Catalyst-Free Formal Conjugate Addition/Aldol or Mannich Multicomponent Reactions of Mixed Aliphatic Organozinc Reagents, π-Electrophiles and Michael Acceptors.

Catalyst-free multicomponent reactions of mixed alkylzinc reagents with Michael acceptors and aldehydes, ketones or activated imines are described. Primary, secondary and tertiary alkylzinc reagents, pre-generated in acetonitrile from the corresponding iodoalkanes, were used in the process, leading to the very efficient formation of a variety of ß-hydroxycarbonyl compounds. The imines showed more contrasting results, due to the direct addition of the organozinc compound to the C=N bond. Mechanistic assays involving TEMPO account for a polar instead of a radical character of the reaction.

Mixed Aliphatic Organozinc Reagents as Nonstabilized Csp3-Nucleophiles in the Multicomponent Mannich Reaction.

The use of mixed aliphatic organozinc reagents in the multicomponent Mannich reaction is described. A large variety of primary, secondary, and tertiary organozinc reagents, secondary amines and aromatic or aliphatic aldehydes could be used for the straightforward preparation of densely substituted amines. The three-component reaction could additionally be performed starting from alkyl halides under reductive (Barbier-type) conditions.

Straightforward Synthesis of Spirocyclic Tetrahydrofurans by a Reductive MCR/Iodoetherification Sequence.

A straightforward and modular sequence for the synthesis of substituted spirocyclic tetrahydrofurans is described. The strategy relies on a reductive cobalt-catalyzed three-component reaction between a cyclic ketone, an acrylate, and a vinylic bromide followed by an intramolecular iodoetherification of the resulting γ-hydroxyalkene. Some functional group interconversions allowed the preparation of more varied spirocyclic compounds.