SYNTHESIS0039-78811437-210X © Georg Thieme Verlag Stuttgart · New York 2020, 52, 2299–2310 short review 2299 en Syn thesis A. Yoshimura et al. Short Review Synthesis of Oxazoline and Oxazole Derivatives by Hypervalent- Iodine-Mediated Oxidative Cycloaddition Reactions Akira Yoshimura*a‡ 0000-0002-2577-397X N N O Akio Saito*b‡ 0000-0002-8291-2059 Mekhman S. Yusubovc 0000-0001-9233-1824 Substrates R O R Oxazoline Isoxazoline a Viktor V. Zhdankin* 0000-0002-0315-8861 ArI(III) N N O R O R a Department of Chemistry and Biochemistry, University of Oxazole Isoxazole Minnesota Duluth, Minnesota 55812, USA [email protected] [email protected] b Division of Applied Chemistry, Institute of Engineering, Tokyo University of Agriculture and Technology, 2-23-16 Naka-cho, Koganei, Tokyo 184-8588, Japan [email protected] c Research School of Chemistry and Applied Biomedical Scienc- es, The Tomsk Polytechnic University, 634050 Tomsk, Russian Federation ‡ Akira Yoshimura and Akio Saito contributed equally to this work. Received: 08.03.2020 ring, such as oxazolines, oxazoles, isoxazolines, and isoxaz- Accepted after revision: 15.04.2020 oles, are particularly important in life-saving drugs, bioac- Published online: 18.05.2020 DOI: 10.1055/s-0040-1707122; Art ID: ss-2020-m0131-sr tive natural compounds, products of the pharmaceutical in- dustry, synthetic building blocks, and as metal catalyst li- Abstract Organohypervalent iodine reagents are widely used for the gands.10–12,14,16,24–29 Therefore, the reactions forming these preparation of various oxazolines, oxazoles, isoxazolines, and isoxazoles. heterocyclic rings and those introducing functional groups In the formation of these heterocyclic compounds, hypervalent iodine species can serve as the activating reagents for various substrates, as into these rings represent a hot topic, and numerous im- well as the heteroatom donor reagents. In recent research, both chemi- portant synthetic procedures based on these reactions have cal and electrochemical approaches toward generation of hypervalent been developed. The known procedures often have serious iodine species have been utilized. The in situ generated active species drawbacks, such as harsh reaction conditions, long reaction can react with appropriate substrates to give the corresponding hetero- cyclic products. In this short review, we summarize the hypervalent- times, limited substrate scope, or poor yields. In particular, numerous synthetic procedures utilizing metal reagents iodine-mediated preparation of oxazolines, oxazoles, isoxazolines, and Downloaded by: University of Minnesota - Twin Cities. Copyrighted material. isoxazoles starting from various substrates. have been developed for efficient and mild syntheses of ox- 1 Introduction azoline and oxazole derivatives.10–12,14,16,23–28,30 However, 2 Synthesis of Oxazolines some of the metal reagents are expensive, toxic, and rare; 3 Synthesis of Oxazoles 4 Synthesis of Isoxazolines therefore, new synthetic methodologies under metal-free 5 Synthesis of Isoxazoles and mild conditions have been extensively studied. 6 Conclusion Organohypervalent iodine compounds are known as non-toxic and environmentally friendly reagents that are Key words hypervalent iodine, oxidative cyclization, oxidative cyclo- utilized in many green and sustainable organic reactions.31– addition, oxazoles, oxazolines, isoxazoles, isoxazolines 33 The reactivity pattern of hypervalent iodine compounds is similar to that of transition-metal reagents.34–40 There- 1 Introduction fore, hypervalent iodine compounds have found wide appli- cation as efficient oxidative reagents and ligand transfer re- Heterocyclic structural blocks can be found in various agents in many reactions.41–49 In fact, numerous oxidative biologically active natural and non-natural products and reactions, benzyne-mediated reactions, and new bond- are widely employed in the synthesis of pharmaceuticals, forming reactions, such as carbon–carbon, carbon–hetero- agrochemicals, dyes, and polymeric materials.1–8 Numerous atom, or hetero–heteroatom bonds, have been accom- reviews and books on the synthesis and properties of het- plished using hypervalent iodine reagents under metal-free erocyclic compounds have been published.9–23 Five-mem- conditions. In particular, these reagents have been used for bered heterocycles with nitrogen and oxygen atoms in the various ring construction reactions. Numerous classes of heterocyclic compounds have been prepared under mild © 2020. Thieme. All rights reserved. Synthesis 2020, 52, 2299–2310 Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany 2300 Syn thesis A. Yoshimura et al. Short Review oles 4 (Figure 1), starting from various substrates using hy- pervalent iodine species are summarized, and recent devel- opments in chemical and electrochemical synthetic procedures toward these heterocycles are discussed. N N NO NO R O R O R R 1 2 3 4 Oxazoline Oxazole Isoxazoline Isoxazole Akira Yoshimura (left) was born in Osaka (Japan) and completed his M.S. degree in 2007 and his Ph.D. in 2010, both from Tokushima Uni- Figure 1 Important azole derivatives versity, under the supervision of Professor Masahito Ochiai. During 2010–2015 he carried his postdoctoral research with Professor Viktor V. Zhdankin at the University of Minnesota Duluth. In 2016–2017 he 2 Synthesis of Oxazolines worked as a Visiting Research Assistant Professor at the Southern Meth- odist University (Dallas, USA). Since 2019 he has been a Researcher 5 at The oxazoline nucleus is present in many heterocyclic the University of Minnesota Duluth. His research interests are directed toward the synthetic and mechanistic organic chemistry of hypervalent compounds that have found important applications in me- main-group elements and heterocyclic chemistry. He has published dicinal and materials chemistry.14,51,53,54 Numerous synthet- over 60 research papers, mainly related to the chemistry of hypervalent ic strategies for the construction of the oxazoline ring have iodine and bromine. been explored. Particularly important are synthetic Akio Saito (second left) received his M.S. (1999) and Ph.D. (2003) de- approaches using hypervalent iodine reagents, such as (di- grees from the Tokyo University of Pharmacy and Life Sciences. In acetoxyiodo)arenes,55–65 iodosylarenes,66 (difluoroiodo)- 2001, he joined Professor Takeo Taguchi’s group as a research associate arenes,67 in situ generated iodine(III) species,68–73 or iodoni- at the same university. From 2005, he worked as an assistant professor 74,75 with Professor Yuji Hanzawa at the Showa Pharmaceutical University. In um ylides. This section covers synthetic methodologies 2012, he moved to his present position as an Associate Professor at the for the preparation of various oxazoline derivatives from Tokyo University of Agriculture and Technology. appropriate substrates using hypervalent iodine species. Mekhman S. Yusubov (second right) was born in Georgia. His M.S. The reactions of N-allylamides or N-propargylamides (1985), Ph.D. (1991), and Doctor of Chemical Sciences (1998) degrees with hypervalent iodine species results in an oxidative cy- were earned at Tomsk Polytechnic University in the laboratory of Pro- clization leading to oxazolines with various substituents. fessor Victor D. Filimonov. He is currently a professor at Tomsk Poly- For example, Harned’s group reported the oxidative cycliza- technic University. Since 1994 he has been involved in intense tion reaction of N-allylamides 5 using (diacetoxyiodo)ben- international collaborative research programs with leading research lab- oratories in South Korea, Germany, and the United Kingdom. In 2004 he zene in the presence of BF3·Et2O and acetic acid to give the started joint research in the area of hypervalent iodine chemistry with respective oxazoline compounds 6 in moderate to good Professor Viktor V. Zhdankin at the University of Minnesota Duluth. His yields (Scheme 1).55 The cyclization of chiral N-allylamides main research interests are in the fields of the chemistry of natural afforded the corresponding oxazolines in good yields and products and hypervalent iodine reagents. Professor Yusubov has pub- diastereoselectivities. lished over 100 scientific papers. Downloaded by: University of Minnesota - Twin Cities. Copyrighted material. Viktor V. Zhdankin (right) was born in Ekaterinburg, Russian Federa- PhI(OAc)2 (1.2 equiv) O R2 BF ·Et O (1.2 equiv) OAc tion. His M.S. (1978), Ph.D. (1981), and Doctor of Chemical Sciences 3 2 O AcOH (10 equiv) (1986) degrees were earned at Moscow State University. He moved to 1 R N R1 R2 the University of Utah in 1990, where he worked for three years as an H CH2Cl2, rt, 2–5.5 h N 5 6 Instructor of Organic Chemistry and Senior Research Associate with 1 Professor Peter J. Stang. In 1993, he joined the faculty of the University R = Ph, 2-O2NC6H4, 4-MeOC6H4, Me, 24–85% of Minnesota Duluth, where he is currently a professor of chemistry. He t-Bu, (E)-PhCH=CH–, etc. has published about 300 research papers, has given over a hundred re- R2 = H, i-Pr search presentations in many countries, has edited several books, and Scheme 1 Oxidative cyclization of N-allylamides 5 co-authored the Handbook of Heterocyclic Chemistry (3rd Edition, 2010) with Professors A. R. Katritzky, C. A. Ramsden, and J. A. Joule, and au- thored a book on Hypervalent Iodine Chemistry (Wiley, 2013). His main A similar (diacetoxyiodo)benzene-mediated cyclization research interests are in the areas of synthetic and mechanistic organic of N-allylamides