A New One-Pot, Four-Component Synthesis of 1,2-Amino Alcohols: TiCl₃/t-BuOOH-Mediated Radical Hydroxymethylation of Imines

Abstract

An amine, an aldehyde, and methanol can be readily assembled in one pot under very mild conditions through a free-radical multicomponent reaction by using an aqueous acidic TiCl3/t-BuOOH system to afford 1,2-amino alcohols in fair to excellent yields.

Free‐Radical Multicomponent Processes

“…The procedure mentioned above for the Strecker reaction was adapted to the Mannich-type reaction between an aldehyde, an amine, and an alcohol such as methanol (Scheme 14.30) [88]. The latter is the precursor of the nucleophilic radical (ketyl) that will add to the imine.…”

Homogeneous and heterogeneous photoredox-catalyzed hydroxymethylation of ketones and keto esters: catalyst screening, chemoselectivity and dilution effects

“…Furthermore, the addition of TiCl 4 to methanol solutions is cumbersome and it is unclear what species is catalytically active. These processes have thermal counterparts in reduced titanium-mediated chemistry, e.g., the Ti(III)/ t -BuOOH-mediated hydroxymethylation of imines [23–24]. …”

Recent Developments in Nucleophilic Radical Addition to Imines: the Key Role of Transition Metals and the New Porta Radical-Type Version of the Mannich and Strecker Reactions

“…In fact, the polarization of the C=N bond, induced by N-Ti(IV) complexation, overcomes the substituent effect and the last Very recently [22] the TiCl 3 /t-BuOOH system was employed, in methanol as a co-solvent, to promote a radical domino multicomponent reaction with a wide range of amines and aldehydes for the preparation of , -amino alcohols (Eq. In fact, the polarization of the C=N bond, induced by N-Ti(IV) complexation, overcomes the substituent effect and the last Very recently [22] the TiCl 3 /t-BuOOH system was employed, in methanol as a co-solvent, to promote a radical domino multicomponent reaction with a wide range of amines and aldehydes for the preparation of , -amino alcohols (Eq.…”