Cyclophanes are a venerable class of macrocyclic and cage compounds that often contain unusual conformations, high strain, and unusual properties. However, synthesis of complex, functional derivatives remains difficult due to low functional group tolerance, high dilution, extreme reaction conditions, and sometimes low yields using traditional stepwise synthetic methods. “Design of experiments” (DOE) is a method employed for the optimization of reaction conditions, and we showcase this approach to generate a dramatic increase in the yield of specific targets from two different self‐assembling systems. These examples demonstrate that DOE provides an additional tool in tuning self‐assembling, dynamic covalent systems.
Main Group Supramolecular Chemistry Led to Surprising New Directions in the Self-Assembly of Organic Macrocycles, Cages, and Cyclophanes
Abstract Cyclophanes are an admirable class of macrocyclic and cage compounds that often display unusual properties due to their high strain and unusual conformations. However, the exploration of new, complex cyclophanes has been encumbered by syntheses that can be low yielding, require harsh reaction conditions, and arduous purification steps. Herein, we discuss our work using metalloid-directed self-assembly and dynamic covalent chemistry to form cryptands. These were then subjected to mild conditions to produce discrete disulfide, thioether and hydrocarbon macrocycles in high yields. ‘Design of Experiments’ was then used to selectively synthesize targeted macrocycles from complex mixtures. 1 Introduction 2 Cryptands to Cyclophanes 3 Functionalizable Macrocycles 4 ‘Design of Experiments’ Targeted Synthesis 5 Conclusions and Outlook
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- NSF-PAR ID:
- 10309024
- Date Published:
- Journal Name:
- Synlett
- Volume:
- 32
- Issue:
- 17
- ISSN:
- 0936-5214
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Cyclophanes are a venerable class of macrocyclic and cage compounds that often contain unusual conformations, high strain, and unusual properties. However, synthesis of complex, functional derivatives remains difficult due to low functional group tolerance, high dilution, extreme reaction conditions, and sometimes low yields using traditional stepwise synthetic methods. “Design of experiments” (DOE) is a method employed for the optimization of reaction conditions, and we showcase this approach to generate a dramatic increase in the yield of specific targets from two different self‐assembling systems. These examples demonstrate that DOE provides an additional tool in tuning self‐assembling, dynamic covalent systems.
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Abstract Cyclophanes are a fundamentally interesting class of compounds that host a wide range of unique and emergent properties. However, synthesis of complex and/or functionalized cyclophanes can often suffer from harsh reaction conditions, long reaction times, and sometimes low yields using stepwise methods. We have previously reported an efficient, high‐yielding, metalloid‐directed self‐assembly method to prepare disulfide, thioether, and hydrocarbon cyclophanes and cages that feature mercaptomethyl‐arenes as starting materials. Herein, we report the synthesis of 21 new disulfide and thioether assemblies that expand this high yielding self‐assembly method to a wide breadth of macrocycles and cages with diverse structures. Remarkably, the high‐yielding, efficient syntheses still proceed under dynamic covalent control using electron‐deficient, heteroaryl, cycloalkyl, spiro, and even short alkenyl/alkynyl substrates.
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Abstract Here, we report an approach to the synthesis of highly charged enantiopure cyclophanes by the insertion of axially chiral enantiomeric binaphthyl fluorophores into the constitutions of pyridinium‐based macrocycles. Remarkably, these fluorescent tetracationic cyclophanes exhibit a significant AIE compared to their neutral optically active binaphthyl precursors. A combination of theoretical calculations and time‐resolved spectroscopy reveal that the AIE originates from limited torsional vibrations associated with the axes of chirality present in the chiral enantiomeric binaphthyl units and the fine‐tuning of their electronic landscape when incorporated within the cyclophane structure. Furthermore, these highly charged enantiopure cyclophanes display CPL responses both in solution and in the aggregated state. This unique duality of AIE and CPL in these tetracationic cyclophanes is destined to be of major importance in future development of photonic devices and bio‐applications.
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Abstract Here, we report an approach to the synthesis of highly charged enantiopure cyclophanes by the insertion of axially chiral enantiomeric binaphthyl fluorophores into the constitutions of pyridinium‐based macrocycles. Remarkably, these fluorescent tetracationic cyclophanes exhibit a significant AIE compared to their neutral optically active binaphthyl precursors. A combination of theoretical calculations and time‐resolved spectroscopy reveal that the AIE originates from limited torsional vibrations associated with the axes of chirality present in the chiral enantiomeric binaphthyl units and the fine‐tuning of their electronic landscape when incorporated within the cyclophane structure. Furthermore, these highly charged enantiopure cyclophanes display CPL responses both in solution and in the aggregated state. This unique duality of AIE and CPL in these tetracationic cyclophanes is destined to be of major importance in future development of photonic devices and bio‐applications.
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1055/a-1389-9498
