Selective and Catalytic Hydrocarboxylation of Enamides and Imines with CO₂ to Generate α,α‐Disubstituted α‐Amino Acids

Abstract

The first catalytic hydrocarboxylation of enamides and imines with CO2 to generate valuable α,α‐disubstituted α‐amino acids is reported. Notably, excellent chemo‐ and regio‐selectivity are achieved, significantly different from previous reports on β‐carboxylation of enamides, homocoupling or reduction of imines. Moreover, this transition‐metal‐free procedure exhibits low loading of an inexpensive catalyst, easily available substrates, mild reaction conditions, high efficiency, facile scalability and easy product derivatization, providing great potential for application in organic synthesis, pharmaceutical chemistry, and biochemistry.

Reductive dearomative arylcarboxylation of indoles with CO2 via visible-light photoredox catalysis

“…Then, the generated [ArBr] •− radical anion undergoes fragmentation to release a bromide anion and an aryl radical II 56,57 , which undergoes facile intramolecular radical addition to the C2-C3 double bond of indole to afford the benzylic radical III. The following SET with 4CzIPN •− delivers the carbon anion intermediate IV 58,59 , which could undergo nucleophilic addition to CO 2 [60][61][62][63] . Following protonation provides the dearomative arylcarboxylation product 2.…”

Syntheses of α‐Amino Acids by Using CO2 as a C1 Source

“…The synthesis of a-aminoa cids from enamines and imines under visible-light irradiation (with ab lue LED) was demonstrated by Yu and co-workersi n2 018 (Scheme 21). [23] In this case, 4CzIPN and iPr 2 NEt were employed as ap hotoredox catalyst and sacrificial reductant,r espectively. Thus, the corresponding a-di-and monosubstituted a-amino acids were obtained in high yields at room temperature.…”

“…Visible-light-driven synthesis of a-amino acids by Yu and coworkers. [23] LED = light-emitting diode. sunlight, and the a-amino acid/cyclohexylamine salt was obtained in 87 %y ield, withoute sterification by using TMSCHN 2 .…”

Photoredox-Catalyzed Enantioselective α-Deuteration of Azaarenes with D2O

“…Following our discovery, we explored the possibility of using this powerful strategy to generate α-radicals of azaarenes from α-halo-azaarenes. Notably, the ability of the subsequent process to cause protonation-like deuteration with D 2 O (Maji et al., 2010, Fan et al., 2018, Ju et al., 2018, Liao et al., 2018) but not hydrogen atom transfer (HAT) (Hironaka et al., 1984, Narayanam et al., 2009, Neumann et al., 2011) is crucial in the production of deuterated stereocenters. Meanwhile, to achieve high D incorporation, excess D 2 O might be utilized to compete with the H + from the sacrificial reductant and reaction environment, but this excess reagent would pose a formidable challenge for chiral Brønsted acid catalysis, a promising platform for derivatizing azaarene-based substrates (Yin et al., 2018, Hepburn and Melchiorre, 2016, Proctor et al., 2018, Xu et al., 2018).…”