Synlett

The exciting field of polymer mechanochemistry has made great empirical progress in discovering reactions in which a stretching force accelerates scission of strained bonds using single molecule force spectroscopy and ultrasonication experiments. Understanding why these reactions happen, i.e., the fundamental physical processes that govern coupling of macroscopic motion to chemical reactions, as well as discovering other patterns of mechanochemical reactivity require complementary techniques, which permit a much more detailed characterization of reaction mechanisms and the distribution of force in reacting molecules than are achievable in SMFS or ultrasonication. A molecular force probe allows the specific pattern of molecular strain that is responsible for localized reactions in stretched polymers to be reproduced accurately in non-polymeric substrates using molecular design rather than atomistically intractable collective motions of millions of atoms comprising macroscopic motion. In this review, we highlight the necessary features of a useful molecular force probe and describe their realization in stiff stilbene macrocycles. We describe how studying these macrocycles using classical tools of physical organic chemistry has allowed detailed characterizations of mechanochemical reactivity, explain some of the most unexpected insights enabled by these probes, and speculate how they may guide the next stage of mechanochemistry.

Organic molecules containing the trifluoromethyl (CF3) group play a vital role in pharmaceuticals, agrochemicals, and materials. New trifluoromethylation methods should encompass capabilities to address issues in efficiency, selectivity, and CF3 source all at once. Fluoroform (CF3H), an industrial byproduct, has emerged as an attractive CF3 source. The reaction profile of the [CuCF3] reagent derived from fluo­roform has surpassed its original applications in cross-coupling-type trifluoromethylation. We have discovered a host of unique copper-mediated trifluoromethylation reactions using [CuCF3] from fluoroform, especially under oxidative conditions, to deliver efficient and selective synthesis of trifluoromethylated compounds.1 Introduction2 Construction of C–CF3 Bonds for the Synthesis of Trifluoromethylated Building Blocks2.1 C(sp)–CF3 Bond Formation2.2 C(sp2)–CF3 Bond Formation2.3 C(sp3)–CF3 Bond Formation3 Domino Synthesis of Trifluoromethylated Heterocycles3.1 3-(Trifluoromethyl)indoles3.2 3-(Trifluoromethyl)benzofurans3.3 2-(Trifluoromethyl)indoles4 Trifluoromethylative Difunctionalization of Arynes4.1 Trifluoromethylation–Allylation of Arynes4.2 1,2-Bis(trifluoromethylation) of Arynes5 Pentafluoroethylation of Unactivated Alkenes6 Conclusion

A novel mononuclear ruthenium (Ru) complex bearing a PNNP-type tetradentate ligand is introduced here as a self-photosensitized catalyst for the reduction of carbon dioxide (CO2). When the pre-activation of the Ru complex by reaction with a base was carried out, an induction period of catalyst almost disappeared and the catalyst turnover numbers (TONs) over a reaction time of 144 h reached 307 and 489 for carbon monoxide (CO) and for formic acid (HCO2H), respectively. The complex has a long lifespan as a dual photosensitizer and reduction catalyst, due to the sterically bulky and structurally robust (PNNP)Ru framework. Isotope-labeling experiments under 13CO2 atmosphere indicate that CO and HCO2H were both produced from CO2.

Asymmetric organocatalysis is emerging as an elegant tool for accelerating chemical reactions and creating specific types of molecules. Chiral Brønsted acid catalysis is an important area of organocatalysis. We recently described an intramolecular iminium-ion cyclization reaction of 2-alkenylbenzaldimines catalyzed by a chiral Brønsted acid (a BINOL-derived N-triflylphosphoramide) for the synthesis of chiral 1-aminoindenes and tetracyclic 1-aminoindanes in good yields and high enantioselectivities. One of the resulting 1-aminoindenes is a useful intermediate for the synthesis of (S)-rasagiline, an effective drug for the symptomatic treatment of Parkinson’s disease. Moreover, some tetracyclic 1-aminoindanes are present in the skeletons of homoisoflavanoid natural products such as brazilin.

This Account covers the recent progress made on heterocyclic mechanophores in the field of polymer mechanochemistry. In particular, the types of such mechanophores as well as the mechanisms and applications of their force-induced structural transformations are discussed and related perspectives and future challenges proposed.1 Introduction2 Types of Mechanophores3 Methods to Incorporate Heterocycle Mechanophores into Polymer Systems4 Mechanochemical Reactions of Heterocyclic Mechanophores4.1 Three-Membered-Ring Mechanophores4.2 Four-Membered-Ring Mechanophores4.3 Six-Membered-Ring Mechanophores4.4 Bicyclic Mechanophores5 Applications5.1 Cross-Linking of Polymer5.2 Degradable Polymer5.3 Mechanochromic Polymer6 Concluding Remarks and Outlook

This Account covers the recent progress made on heterocyclic mechanophores in the field of polymer mechanochemistry. In particular, the types of such mechanophores as well as the mechanisms and applications of their force-induced structural transformations are discussed and related perspectives and future challenges proposed.1 Introduction2 Types of Mechanophores3 Methods to Incorporate Heterocycle Mechanophores into Polymer Systems4 Mechanochemical Reactions of Heterocyclic Mechanophores4.1 Three-Membered-Ring Mechanophores4.2 Four-Membered-Ring Mechanophores4.3 Six-Membered-Ring Mechanophores4.4 Bicyclic Mechanophores5 Applications5.1 Cross-Linking of Polymer5.2 Degradable Polymer5.3 Mechanochromic Polymer6 Concluding Remarks and Outlook

In this paper, ynolate-initiated cycloaddition (annulation) to form a range of carbocycles and heterocycles is described. Ynolates consist of a ketene anion equivalent, which contains both nucleophilic and electrophilic moieties, and a carbodianion equivalent that achieves double addition. Hence, in addition to the usual [n+2] cycloaddition, ynolates can perform formal [n+1]-type annulations. Their high-energy performance has been demonstrated by their triple addition to arynes to generate triptycenes, in which the C–C triple bond of ynolates is cleaved. The synthetic applications of these methods, including natural products synthesis, are also described.1 Introduction2 Preparation of Ynolates2.1 Double Lithiation2.2 Flow Synthesis2.3 Double Deprotonation3 [2+2] Cycloaddition to C=O Bond3.1 To Aldehydes and Ketones3.2 Sequential Cycloaddition4 [2+2] Cycloaddition to Imino Groups

In this paper, ynolate-initiated cycloaddition (annulation) to form a range of carbocycles and heterocycles is described. Ynolates consist of a ketene anion equivalent, which contains both nucleophilic and electrophilic moieties, and a carbodianion equivalent that achieves double addition. Hence, in addition to the usual [n+2] cycloaddition, ynolates can perform formal [n+1]-type annulations. Their high-energy performance has been demonstrated by their triple addition to arynes to generate triptycenes, in which the C–C triple bond of ynolates is cleaved. The synthetic applications of these methods, including natural products synthesis, are also described.1 Introduction2 Preparation of Ynolates2.1 Double Lithiation2.2 Flow Synthesis2.3 Double Deprotonation3 [2+2] Cycloaddition to C=O Bond3.1 To Aldehydes and Ketones3.2 Sequential Cycloaddition4 [2+2] Cycloaddition to Imino Groups

The Account describes recent advances, from the authors’ laboratories, in the synthesis of diverse libraries of small-molecule building blocks employing ionic liquids (ILs). The ability of ILs to act as catalysts/promoters/solvents for electrophilic and onium ion chemistry, as well as in metal-mediated cross-coupling reactions, and the potential to sequence/hyphenate these methods, have opened up new opportunities for facile assembly of functional small molecules with increased complexity from readily available precursors. While Brønsted acidic IL/IL solvent mixtures are suitable media for carbocation and onium ion chemistry, piperidine-appended IL/IL solvent mixtures can successfully catalyze a variety of base-catalyzed reactions. Several widely practiced transformations including ‘name reactions’ were adapted and performed efficiently in ILs.1 Introduction2 Aryldiazonium Salts and Aryltriazenes as Coupling Partners in Metal-Mediated C–C Cross-Coupling Reactions in ILs3 Expanding the Scope of Metal-Mediated Cross-Coupling Reactions in ILs4 Application of ILs in Synthesis and Functionalization of Hetero­cycles5 Expanding the Scope of Amide Synthesis in ILs6 Generation and Chemistry of ‘Tamed’ Propargylic Cations in ILs7 Newer Nitration Methods for Arenes and Heteroarenes in ILs8 Halofunctionalization in ILs9 ‘Name Reactions’and Other Widely Practiced Synthetic Transformations in ILs9.1 The Biginelli Reaction9.2 Nitrile Synthesis by the Schmidt Reaction9.3 Rupe Rearrangement9.4 Synthesis of 1,3-Dioxanes via Prins Reaction in [BMIM(SO3H)][OTf]9.5 Synthesis of Cyclopropanes and Oxiranes by the Corey–Chaykovsky (CC) Reaction10 Conclusions and Closing Remarks

The Account describes recent advances, from the authors’ laboratories, in the synthesis of diverse libraries of small-molecule building blocks employing ionic liquids (ILs). The ability of ILs to act as catalysts/promoters/solvents for electrophilic and onium ion chemistry, as well as in metal-mediated cross-coupling reactions, and the potential to sequence/hyphenate these methods, have opened up new opportunities for facile assembly of functional small molecules with increased complexity from readily available precursors. While Brønsted acidic IL/IL solvent mixtures are suitable media for carbocation and onium ion chemistry, piperidine-appended IL/IL solvent mixtures can successfully catalyze a variety of base-catalyzed reactions. Several widely practiced transformations including ‘name reactions’ were adapted and performed efficiently in ILs.1 Introduction2 Aryldiazonium Salts and Aryltriazenes as Coupling Partners in Metal-Mediated C–C Cross-Coupling Reactions in ILs3 Expanding the Scope of Metal-Mediated Cross-Coupling Reactions in ILs4 Application of ILs in Synthesis and Functionalization of Hetero­cycles5 Expanding the Scope of Amide Synthesis in ILs6 Generation and Chemistry of ‘Tamed’ Propargylic Cations in ILs7 Newer Nitration Methods for Arenes and Heteroarenes in ILs8 Halofunctionalization in ILs9 ‘Name Reactions’and Other Widely Practiced Synthetic Transformations in ILs9.1 The Biginelli Reaction9.2 Nitrile Synthesis by the Schmidt Reaction9.3 Rupe Rearrangement9.4 Synthesis of 1,3-Dioxanes via Prins Reaction in [BMIM(SO3H)][OTf]9.5 Synthesis of Cyclopropanes and Oxiranes by the Corey–Chaykovsky (CC) Reaction10 Conclusions and Closing Remarks