**15. Enamine, direct β-alkylation**

antiemetic, and antimigrainic activities, and hence developing a working technology for the syntheses of piperazine analogues is very important to arrive at structural activity relationship. To arrive at an array of piperazines, recently a research article is reported that utilizes silicon-based reagents, and they denote this as silicon amine protocol (SLAP); in this process a variety of aromatic, heteroaromatic, and aliphatic aldehydes and ketones were employed to produce an array of piperazines using iridium-based photoredox catalyst (Ir[(ppy)2dtbbpy]PF6) and blue light radiation. The products obtained do not have any trace metal impurities since this protocol is tin-free alternative (SnAP—tin amine protocol). The reaction conditions enforced is mild and tolerates unprotected functional groups and steric hindrance and very importantly provides an access to wide array of piperazines without any

*Photophysics, Photochemical and Substitution Reactions - Recent Advances*

The direct β-functionalization of carbonyl groups is very little known. MacMillan et al. first reported the combination of organocatalysis and photoredox catalysis for the direct β-CdH arylation of carbonyl compounds using benzonitrile as aryl donor (**Figure 18**). The proposed mechanistic rationale is shown in **Figure 19** and

trace metals for the SAR studies [18].

**14. β-Arylation of aldehydes**

**Figure 18.**

**Figure 19.**

**144**

*β-Arylation of aldehydes—organocatalytic cycle.*

*β-Arylation of aldehydes.*

Saturated aldehydes can be alkylated at the beta position directly by a synergistic combination of photoredox catalysis and organocatalysis [20]. Enamine oxidation by visible-light LED provides an activated β-enaminyl radical which readily combines with a wide range of Michael acceptors to produce β-alkyl aldehydes efficiently. Both inter- and intramolecular CdH functionalizations are possible in an atom economical redox-neutral process (**Figure 20**).

**Figure 20.** *Direct β-alkylation of enamines.*

1,4-Diazabicyclo[2.2.2]octane (DABCO) as an organic base and DME as solvent were essential for the desired bond formation reaction. Thus a unique 5-πe-carbonyl activation utilizing the synergistic merger of organocatalysis and photoredox catalysis was used to accomplish the direct β-arylation of saturated ketones and aldehydes. A catalytically generated enaminyl radical formed via oxidation and βdeprotonation of an enamine and a radical anion generated by photocatalytic reduction of cyanoarene couple to form the β-carbonyl products. The generality of the activation platform was further demonstrated by a β-aldol reaction of ketones with transiently generated aryl ketyl radicals to form γ-hydroxy ketone adducts. The reaction was then further extended to intramolecular cyclization via formation of cyclic molecules through both 6-exo and 5-exo cyclizations with useful efficiencies and diastereocontrol. This proves further that the critical step does not involve radical-radical coupling (**Figure 21**).

**Figure 21.** *5πe activation, 6-exo to 5-exo.*
