**21. Enamine catalysis: α-hydroxylation of aldehydes and ketones**

The α-hydroxylation of carbonyl compounds is a very important class of reaction in the design of drug molecules; mostly the hydroxylation is appended in a stereoselective fashion. Conveniently it is achieved by enolizing the carbonyl, and the oxidation is done by oxidizing agents such as epoxides, OsO4, and so on. Rarely the singlet oxygen is used for this functional group introduction. In this VLPC condition, the hardships related to the α-hydroxylation reactions are tackled with ease; an amine-catalyzed enantioselective α-hydroxylation of aldehydes under photochemical condition was achieved where (L)-α-Me proline-based organocatalyst was exploited and singlet oxygen is employed instead of explosive oxidizing agents. Mechanistically the amino acid-based organocatalyst activated the aldehyde, and

**Figure 28.** *Enamine hydroxylation.*

substrate aldehydic compound reacts with a chiral enamine (organocatalyst) forming a chiral enamine intermediate; thereby the substrate is tuned to be nucleophilic in nature, and the nucleophilicity arises at the α-position to the aldehydic chromophore. Simultaneously, in the reaction medium, the photocatalyst is electronically excited by the visible light; once excited, it accepts a single electron from the chiral enamine, and the Ru [I] species then reduces the α-bromocarbonyl compound, and in this process the photocatalyst is regenerated. At the work-up the coupled product is released from the enamine with high stereoselectivity and in

*Photophysics, Photochemical and Substitution Reactions - Recent Advances*

**20. Enamine catalysis: α-benzylation of aldehydes and ketones,**

quinolines, and benzimidazoles undergo facile reaction (**Figure 27**).

α-Benzylation and α-alkylation are thematically one and the same; however, much recent advances in α-benzylation of carbonyl compounds were reported with

A variety of electron-deficient aryl and heteroaryl methylene bromides were examined as the benzylating agents, and they were coupled with a range of aldehydes bearing different functional groups efficiently with excellent enantioselectivity. The benzylation reaction proceeds via an oxidative quenching cycle, in contrast to the reductive quenching cycle operation in the α-alkylation reaction. The hybrid organocatalytic cycle and photoredox catalytic cycle are similar to the reaction of aldehydes with alkyl halides described in **Figure 11**. The Ir photocatalyst fac-Ir(ppy)3 and imidazolidinone organocatalyst generate the benzyl radical from electron-deficient benzyl halides. This benzyl radical then couples with the chiral enamine providing α-amino radical which is oxidized by the intermediate Ir(IV) species. Hydrolysis of the iminium ion releases the α-benzyl aldehyde. A range of electron-deficient heteroaromatics such as pyridines, pyrazines, pyrimidines,

good yields (**Figure 25**).

**Figure 25.** *Enamine catalysis.*

stereoselectivity (**Figure 26**).

**Figure 26.** *Enamine benzylation.*

**148**

**α-hydroxylation, β-arylation**

the α-position is ready for reactivity. Photosensitizer tetraphenylporphyrin (TPP) sensitizes <sup>3</sup> O2 to <sup>1</sup> O2 by the action of visible light, which then reacts with the substrate enamine through an ene-type reaction, forming α-hydroperoxide which is then reduced using NaBH4 to get 1,2-diols. Later this methodology was extended to cyclic ketones and yielded appreciable enantioselectivity (**Figure 28**).

of reactions under VLPC are photosynthesis mimic reactions, and the chemists

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

Among all the subdisciplines of catalysis, the newly emerged gifted child, namely, visible-light photoredox catalysis, has grown rapidly and has made a great of deal of interest in both academia and industry; in the near future, we will be

The twin catalysis comprising a chiral agent and the transition metal catalyst brought forward the asymmetric synthesis in a one-pot synthetic fashion in this neoteric protocol which portraits the highest level of creativity of synthetic chemists. Consequently, it can be construed that from the catalytic professionals, more VPLC protocols will emerge to attain pharmaceutically active ingredients through industrial manufacturing processes, especially in enantiomerically enriched forms. In terms of kinetics, not much work is done, and such research articles are expected in the pipeline; much work has to be done on the recyclability and reus-

It is interesting to note that only in this domain the methodology quickly reached to the stage of asymmetric synthesis in a rapid way, implying the success in the process development of drug molecules; subsequently, more process develop-

VLPC strategies developed by chemists in recent years portrait the esthetic taste and the design of energy-saving and environmentally compatible and benign fea-

brought the process into action at the laboratories.

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

tures in this innovative domain of organic synthesis.

witnessing the process development of drug molecules.

ability of catalytic materials including the studies on leaching.

, Shobha Waghmode<sup>2</sup> and Suresh Iyer<sup>3</sup>

2 Abasaheb Garware College, SPPU, Pune, Maharashtra, India

3 National Chemical Laboratory, Pashan, Pune, Maharashtra, India

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*

ments are expected as the industrial process.

1 Heriot-Watt University, United Kingdom

\*Address all correspondence to: s.iyer@ncl.res.in

provided the original work is properly cited.

**Author details**

Alwar Ramani<sup>1</sup>

**151**
