• Sajal Sarkar

In 1967, Oyo Mitsunobu published a significant study on the synthesis of esters from alcohols and carboxylic acids utilizing equimolar quantities of two auxiliary reagents: diethyl azodicarboxylate (DEAD) and triphenylphosphine1. Throughout the reaction, the azo species is reduced to a hydrazine derivative, while the phosphine undergoes oxidation to form phosphine oxide as a by-product. A diverse array of nucleophiles or pronucleophiles with a pKa of 15 or lower, ideally below 11, can participate in the ‘conventional’ Mitsunobu reaction2. Suitable pronucleophiles include carboxylic acids, phenols, imides, purine and pyrimidine bases, as well as related heterocycles. Additionally, hydrazoic acid (HN3), thiocarboxylic acids, thiols, fluorinated alcohols, and hydroxamates are also effective3. Intramolecular Mitsunobu reaction afforded lactones, lactams, cyclic ethers, amines and macrocyclic frameworks4–18. The Mitsunobu reaction is a highly stereoselective process and takes place with inversion of the stereochemical configuration of the starting chiral alcohols19–31. The Mitsunobu esterification route offers significant advantages over other strategies. Following the esterification process, hydrolysis of the product yields the inverted alcohol with high enantiomeric purity. The Mitsunobu reaction is typically performed under mild and nearly neutral conditions, usually within a temperature range of 0 °C to 25 °C. Common solvents used in this reaction include tetrahydrofuran, toluene, diethyl ether, acetonitrile, DMF, and dichloromethane20,32–47. The applicability of the Mitsunobu reaction is hindered by the challenges associated with separating by-products, such as phosphine oxide and hydrazine derivatives. Despite this, it remains a compelling area of research within the API industry. Numerous emerging strategies have been reported in the literature that enhance the purity of isolated products in Mitsunobu reactions48,49. The Mitsunobu reaction is an invaluable tool for synthesizing a diverse array of functional groups in drug discovery. Numerous specialized review articles have been published to provide a deeper understanding of this reaction. This micro review focuses on the latest advancements and applications of the Mitsunobu reaction within the field of medicinal chemistry.

An Overview of the Mitsunobu Reaction in Pharmaceutical Synthesis

" An Overview of the Mitsunobu Reaction in Pharmaceutical Synthesis", International Journal of Emerging Technologies and Innovative Research (www.jetir.org), ISSN:2349-5162, Vol.6, Issue 5, page no.316-329, May-2019, Available :http://www.jetir.org/papers/JETIR1905Z36.pdf

" An Overview of the Mitsunobu Reaction in Pharmaceutical Synthesis", International Journal of Emerging Technologies and Innovative Research (www.jetir.org | UGC and issn Approved), ISSN:2349-5162, Vol.6, Issue 5, page no. pp316-329, May-2019, Available at : http://www.jetir.org/papers/JETIR1905Z36.pdf