An enantioselective synthesis of spiro-oxindole-based 3,4-dihydropyrroles via a Michael/cyclization cascade of 3-aminooxindoles with 2-enoylpyridines.

An organocatalytic and highly diastereo- and enantioselective reaction of 3-aminooxindoles with 2-enoylpyridines for the synthesis of chiral spiro[pyrrolidin-3,2'-oxindole] derivatives has been achieved. With the cinchonidine-based thiourea catalyst, the asymmetric Michael/cyclization reaction sequence of 3-aminooxindoles with 2-enoylpyridines followed by the dehydration and deprotection with concentrated hydrochloric acid provided a wide range of chiral 3',4'-dihydrospiro[indoline-3,2'-pyrrol]-2-ones, bearing two adjacent tri- and tetrasubstituted stereocenters, in moderate to good yields with overall excellent stereoselectivities. The synthetic application of this methodology was presented by the scale-up experiment and transformation of product 5a into the spiro-oxindole-based pyrrolidine 6.

Synthesis of 2,3'-spirobi[indolin]-2-ones enabled by a tandem nucleophilic benzylation/C(sp)-N cross-coupling reaction sequence.

An efficient complementary strategy for the construction of spiro[pyrrolidin-3,2'-oxindole] derivatives has been described. With the sequential nucleophilic benzylation and copper-catalyzed intramolecular C(sp)-N cross-coupling reaction of 3-aminooxindoles with 2-bromobenzyl bromides, a wide range of 2,3'-spirobi[indolin]-2-ones were smoothly obtained in moderate to good yields. A plausible catalytic cycle for this tandem reaction process was proposed based on the control experiments.