oa Editorial [Hot topic: Recent Advances in Cycloaddition Reactions in Natural Product Synthesis (Guest Editor: Jetze J. Tepe)]

With increasing demands on atom economy, reaction efficiency, stereoselectivity, streamlined total syntheses, as well as product diversity, new developments in cycloaddition reactions are excelling at an ever increasing pace. Cycloaddition reactions are an efficient means to install multiple stereocenters and rapidly construct core skeletal structures of complex products. It is therefore not surprising that cycloaddition reactions have found great use in the efficient assembly of numerous diverse natural products. This Hot Topic Issue highlights some of the more recent, creative and elegant applications of dipolar cycloadditions in natural product synthesis. The four review articles selected for this Hot Topic Issue are devoted to the recent advances in cycloaddition reactions and their applications as key reactions in the total synthesis of a diverse set of natural products. i) Burrell and Coldham describe the total syntheses of multiple diverse natural products using ylide 1,3-dipoles in intramolecular cycloaddition reactions with π-systems. This comprehensive review discusses the application of azomethine ylides, carbonyl ylides, nitrones and nitronates, nitrooxides and azides in the total syntheses of over thirty different classes of natural products. ii) France and Phun review the use Rh(II) catalyzed 1,3-dipolar cycloadditions of carbonyl ylides as a powerful method to generate mono-and polycyclic heterocycles in an enantioselective fashion. The tandem Rh(II)- catalyzed carbonyl ylide/1,3-dipolar cycloaddition reactions have shown tremendous utility in the asymmetric synthesis of various natural products. iii) Garner and Kaniskan describe the use of the asymmetric [C+NC+CC] coupling reaction and its elegant application in the formal total synthesis of cyanocycline A. These stereoselective multi-component azomethine ylide cycloaddition reactions produce highly functionalized pyrrolidines in a highly predictable and controlled fashion. iv) Hsung and co-workers describe the recent developments in aza-[3+3] annulations. This unique approach to bond formation provides pivotal piperidinyl heterocycles that represent a prevalent structural motif in many biologically relevant natural products. As guest editor for COS for this special issue I would like to acknowledge and thank the contributors for their efforts to provide these timely reviews.