Transition-metal
catalyzed reactions that are able to construct
complex aliphatic amines from simple, readily available feedstocks
have become a cornerstone of modern synthetic organic chemistry. In
light of the ever-increasing importance of aliphatic amines across
the range of chemical sciences, this review aims to provide a concise
overview of modern transition-metal catalyzed approaches to alkylamine
synthesis and their functionalization. Selected examples of amine
bond forming reactions include: (a) hydroamination and hydroaminoalkylation,
(b) transition-metal catalyzed C(sp3)–H functionalization,
and (c) transition-metal catalyzed visible-light-mediated light photoredox
catalysis.
We report a general visible-light-mediated strategy that enables the construction of complex C(sp 3)rich N-heterospirocycles from feedstock aliphatic ketones and aldehydes with a broad selection of alkene-containing secondary amines. Key to the success of this approach was the utilization of a highly reducing Ir-photocatalyst and orchestration of the intrinsic reactivities of 1,4-cyclohexadiene and Hantzsch ester. This methodology provides streamlined access to complex C(sp 3)-rich N-heterospirocycles displaying structural and functional features relevant to fragment-based lead identification programs.
A new application of Pd-catalysed allylation is reported that enables the synthesis of a range of branched sp -functionalised sulfonamides, a compound class for which few reported methods exist. By reacting benzyl sulfonamides with allylic acetates in the presence of Pd catalysts and base at room temperature, direct allylation was efficiently performed, yielding products that are analogues of structural motifs seen in biologically active small molecules. The reaction was performed under mild conditions and could be applied to nanomolar sigma-receptor binders, thus enabling a late-stage functionalisation and efficient expansion of drug-like chemical space.
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