Highly stereoselective [4+2] and [3+2] spiroannulations of 2-(2-oxoindolin-3-ylidene)acetic esters catalyzed by bifunctional thioureas.

A new Michael-Michael cascade reaction between 2-(2-oxoindolin-3-ylidene)acetic esters 1 and nitroenoates 2, catalyzed by bifunctional thioureas, is investigated. The combination of the two Michael reactions results in a novel and facile [4+2] or [3+2] spiroannulation process, which is characterized by the following features: 1) two carbon-carbon bonds and four stereocenters, including a quaternary spiro carbon, are formed under mild conditions; 2) an unprecedented and stereochemically defined substitution pattern on the spirocarbocyclic unit is obtained; 3) the double-bond configuration of the donor-acceptor nitroenoate 2 determines the absolute configuration of the spiro center, whereas the remaining stereocenters are formed under control of the catalyst. The effect on the final stereochemical outcome of structural variations of each starting material, catalyst, and experimental conditions is analyzed in detail. In particular, the use of specifically designed chiral nitroenoates enables diverse polyfunctional spirocyclohexane derivatives containing six consecutive stereogenic centers to be constructed. To our knowledge, this is the first asymmetric organocatalytic strategy enabling both five- and six-membered ß-nitro spirocarbocyclic oxindoles.

Photo-organocatalysis of atom-transfer radical additions to alkenes.

We have found that an organic molecule as simple as p-anisaldehyde efficiently catalyzes the intermolecular atom-transfer radical addition (ATRA) of a variety of haloalkanes onto olefins, one of the fundamental carbon-carbon bond-forming transformations in organic chemistry. The reaction requires exceptionally mild reaction conditions to proceed, as it occurs at ambient temperature and under illumination by a readily available fluorescent light bulb. Initial investigations support a mechanism whereby the aldehydic catalyst photochemically generates the reactive radical species by sensitization of the organic halides by an energy-transfer pathway.

Organocatalytic conjugate addition of nitroalkanes to 3-ylidene oxindoles: a stereocontrolled diversity oriented route to oxindole derivatives.

An efficient and highly enantioselective Michael addition of nitroalkanes to 3-ylidene oxindoles is described, mediated by thiourea-based bifunctional organocatalysts. The stereochemistry at C(α) and C(ß) centers is perfectly controlled, and the intermediate C-3 enolate is trapped with a second Michael acceptor. The developed one-pot three-component consecutive reactions generate up to four contiguous stereocenters, including the C-3 all-carbon quaternary center, in a perfectly defined configuration. The conversion of the ß-nitro oxindole into the corresponding ß-amino derivative discloses synthetically useful transformations, exploitable to generate pharmaceutically attractive molecular targets.