Electrochemical Ruthenium-Catalysed C–H Activation in Water Through Heterogenization of a Molecular Catalyst

Efficient catalytic oxidative C–H activation of organic substrates remains an important challenge in synthetic chemistry. Here, we show that the combination of a transition metal catalyst, surface immobilisation and an...

Correction: The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions

Correction for ‘The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions’ by Bee Ha Gan et al., Chem. Soc. Rev., 2021, 50, 7820–7880, DOI: 10.1039/D0CS00729C.

Continuous flow technology-A tool for safer oxidation chemistry

The oxidation reaction is one of the most important transformations in synthetic chemistry, allowing for the introduction and modification of various functional groups. Continuous flow chemistry involving the use of...

Facile Synthesis of the Dicyanophosphide Anion via Electrochemical Activation of White Phosphorus: An Avenue to Organophosphorus Compounds

Organophosphorus compounds (OPCs) have gained tremendous interest in the past decades due to their wide applications ranging from synthetic chemistry to materials and biological sciences. We describe herein a practical and versatile approach for the transformation of white phosphorus (P4) into useful OPCs with high P atom economy via a key bridging anion [P(CN)2]–. This anion can be prepared on a gram scale directly from P4 through an unprecedented electrochemical process. A variety of OPCs involving phosphinidenes, cyclophosphanes and phospholides have been made readily accessible from P4 in a two-step manner. Our approach has a significant impact on the future preparation of OPCs in laboratory and industrial settings.

A Personal Account on Industrial Collaborations in the Field of C–H Activation

In recent years, transition-metal-catalyzed C–H functionalization has emerged as a potentially greener alternative to classic cross-couplings and as a powerful tool to access complex functional molecules with improved step-economy. This short account relates our experience of industrial collaborations in C(sp3)–H bond activation, which were key to the development of this topic in our group. The synthesis of the antianginal drug Ivabradine led us to develop a general approach to benzocyclobutenes, which were further employed in peri cyclic reactions. A follow-up study led us to discover a new method to construct arylcyclopropanes via double C–H activation and the coupling of two alkyl groups. Finally, targeting the herbicide Indaziflam contributed to develop C(sp3)–H activation as a powerful tool to access a variety of relevant indane motifs. We hope that these successful stories will help to stimulate further fruitful Industry-Academia collaborations in the field of synthetic chemistry.

Copper-Catalyzed Synthesis of Coumarins. A Mini-Review

Coumarin (2H-chromen-2-one) derivatives have important uses in medicinal and synthetic chemistry, for example, as fluorescent probes. These properties have prompted chemists to develop efficient synthetic methods to synthesize the coumarin core and/or to functionalize it. In this context, many metal-catalyzed syntheses of coumarins have been introduced; among them, copper-catalyzed reactions appear to be very promising owing to the non-toxicity and cheapness of copper complexes. In this mini-review, the results in this field are summarized. We hope to stimulate other applications of these complexes in the preparation of coumarin derivatives.

Azulene-based Protecting Groups

<p>Protecting groups form an indispensable part of modern organic synthetic chemistry. Besides the benefits of selectively passivating certain reactive functionalities, they often provide handling benefits – such as a decrease in the polarity of the compound that facilitates purification, an increase in the structural order of a compound that allows for easier crystallisation, and chromophores that enable easy visualisation on fluorescent TLC plates under UV light. Coloured protecting groups offer additional advantages in synthetic chemistry. They expedite purification by allowing the material to be tracked visually. Phase separation and column chromatography are easier to perform, and reduce the need for the collection of large numbers of fractions, while small-scale loss of material (left behind on taps or in flasks during routine handling) and spillages are much more readily apparent. Despite these advantages, only a few coloured protecting groups have been reported in the literature. The azulenes are a class of compounds with several attractive qualities that can be exploited for use as protecting groups. They are coloured, but not overwhelmingly so. The colour is tunable through placement of electron-donating or electron-withdrawing groups at positions on the ring system, which further allows for protection/deprotection reactions to be designed that incorporate a colour change. Azulene itself is both non-polar and structurally compact, unlike many other organic chromophores such as triarylmethane dyes and carotenoids. Furthermore, azulene’s ability to stabilise both positive and negative charges through resonance with tropylium and cyclopentadienide motifs allows for unusual chemistry, and therefore potentially orthogonal modes of deprotection. Four protecting group candidates incorporating azulene were devised. The 1-azulenylmethylene amine 79 and the 1-azulenesulfonamide 82 protecting group candidates for amines had fatal flaws that were discovered early, such as a tendency to rapidly degrade in open air. The 1-azulenecarboxylate protecting group candidate 74 for alcohols showed some promise, with a high-yielding protection reaction, but none of the deprotection conditions that were developed were sufficiently mild to be usable in a late-stage deprotection strategy on a complex target molecule. The final protecting group candidate, 6-(2-[oxycarbonyl]ethyl)azulene 89, can be used for the protection of carboxylic acids, amines and alcohols as esters, carbamates and carbonates, respectively. The substitution at the 6-position of azulene allows for deprotection through an E1cB mechanism with mild base, involving a cyclopentadienide-stabilised carbanion intermediate, in a similar fashion to the FMOC protecting group. Mild conditions for the protection of all three were found: for carboxylic acids Steglich esterification is employed, and for alcohols and amines coupling with CDI is used. A selection of mild protocols for deprotection were developed, using bases such as DBU or TBAF, or involving two-step activation-deprotection procedures. Finally, the compatibility of the protecting group 89 (dubbed Azul) with common and representative procedures in synthetic chemistry was investigated, such as with bases and with reaction conditions such as oxidations, reductions, cross-couplings, etc. Orthogonality with other common protecting groups (such as TBS, MOM, FMOC) was also explored. Some incompatibilities were found with strongly acidic conditions, high-temperature Suzuki cross-coupling reactions and Swern oxidations, but otherwise the Azul protecting group shows promise as a protecting group that expedites total synthesis through its colourful properties.</p>

Azulene-based Protecting Groups

<p>Protecting groups form an indispensable part of modern organic synthetic chemistry. Besides the benefits of selectively passivating certain reactive functionalities, they often provide handling benefits – such as a decrease in the polarity of the compound that facilitates purification, an increase in the structural order of a compound that allows for easier crystallisation, and chromophores that enable easy visualisation on fluorescent TLC plates under UV light. Coloured protecting groups offer additional advantages in synthetic chemistry. They expedite purification by allowing the material to be tracked visually. Phase separation and column chromatography are easier to perform, and reduce the need for the collection of large numbers of fractions, while small-scale loss of material (left behind on taps or in flasks during routine handling) and spillages are much more readily apparent. Despite these advantages, only a few coloured protecting groups have been reported in the literature. The azulenes are a class of compounds with several attractive qualities that can be exploited for use as protecting groups. They are coloured, but not overwhelmingly so. The colour is tunable through placement of electron-donating or electron-withdrawing groups at positions on the ring system, which further allows for protection/deprotection reactions to be designed that incorporate a colour change. Azulene itself is both non-polar and structurally compact, unlike many other organic chromophores such as triarylmethane dyes and carotenoids. Furthermore, azulene’s ability to stabilise both positive and negative charges through resonance with tropylium and cyclopentadienide motifs allows for unusual chemistry, and therefore potentially orthogonal modes of deprotection. Four protecting group candidates incorporating azulene were devised. The 1-azulenylmethylene amine 79 and the 1-azulenesulfonamide 82 protecting group candidates for amines had fatal flaws that were discovered early, such as a tendency to rapidly degrade in open air. The 1-azulenecarboxylate protecting group candidate 74 for alcohols showed some promise, with a high-yielding protection reaction, but none of the deprotection conditions that were developed were sufficiently mild to be usable in a late-stage deprotection strategy on a complex target molecule. The final protecting group candidate, 6-(2-[oxycarbonyl]ethyl)azulene 89, can be used for the protection of carboxylic acids, amines and alcohols as esters, carbamates and carbonates, respectively. The substitution at the 6-position of azulene allows for deprotection through an E1cB mechanism with mild base, involving a cyclopentadienide-stabilised carbanion intermediate, in a similar fashion to the FMOC protecting group. Mild conditions for the protection of all three were found: for carboxylic acids Steglich esterification is employed, and for alcohols and amines coupling with CDI is used. A selection of mild protocols for deprotection were developed, using bases such as DBU or TBAF, or involving two-step activation-deprotection procedures. Finally, the compatibility of the protecting group 89 (dubbed Azul) with common and representative procedures in synthetic chemistry was investigated, such as with bases and with reaction conditions such as oxidations, reductions, cross-couplings, etc. Orthogonality with other common protecting groups (such as TBS, MOM, FMOC) was also explored. Some incompatibilities were found with strongly acidic conditions, high-temperature Suzuki cross-coupling reactions and Swern oxidations, but otherwise the Azul protecting group shows promise as a protecting group that expedites total synthesis through its colourful properties.</p>