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

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

photoredox protocol to yield the ketone in high yield. Further exposure of this to the

**5. C**d**C bond formation enhanced by VPLC and alkylation of aldehydes**

The α-alkylation of carbonyl compounds is a routine affair for synthetic chemists both for making substituents and also to synthesize pharmaceutically active ingredients (**Figures 7** and **8**). In the case of α-alkylation of aldehydes, the acidic methylenic (CH2) hydrogen atoms are acidic in nature, and they can be removed; as a result an enol form is produced which directs the alkylating agents attached to the α-alkylation. A skillful execution of three catalytic materials together in a synergistic fashion enables an enantiomeric α-alkylation of aldehydes; mechanistically, the triple catalytic process is sequenced to deliver a hydrogen atom transfer, electron

piperidine nucleophile thus gave haloperidol in short steps.

*Photophysics, Photochemical and Substitution Reactions - Recent Advances*

**through alkenes as alkylating agents**

**Figure 7.**

**Figure 8.**

**136**

*Intramolecular alkylation.*

*Intermolecular alkylation with alkenes.*

**Figure 9.** *α-Trifluoromethylation of aldehydes [12].*

range of perfluoroalkyl halides were found to participate in the enantioselective alkylation reaction. N-perfluoroalkyl substrates of varying chain length undergo successfully reductive radical formation and enamine addition with high yields and enantioselectivity (**Figure 9**).

**Figure 10.**

**Figure 11.**

**139**

*Catalytic cycle—the direct asymmetric alkylation of aldehyde.*

*The direct asymmetric alkylation of aldehydes.*

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

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

The α-alkylation of carbonyl compounds is always an essential tool in the synthetic organic chemistry. It can be carried out both inter- and intramolecularly; the intramolecular version builds up the cyclic compounds with enhanced stereoselectivity. Among the α-alkylation reactions, of late, α-trifluoromethylation reactions are being much exploited since these compounds are of greater importance in agrochemical and pharmaceutical compounds. Iodotrifluoromethane is employed as a trifluoromethylating agent under a VLPC condition where the reaction and optical yields are highly appreciable. Mechanistically, the light excites the Ir complex, which oxidizes the enamine compound through a single-electron transfer mechanism; the enamine radical adds with the alkene substrate producing carboncentered radical; thus series of reaction provides the desired compound, and the catalyst is regenerated [12].
