Enantioconvergent Cu-catalysed N-alkylation of aliphatic amines

Copper-Catalyzed Enantioconvergent Radical C(sp3)–N Cross-Coupling of Activated Racemic Alkyl Halides with (Hetero)aromatic Amines under Ambient Conditions

“…These observations together favor the formation of alkyl radical species from alkyl halides via a single-electron reduction process with the L* Cu­(I)-amido complex. Of particular note, the strategy was mechanistically distinct from our reported N -alkylation of aliphatic amines, which proceeds via a direct outer-sphere amine attack of the Cu­(III) intermediate …”

“…Accordingly, a series of enantioconvergent radical cross-coupling reactions have been established . In particular, we have recently disclosed an enantioconvergent N -alkylation of aliphatic amines to provide α-chiral aliphatic amines via a mechanistic outer-sphere amine attack of the Cu­(III) intermediate . Given the importance of chiral N -alkyl (hetero)­aromatic amines, we were then intrigued to explore an enantioconvergent radical C­(sp 3 )–N coupling of (hetero)­aromatic amines.…”

“…Since the acidity of aromatic amines is stronger than that of aliphatic amines, we theorized that the Cu­(I)-amino complex with aromatic amines should be easily formed. As such, we assumed that the transformation of aromatic amines might proceed in a mechanistically different strategy from that of aliphatic amines . Thus, the in situ-generated L* Cu­(I)-amido complex would reduce racemic alkyl halides to generate the prochiral alkyl radical.…”

Enantioselective Formation of α-Amino Acid Derivatives via [2,3]-Sigmatropic Rearrangement of N-Acyl Iminosulfinamides

“…Chiral α-amino acids and their derivatives are in great demand in chemistry, life sciences, and biotechnology, thereby leading to extensive efforts to synthesize them . Enantioselective introduction of an amino group at the α-position of carboxylic acid derivatives is one of the most important transformations to access chiral α-amino acid derivatives and is achieved mainly through asymmetric α-amination involving polar or radical intermediates. In contrast, we are aware of only two approaches based on [2,3]-sigmatropic rearrangement. , In the first approach, chemoselective electrophilic amide activation is followed by attack from the oxygen atom of sulfinamides to produce amino-vinyloxy-sulfonium intermediates that undergo [2,3]-sigmatropic rearrangement and subsequent cleavage of the S–N bond (Scheme a) .…”

Cu-Catalyzed C(sp3) Amination of Unactivated Secondary Alkyl Iodides Promoted by Diaryliodonium Salts

“…In recent years, copper catalysts have offered innovative pathways for accessing sp 3 architectures . While the low reducing ability of Cu­(I) species might a priori prevent their utilization as catalysts for enabling sp 3 carbon halide bond cleavage in alkyl halides (bottom left panel in Scheme ), pioneering work from Fu and Peters showed that photoexcitation of transient amido-Cu­(I) species allows access to highly reducing Cu­(I) entities that enable single-electron transfer (SET) reduction processes at the alkyl halide terminus .…”