**4. Direct C**d**H arylation and alkylation of aldehydes**

alternate reaction pathways under benign reaction conditions. They have thus been used as photoredox catalysts and serve as photosensitizers in organic synthesis [5].

*Photophysics, Photochemical and Substitution Reactions - Recent Advances*

Aldehydes are prone to oxidation and amenable to attack by nucleophiles and can enolize, and as a result the dCHO functional group needs to be protected while carrying out the complex molecular architecture. Protection, de-protection, and reversing the reactivity or polarity through umpolung are the rudimentary strategies in the realm of organic synthesis. For these important tactics, recently VLPC has contributed a protection methodology, and the authors have protected the dCHO group as acetal [6]. The advantage of this protocol is that it does not employ the strong mineral, Lewis, and other acidic conditions; consequently the VLPC strategy presented by the chemists ranks as green technology. The protection was carried out using an organic dye, Eosin Y, with the use of [light-emitting diode (LED)] irradiation to promote the reaction under a milder condition. Several aldehydes were catalyzed in very high yields under household irradiation to the

The oxidation of organic compounds is being continuously explored since it is an important functional group modification, and the bench chemists are looking for environmental compatible and cost-effective methodologies for the same. By means of commercially affordable catalytic materials, several aldehydes were conveniently

catalyzed by Ru and Ir catalytic materials. The reaction is notably chemoselective and does not distress other oxidizable functional groups assembled within the molecule. Among the photosensitizers studied, Ir(dFppy)3 was the most efficient giving 99% yield of product from p-anisaldehyde. A wide range of aldehydes was studied with

this catalyst and efficaciously oxidized under visible light [7] (**Figure 4**).

[O2] is used as oxidant

**2. Photoacetalization**

corresponding acetals (**Figure 3**).

**3. Photo-oxidation of aldehydes**

*Photocatalytic synthesis of acetals from aldehydes.*

**Figure 3.**

**Figure 4.**

**134**

*Photocatalytic oxidation of aldehydes [7].*

converted into their respective carboxylic acids where the <sup>1</sup>

Direct and catalytic CdH activation or functionalization comprising of arylation, alkenylation, alkylation, allylation, and annulation reaction is an important field in the synthetic organic chemistry in the manufacture and the process development of pharmacologically and biologically active ingredients. Knowing the importance of CdH activation, direct arylation of aldehydes has been achieved in a synergistic manner, where nickel catalyst was employed in combination with VLPC system. In this outstanding redox system, a hydrogen atom transfer (HAT) was achieved on the reactions in between commercially available aldehydes and aryl and alkyl bromides under milder conditions; it is interesting to note that the yields are excellent [9] (**Figure 5**).

**Figure 5.** *Direct C*d*H arylation and alkylation of aldehydes [9].*

The mechanism is based on the photoexcitation of the Ir photocatalyst which gives rise to the highly oxidizing species Ir\* Ir[dF(CF3)ppy]2(dtbbpy) which oxidizes quinuclidine to form a cation radical. This radical cation then engages in a HAT event with any aldehyde to generate the acyl radical. Simultaneously oxidative addition of aryl bromide to LnNi (0) generates the aryl-Ni (II) species which is intercepted by the acyl radical to form the acyl-Ni complex. Both the Ni and the Ir photoredox catalysts then turn over in a critical reductive elimination step to the desired ketone product while regenerating the Ir and Ni catalysts. It is interesting to note that using this protocol, a pharmacologically active ingredient, namely, haloperidol, a typical antipsychotic drug, was synthesized [9] (**Figure 6**).

**Figure 6.** *Synthesis of haloperidol.*

A two-step synthesis of haloperidol was achieved by this photoredox methodology. 1,4-Chlorobutanal was merged with 1-bromo-4-fluorobenzene using the

photoredox protocol to yield the ketone in high yield. Further exposure of this to the piperidine nucleophile thus gave haloperidol in short steps.

borrowing tendency, and chirality induction through chiral imidazolidinones or prolinols with a thiophenol where the iridium catalyst transfers the activation of molecules by means of light energy (λ). The α-alkylation is carried out both by inter- and intramolecularly where the alkenes are alkylated at the α-position to the aldehyde functional group to furnish cyclic and acyclic products. The process is atom economical with a stereoselective process, allowing the production of valueadded molecules from feedstock chemicals in a single step while consuming only

*Visible-Light Photocatalysis of Aldehyde and Carbonyl Functionalities, an Innovative Domain*

The mechanistic pathway is based on the excitation of Ir complex, and simultaneously the chiral reagent adds to the aldehyde compound through elimination of water and forms an enamine. The excited iridium complex oxidizes the enamine present in the reaction medium through a single-electron transfer mechanism; thus formed enaminyl radical adds to the alkene substrate producing a carbon radical which is finally trapped by the hydrogen atom transfer catalyst. During the workup procedure, the iminium ion is hydrolyzed to get the enantiomerically enriched product, and the organocatalyst is regenerated. Finally the reduction of the thiyl radical by the Ir(I) species regenerates the thiol catalyst as well as the Ir(III) catalyst

With the success in the α-alkylation protocol, its intramolecular version also achieved where an intramolecular cyclization with tethered alkenes was first attempted to determine the feasibility of enantioselective ring formation reaction. Interestingly, carbocycles and heterocycles were synthesized with high yield and enantiocontrol. Tosamide- or carbamate-protected N-tethered aldehydic alkenes gave rise to the corresponding piperidines, ether-linked systems provided transsubstituted tetrahydropyrans, and carbocycles were also attained. Pyrrolidines were also formed as well as seven-membered rings such as azepanes or cycloheptanes. High stereocontrol was obtained with trisubstituted alkenes, and where multiple alkenes were available, only proximal alkenes reacted to provide the corresponding

Following this successful reaction, intermolecular reactions with styrene was attempted. A variety of substituted aldehydes provided the alkylated products in high yields and selectivity. Terminal alkenes were suitable substrates though

**6. Enantioselective α-trifluoromethylation and α-perfluoroalkylation**

The fluorinated hydrocarbons possess unique physical properties and are so useful in dyes, polymers, agrochemicals, and drugs. In pharmaceuticals the

perfluoroalkylated compounds which impart valuable physiological properties that enhance binding properties elevate lipophilicity and/or improved metabolic stability. The enantioselective incorporation of the CF3 and perfluoroalkyl groups has thus been a challenging task for the synthetic chemists, and the enantioselective α-alkyl trifluoromethylation of ketones and aldehydes has been elusive. First the enantioselective and organocatalytic α-trifluoromethylation and α-perfluoroalkylation of aldehydes have been successfully achieved using a commercially available iridium photocatalyst and imidazolidinone catalyst. MacMillan et al. describe the enantioselective trifluoromethylation of aldehydes via the successful merger of enamine and photoredox catalysis [11]. Their reaction is based on the property of electrophilic radicals to combine with facially biased enamine intermediates (derived from aldehydes and chiral amines). The radicals are derived from the reduction of alkyl halides by a photoredox catalyst (Ir(ppy)2(dtbbpy)). A broad

1,1-disubstituted alkenes reacted with moderate efficiency.

one photon [10].

cyclic molecule.

**of aldehydes**

**137**

to complete the redox cycle.

*DOI: http://dx.doi.org/10.5772/intechopen.92372*
