Life science
Drug discovery, Functional materials

Diastereodivergent Synthesis of 1,2-Diamines Enabled byIodine Catalysis
Department of Applied Chemistry, Graduate School of EngineeringProfessor Satoshi Minakata
Researchmap https://researchmap.jp/read0185263?lang=en

Life science

Abstract
Iodine (the world’s second-largest production), an element thatJapan is proud of, which has few resources, is utilized as a catalyst for complete stereoselective anti- and syn-1,2-diamination of
unfunctionalized carbon-carbon double bonds (alkenes). The combined use of the two potential methods provides access to all ofthe disastereomeric forms of 1,2-diamines in spite of the availabilityof E- and Z-alkenes (Fig. 1).

▍ Background & Results
The 1,2-diamine substructure is a ubiquitous structural motif thatis found in a number of natural products, biologically active compounds, ligands for metal-mediated catalysis. Among these, themethod of introducing two amino group units into a carbon-carbon
double bond (alkene) is the most direct and diverse method ofsynthesizing 1,2-diamines. From these points of view, the development of diamination of alkens has been energetically promoted
worldwide for about 10 years. However, there are many drawbacks
such as the lack of generality of raw alkenes, the peculiarity of thenitrogen unit to be introduced, and the uncontrolled stereochemistry when converting a planar alkene to a three-dimensional diamine. In order to overcome these issues, we succeeded in finding
a synthetic strategy that permits various 1,2-diamine derivatives tobe produced from unactivated alkenes. The substrates (nitrogensources)-controlled stereospecific intermolecular anti- and syn1,2-diamination was successfully achieved. Both anti- and syndiaminations could be conducted in a stereospecific manner using
this iodine catalysis, which are regarded as the catalytic aza-Prévost-Woodward reactions. The simplicity of this new method, anti1,2-diamination is one of its more attractive aspects; the starting
components nosylamide, NaOCl·5H2O and iodine catalyst neededfor the reaction are all commercially available and inexpensive.

Fig. 1 Stereospeciflc 1,2-Diamination Enabled by I2 Catelysls▍ Significance of the research and Future perspective
The 1,2-diamine skeleton is a very important partial structure
contained in anti-influenza drugs such as Tamiflu® , Relenza® andInavir® , natural products such as biotin and ligands for metal catalyst (Fig. 2). Therefore, the present methods, which can completely
control the stereochemistry of this unit, is an extremely significant
methodology for organic synthesis. In addition, this reaction does
not use a rare transition metal catalyst, and the only by-products
after the reaction are water and sodium chloride, which can contribute to a sustainable society as a manufacturing method. Amongthe currently used drugs including the above-mentioned antiinfluenza drugs, many bioactive substances having a 1,2-diamine
substructure are found. It is unclear whether this unit is needed forthe currently coveted silver bullet for COVID-19, but the development of unprecedented reactions has enabled the rapid synthesisof new substances, a group of new drug candidate compounds.

Fig. 2. Examples of Functional Materials Containing 1,2-Diamine Molety

P a t e n t
Minakata, Satoshi; Miwa, Hayato; Yamamoto, Kenya et al. Diastereodivergent Intermolecular 1,2-Diamination of Unactivated Alkenes Enabled by Iodine
Catalysis. J. Am. Chem. Soc. 2021; 143 (11): 4112-4118. doi: 10.1021/jacs.1c00228
http://www.chem.eng.osaka-u.ac.jp/~minakata-lab/https://resou.osaka-u.ac.jp/ja/research/2021/20210316_4
URL
https://www.chem-station.com/blog/2021/07/amine.html
https://www.thieme.de/statics/dokumente/thieme/final/en/dokumente/tw_chemistry/CFZ-Synform-Diastereodivergent-Intermolecular-Diamination_LitCov.pdf
K e y w o r d 1,2-diamines, iodine catalysis, stereospecificity, alkenes
Tr e a t i s e