Key words
α-imino ketones -
C-acylimines - ambiphilic reactivity - cycloadditions - annulations - asymmetric synthesis
Sustainable synthesis is one of the key concerns for synthetic organic chemists. Amongst
several factors, initiating chemical synthesis from readily available and inexpensive
starting materials through one-pot, multicomponent approaches contribute significantly
to sustainable synthesis. Such reactions are particularly important in the chemical
industry because they facilitate scale-up and large-scale synthesis with relative
ease. α-Imino ketones, also known as C-acylimines, are key building blocks in organic synthesis.
Traditionally, α-imino ketones are synthesized from inexpensive α-keto aldehydes or
1,2-diketones and amines through removal of water via simple mixing under various
conditions. Additionally, several other methods have been developed, such as NHC-catalyzed
aroylation of aromatic aldehydes with imidoyl chlorides[1] and nitrosobenzene-mediated carbon–carbon bond cleavage using LHMDS.[2] However, in this graphical review, we will focus on the synthetic applications of
α-imino ketones rather than their synthesis. It is worth noting that the structure
of α-imino ketones resemble those of certain natural biological substances due to
the presence of the imino group (–C=N–), which allows these substrates to be converted
into biologically relevant β-amino alcohols in a one-pot process.[3] The structure of α-imino ketones includes both imine and ketone functionalities
in conjugation, resembling a conjugated ketone where the β-carbon of a 1,4-enone is
replaced with nitrogen in α-imino ketones. This modification results in completely
different reactivity for C-acylimines; while 1,4-enones can undergo both 1,2-addition and 1,4-conjugate addition
depending on the reaction conditions, C-acylimines cannot participate in conjugate addition, though direct 1,2-addition is
possible. More intriguingly, the α-carbon in these substrates demonstrates umpolung
reactivity. Thus, they exhibit ambiphilic reactivity, with the two heteroatoms (oxygen
and nitrogen) displaying nucleophilic characteristics and the two carbons (the carbonyl
carbon and the imine carbon) showing electrophilic properties. Due to these unique
reactivity patterns, numerous synthetic groups have utilized α-imino ketones as key
precursors for constructing aza-(hetero)cyclic compounds.
Figure 1 Cycloaddition reactions of α-imino ketones (part 1)[1]
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Figure 2 Cycloaddition reactions of α-imino ketones (part 2)[5`]
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Figure 3 Cyclization reactions of α-imino ketones[6`]
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Figure 4 Formation of C–C bonds using α-imino ketones[7`]
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Figure 5 Other reactions of α-imino ketones[8`]
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