Hydroaminomethylation of Olefins with Aminomethyltrifluoroborate by Photoredox Catalysis

Abstract

A photocatalytic hydroaminomethylation of olefins with N-protected aminomethyltrifluoroborates has been developed. This methodology provides a new strategy for the introduction of a primary aminomethyl group onto electron-deficient C=C bonds. This reaction constitutes a facile entry into synthetically useful g-aminobutyric acid (GABA) derivatives such as baclofen.

Photoredox Catalysis in Organic Chemistry

“…For example, Koike and Akita 162 along with our laboratory 38 demonstrated that photoredox-catalyzed conjugate additions of α-amino radicals could be applied toward the concise racemic syntheses of baclofen and pregabalin, respectively. In a collaboration with Eli Lilly, Stephenson demonstrated that photoredox-mediated coupling of N -methylmorpholine with pyridazine 92 provides rapid access to an intermediate in the synthesis of JAK2 inhibitor LY2784544 (Scheme 34a).…”

Silver‐Catalyzed Efficient Synthesis of Oxindoles and Pyrroloindolines via α‐Aminoalkylation of N‐Arylacrylamides with Amino Acid Derivatives

“…[1][2][3] The most studied methods for the generation of a-aminoalkyl radicals include photoredox catalyzed abstraction of the hydrogen at a-carbon of the nitrogen atom of alkyl amines 1 and the desilylation of a-silylamines. In this context, various protocols have been developed, particularly for the formation and addition of a-aminoalkyl radicals pecies.…”

“…In this context, various protocols have been developed, particularly for the formation and addition of a-aminoalkyl radicals pecies. [3] On the other hand, the silver-catalyzed decarboxylative generation of alkyl radicals from aliphatic carboxylic acids has been extensively reported as ag eneral method for the synthesis of alkyl compounds. [2] Several examples using the deborylation of a-borylamines have also been reported.…”

α‐Arylation/Heteroarylation of Chiral α‐Aminomethyltrifluoroborates by Synergistic Iridium Photoredox/Nickel Cross‐Coupling Catalysis

“…The intermediacy of α-amino radicals to elaborate aryl- and heteroaryl substructures has recently been demonstrated in photoredox catalysis [6,25,28,36] from both unfunctionalized amines (toward the preparation of JAK2 inhibitor LY2784544), [6] and those with the TMS [35,37,38] and CO 2 H [2,39] activating groups (Scheme 1). …”