Darren Poole

O₂ will do: A dehydrogenative amination coupling of amines with phenols is described, which operates without halides or metal salts and utilizes O₂ as sole oxidant. The reaction is atom-economical and tolerates a range of functional groups.

[Communication]
Marie-Laure Louillat-Habermeyer, Rongwei Jin, Frederic W. Patureau
Angew. Chem. Int. Ed., February 5, 2015, DOI: 10.1002/anie.201500089. Read article.

Prof. Dr. Chun-Yu Ho, Chun-Wa Chan and Lisi He

Crossed: An asymmetric tail-to-tail cross-hydroalkenylation of vinylarenes with terminal olefins was catalyzed by NiH complexes with chiral N-heterocyclic carbenes (NHCs). Depending on steric and electronic effects of the substrates and NHC ligands, the reaction can provide branched gem-disubstituted olefins with high enantio- (up to 94 % ee) and chemoselectivity (cross/homo product ratio: up to 99:1).

Read more now

An operationally simple manganese-catalyzed C-H functionalization of ketimines provides access to β-amino acid esters. The mechanism of this transformation was studied, and its utility proven by further modifications of the synthetically useful β-amino acid esters into attractive compounds.

[Communication]
Weiping Liu, Daniel Zell, Michael John, Lutz Ackermann
Angew. Chem. Int. Ed., February 6, 2015, DOI: 10.1002/anie.201411808. Read article.

It all adds up: A novel pathway for oxa-Michael addition to challenging β-substituted unsaturated nitrile substrates is described based on a dearomatized ruthenium PNN pincer catalyst (see picture). Metal–ligand cooperative activation of the nitrile is key to the observed reactivity.

[Communication]
Sébastien Perdriau, Douwe S. Zijlstra, Hero J. Heeres, Johannes G. de Vries, Edwin Otten
Angew. Chem. Int. Ed., February 6, 2015, DOI: 10.1002/anie.201412110. Read article.

Flora W. Kimani and Dr. John C. Jewett

Just add water: Triazabutadienes readily release diazonium species in a pH-dependent manner in a series of buffer solutions with pH ranges similar to those found in living systems. These compounds offer one of the mildest ways of generating diazonium species in aqueous solutions.

Read more now

Two nucleophiles: The first cross-coupling reaction between aryl silanes and aryl boronic acids is one of the very few examples of coupling reactions between two nucleophilic organometallic reagents and provides access to biaryl compounds. With the commercially available ligand BINAP, the formation of the homocoupling products was suppressed, and the reaction yielded the cross-coupling products with high selectivity.

[Communication]
Jingxun Yu, Jun Liu, Guangfa Shi, Changdong Shao, Yanghui Zhang
Angew. Chem. Int. Ed., February 3, 2015, DOI: 10.1002/anie.201412288. Read article.

Aryl ester electrophiles are used in an enantioselective C-C bond formation through C-O bond cleavage. This reaction proceeds under nickel catalysis by means of an axially chiral bidentate ligand, allowing the formation of enantioenriched quaternary stereocenters. This protocol is characterized by its high asymmetric induction and remarkable wide scope.

[Communication]
Josep Cornella, Evan P. Jackson, Ruben Martin
Angew. Chem. Int. Ed., February 4, 2015, DOI: 10.1002/anie.201412051. Read article.

Alkyne plus alkyne: The hydroalkynylation of phenoxy alkynes was achieved with high regio-, chemo-, and stereoselectivities. A catalytic amount of [Pd(PPh₃)₂Cl₂] with 2.5 equiv. of NEt₃ could mediate the reaction without the need for a ligand, or a Cu catalyst for the activation of the terminal alkyne. The products with allylic hydroxy tether are convenient precursors for useful enynones. pTSA=p-toluenesulfonic acid.

[Communication]
Madala Hari Babu, Vikas Dwivedi, Ruchir Kant, Maddi Sridhar Reddy
Angew. Chem. Int. Ed., February 4, 2015, DOI: 10.1002/anie.201411261. Read article.

In a pinch: An NCP pincer/iridium catalyst is highly efficient for α-alkylation of unactivated esters using alcohol under mild reaction conditions. The reaction is simple, clean, and scalable (1–10 mmol), and the scope with respect to the ester is wide.

[Communication]
Le Guo, Xiaochen Ma, Huaquan Fang, Xiangqing Jia, Zheng Huang
Angew. Chem. Int. Ed., February 4, 2015, DOI: 10.1002/anie.201410293. Read article.

Metal-catalysed azidation of tertiary C–H bonds suitable for late-stage functionalization

Nature 517, 7536 (2015). doi:10.1038/nature14127

Authors: Ankit Sharma & John F. Hartwig

Many enzymes oxidize unactivated aliphatic C–H bonds selectively to form alcohols; however, biological systems do not possess enzymes that catalyse the analogous aminations of C–H bonds. The absence of such enzymes limits the discovery of potential medicinal candidates because nitrogen-containing groups are crucial to the biological activity of therapeutic agents and clinically useful natural products. In one prominent example illustrating the importance of incorporating nitrogen-based functionality, the conversion of the ketone of erythromycin to the –N(Me)CH2– group in azithromycin leads to a compound that can be dosed once daily with a shorter treatment time. For such reasons, synthetic chemists have sought catalysts that directly convert C–H bonds to C–N bonds. Most currently used catalysts for C–H bond amination are ill suited to the intermolecular functionalization of complex molecules because they require excess substrate or directing groups, harsh reaction conditions, weak or acidic C–H bonds, or reagents containing specialized groups on the nitrogen atom. Among C–H bond amination reactions, those forming a C–N bond at a tertiary alkyl group would be particularly valuable, because this linkage is difficult to form from ketones or alcohols that might be created in a biosynthetic pathway by oxidation. Here we report a mild, selective, iron-catalysed azidation of tertiary C–H bonds that occurs without excess of the valuable substrate. The reaction tolerates aqueous environments and is suitable for the functionalization of complex structures in the late stages of a multistep synthesis. Moreover, this azidation makes it possible to install a range of nitrogen-based functional groups, including those from Huisgen ‘click’ cycloadditions and the Staudinger ligation. We anticipate that these reactions will create opportunities to modify natural products, their precursors and their derivatives to produce analogues that contain different polarity and charge as a result of nitrogen-containing groups. It could also be used to help identify targets of biologically active molecules by creating a point of attachment—for example, to fluorescent tags or ‘handles’ for affinity chromatography—directly on complex molecular structures.