Organic & Biomolecular Chemistry Blog

This HOT Communication from Huaqiang Zeng and co-workers describes a 1D helical channel, composed of short foldamers with sticky ends that self-assemble in the solid state, that acts as a CH₂Cl₂ channel. What is interesting is that the Cl⋯Cl intermolecular distances within the channel are extraordinarily short. Zeng et al. perform computational modelling and calculate that this unusually short distance destabilises the host–guest complex by 14.94 kcal mol^-1.

This will be free to access for the next 4 weeks so why not have a look at modelling details.

Locking high energy 1D chain of dichloromethane molecules containing abnormally short Cl⋯Cl contacts of 2.524 Å inside organic crystals
Feng Zhou, Haoliang Fu, Wei Qiang Ong, Ruijuan Ye, Weixing Yuan, Yu-Jing Lu, Yan-Ping Huo, Kun Zhang, Haibin Su and Huaqiang Zeng
DOI: 10.1039/C2OB25888A

Biscarbazoles are a class of carbazole alkaloids in which two carbazole moieties are connected by different linkages. Oxydimurrayafoline is a special biscarbazole connecting two carbazole units via a benzylic ether linkage at the 3-position.

In this HOT Communication, Hans-Joachim Knölker and co-workers from Technische Universität Dresden, report the first total synthesis of oxydimurrayafoline via nucleophilic substitution at the benzylic position at the C-3 position of the carbazole framework.

Knölker et al. use a palladium catalysis approach to produce the key intermediate mukonine in 2 steps before going on to make oxydimurrayafoline in a total of 6 steps with an overall yield of 43%.

This Communication will be FREE to access for the next 4 weeks, so have a look at the details of the study today.

First total synthesis of the biscarbazole alkaloid oxydimurrayafoline
Carsten Börger, Micha P. Krahl, Margit Gruner, Olga Kataeva and Hans-Joachim Knölker
DOI: 10.1039/C2OB25842K

This Communication by Marco Bella et al. is a study of the historically famous Rabe amination, presenting preliminary results for a “modern” organocatalytic version of the reaction whereby direct functionalisation of ketones and aldehydes with N-chloro amines is achieved in mild conditions. Bella et al. also report that when aldehydes bearing a CH₂ moiety in the α-position are used, a novel rearrangement is observed leading to α-amino ketones.

Have a look at the Communication for more details on the experimental procedure and possible mechanistic explanation for this interesting reaction, it’s free to access for 4 weeks!

The Rabe amination after a century: direct addition of N-heterocycles to carbonyl compounds
Daniele M. Scarpino Schietroma, Mattia R. Monaco, Valerio Bucalossi, Philipp E. Walte, Patrizia Gentili and Marco Bella
DOI: 10.1039/C2OB25595B

Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) administered as a first-line treatment against HIV. Despite its efficacy, a major shortcoming is its association with toxic events. The reasons for the drug’s adverse effects are not currently clear, but in order to answer this question the availability of considerable amounts of enantiomerically pure EFV metabolites is essential, to allow in vitro and in vivo toxicological studies.

In this Hot paper Alexandra M. M. Antunes and co-workers report the development of a method for the direct aromatic hydroxylation of EFV, and other xenobiotics, using the easily accessible [Fe^II(bpmen)(OTf)₂]–H₂O₂ oxidant system in the presence of acetic acid. Antunes et al. say that “This cost-efficient one-pot strategy represents a considerable improvement when compared with the already available methods for the C8 hydroxylation of EFV, avoiding a laborious multi-step synthetic approach and the resolution of racemic mixtures.”

In addition to EFV, Antunes et al. successfully oxidise tamoxifen and equilin into their phenolic metabolites which demonstrates the general application of bio-inspired nonheme Fe-complexes for in vitro access to phenolic species typically formed via cytochrome P450 (CYP)-mediated hydroxylation of aromatic compounds. The possibility of applying an oxidation system mirroring the CYP metabolic pathways predicts the usefulness of the approach for molecular toxicology studies of a large variety of toxic aromatic xenobiotics.

This work represents a proof of concept regarding bio-inspired oxidation technologies and opens new opportunities for this chemistry. To find out more read the article in full here.

This paper will be free to access for the next 4 weeks.

Biomimetic oxidation of aromatic xenobiotics: synthesis of the phenolic metabolites from the anti-HIV drug efavirenz
Riccardo Wanke, David A. Novais, Shrika G. Harjivan, M. Matilde Marques and Alexandra M. M. Antunes
Org. Biomol. Chem., 2012,
DOI: 10.1039/C2OB25212K

In this HOT communication Corey R. J. Stephenson and colleagues at Boston University demonstrate the application of visible light-mediated photoredox catalysis for the synthesis of symmetric anhydrides. This new approach to anhydride formation proceeds via the activation of C–O bonds by the Vilsmeier–Haack reagent formed by Ru(bpy)₃Cl₂ and CBr₄ in DMF.

Stephenson et al. demonstrate the reaction with various aryl and alkyl carboxylic acids being converted to the corresponding anhydrides in excellent yields and they go on to show the efficacy of the method by performing scale-up reactions.

For the full reaction conditions have a look at this Communication today. As always, this HOT article will be free to access for the next 4 weeks!

Synthesis of symmetric anhydrides using visible light-mediated photoredox catalysis
Marlena D. Konieczynska ,  Chunhui Dai and Corey R. J. Stephenson
DOI: 10.1039/C2OB25463H