Synlett

Spirocyclic 3,5-difluorocyclohexa-2,5-dienones possessing a triisopropylsiloxy-containing cyclic ether appendage were synthesized by oxidative dearomatization of the corresponding phenols. By group selectivity in the nucleophilic 1,4-addition/elimination reaction, highly stereoselective formation of the spiro center was successfully achieved. This reaction might provide access to total syntheses of (+)-bisdechlorogeodin and (+)-geodin with complete control of the formation of the spirocyclic structure.

The Thorpe–Ingold effect was applied to the design of a chiral ligand of π–copper(II) catalysts for the enantioselective α-fluorination of N-acyl-3,5-dimethylpyrazoles, and also for the enantioselective Mukaiyama–Michael, Diels–Alder, and 1,3-dipolar cycloaddition reactions of N-acryloyl-3,5-dimethylpyrazoles. The use of β,β-dimethyl-β-arylalanine-type ligand gave desired products with higher enantioselectivity compared to with previously reported β-arylalanine-type ligands.

A copper-catalyzed radical difluoroalkylation of arylacetylenes with bromodifluoroamides has been developed. The reaction exhibits good functional group tolerance and allows access to a variety of substituted α-alkynyl-α,α-difluoroacetamides in moderate to good yields. The potential for scale-up reaction and products derivatization also makes this method attractive for practical applications. Preliminary mechanistic studies suggest that a radical reaction pathway might be involved in the catalytic system.

This Account summarizes the research of the group on the multicomponent reactions arena with fundamental heterocycles as substrates, using mechanistic considerations to hypothesize new processes and to rationalize results. Biomedical applications of the ensuing adducts were also envisaged, which brought about interesting discoveries.1 Introduction and Context2 The Beginnings: Unexplored Heterocyclic Substrates3 Interrupted Processes4 Multiple Multicomponent Reactions: Problem of Selectivity5 Extended Multicomponent Reactions6 Conclusions and Wishes

Cyclic polymers are of increasing interest to the synthetic and physical polymer communities due to their unique structures that lack chain ends. This topological distinction results in decreased chain entanglement, lower intrinsic viscosity, and smaller hydrodynamic radii. Many methods for the production of cyclic polymers exist, however, large-scale production of architecturally pure cyclic polymers is challenging. Ring-expansion metathesis polymerization (REMP) is an increasingly promising method to produce cyclic polymers because of the mild and scalable reaction conditions. Herein, a brief history of REMP for the synthesis of cyclic polymers with both ruthenium and non-ruthenium initiators is discussed. Even though REMP is a promising method for synthesizing cyclic polymers, state-of-the-art methods still struggle with poor molar mass control, slow polymerization rates, low conversion, and poor initiator stability. To combat these challenges, our group has developed a tethered ruthenium-benzylidene initiator, CB6, which utilizes design features from ubiquitous Grubbs-type initiators used in linear polymerizations. These structural modifications are shown to improve initiator kinetics, enhance initiator stability, and increase control over the molar mass of the resulting cyclic polymers.1 Introduction2 Ring-Expansion Metathesis Polymerization (REMP) with Ruthenium Initiators3 New Developments in Ruthenium Ring-Expansion Metathesis (REMP) Initiator Design4 Ring-Expansion Metathesis Polymerization (REMP) with Non-Ruthenium Initiators5 Conclusions

Nature has been recognized for her super capability of constructing complex molecules with remarkable efficiency and elegancy. Among nature’s versatile synthetic toolkits, Diels–Alder reaction is particularly attractive since it allows for rapid generation of molecular complexity from simple precursors. For natural products biosynthetically formed through Diels–Alder reactions, the most straightforward way to access them should build on biomimetic Diels–Alder reactions. However, the implementation of biomimetic Diels–Alder reactions in a laboratory setting may encounter considerable challenges, particularly for those suffering from complicated reactivity and selectivity issues. Indeed, the translation of a biosynthetic hypothesis into a real biomimetic synthesis entails the orchestrated combination of nature’s inspiration and chemist’s rational design. In this Account, we will briefly summarize our recent progress on the application of biomimetic Diels–Alder reactions in natural product synthesis. As shown in the discussed stories, rational manipulation of the structures of biosynthetic precursors plays a crucial role for the successful implementation of biomimetic Diels–Alder reactions.1 Introduction2 Biomimetic Synthesis of Rossinone B3 Biomimetic Synthesis of Homodimericin A4 Biomimetic Synthesis of Polycyclic and Dimeric Xanthanolides5 Biomimetic Synthesis of Periconiasins and Pericoannosins6 Biomimetic Synthesis of Merocyctochalasans7 Conclusion and Outlook

Despite recent advances in solid-state organic synthesis using ball milling, insight into the unique reactivity of solid-state substrates, which is often different from that in solution, has been poorly explored. In this study, we investigated the relationship between the reactivity and melting points of aryl halides in solid-state Suzuki–Miyaura cross-coupling reactions and the effect of reaction temperature on these processes. We found that aryl halides with high melting points showed significantly low reactivity in the solid-state cross-coupling near room temperature, but the reactions were notably accelerated by increasing the reaction temperature. Given that the reaction temperature is much lower than the melting points of these substrates, the acceleration effect is most likely ascribed to the weakening of the intermolecular interactions between the substrate molecules in the solid state. The present study provides important perspectives for the rational design of efficient solid-state organic transformations using ball milling.

The constitutional challenge of an electrostatically directed meta borylation of sterically biased and unbiased substrates is summarized in the present work. The borylation follows an electrostatic interaction between the partially positive and negative charges of the ligand and substrate, respectively. Using our developed strategy, it has been demonstrated that a wide range of challenging substrates, especially 4-substituted substrates can be borylated at the meta position with excellent selectivity. Moreover, unsubstituted substrates are also displayed excellent meta selectivity. The reaction employs bench-stable ligand, proceeds at moderate reaction temperature (40–80 °C), precluding the need to synthesize bulky and sophisticated ligand/template.

Mechanochemical synthesis of 2,5-disubstituted 1,3,4-oxadiazoles was developed as an environmentally benign alternative to conventional solvent-based methods. In the presence of triphenylphosphine and trichloroisocyanuric acid, N-acylbenzotriazoles condense with acylhydrazides leading to oxadiazoles derivatives in good to excellent yields within minutes. The approach circumvents the need for strictly anhydrous conditions, external heating, long reaction times, as well as tedious multistep procedures. A range of substrates with reactive functionalities was also well tolerated.

We explored the reactivity and substrate scope of the reactions among an alkyl isocyanide, an sp-hybridized reactant (i.e. alkyne or allene), and a carbon cage, as a new approach to functionalize fullerenes and metallofullerenes. This account summarizes the key findings in our recent published work, and some original data for the reaction involving an isocyanide, allenes, and metallofullerene Lu3N@C80.1 Introduction2 Isocyanide-Induced Fullerene/EMF Reactions with Substituted Alkynes3 Isocyanide-Induced Fullerene/EMF Reactions with Substituted Allenes4 Conclusion