general utility of this synthetic method to deliver a large variety of antineoplastic drug candidates and pharmaceutically meaningful compounds.

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