Visible light photocatalysis allows the introduction of the sulfone functional group to anilines under mild reaction conditions, without the need for pre-functionalization.

The Hiyama cross-coupling reaction is a powerful method for carbon-carbon bond formation. To date, the substrate scope of this reaction has predominantly been limited to sp(2)-sp(2) coupling reactions. Herein, the palladium-catalysed Hiyama type cross-coupling of vinyldisiloxanes with benzylic and allylic bromides, chlorides, tosylates and mesylates is reported. A wide variety of functional groups were tolerated, and the synthetic utility of the methodology was exemplified through the efficient total synthesis of the cytotoxic natural product bussealin A. In addition, the antiproliferative ability of bussealin A was evaluated in two cancer-cell lines.

Heteroaromatic nitriles are important compounds in drug discovery, both for their prevalence in the clinic and due to the diverse range of transformations they can undergo. As such, efficient and reliable methods to access them have the potential for far‐reaching impact across synthetic chemistry and the biomedical sciences. Herein, we report an approach to heteroaromatic C−H cyanation through triflic anhydride activation, nucleophilic addition of cyanide, followed by elimination of trifluoromethanesulfinate to regenerate the cyanated heteroaromatic ring. This one‐pot protocol is simple to perform, is applicable to a broad range of decorated 6‐ring N‐containing heterocycles, and has been shown to be suitable for late‐stage functionalization of complex drug‐like architectures.

Resolvins D3 and E1 are important signaling molecules in the resolution of inflammation. Here, we report a convergent and flexible strategy to prepare these natural products using Hiyama–Denmark coupling of five- and six-membered cyclic alkenylsiloxanes to connect three resolvin fragments, and control the stereochemistry of the natural product (Z)-alkenes. The modular nature of this approach enables the synthesis of novel resolvin hybrids, opening up opportunities for more-extensive investigations of resolvin biology.

Cyclic dimethylalkenylsiloxanes, useful motifs for (Z)-selective Hiyama cross-coupling, are accessed from alkynyl benzyldimethylsilanes featuring adjacent allylic or homoallylic oxygen substituents by semihydrogenation/ debenzylation/cyclization. While formation of 5-and 6membered rings can be achieved from the free alcohols using fluoride or silanolate, allylic acetate precursors to 5-membered rings display distinct modes of activation. The utility of these compounds is demonstrated through the preparation of a variety of (Z)-alkene-containing polyenes and application to a concise total synthesis of leukotriene B 3 .

Cyclic alkenylsiloxanes were synthesized by semihydrogenation of alkynylsilanes—a reaction previously plagued by poor stereoselectivity. The silanes, which can be synthesized on multigram scale, undergo Hiyama–Denmark coupling to give (Z)-alkenyl polyene motifs found in bioactive natural products. The ring size of the silane is crucial: five-membered cyclic siloxanes also couple under fluoride-free conditions, whilst their six-membered homologues do not, enabling orthogonality within this structural motif.

The title Hiyama reaction is performed with allylic chlorides and bromides, and benzylic chlorides, bromides, tosylates and mesylates.

Synthesis of Cyclic Alkenylsiloxanes by Semihydrogenation: A StereospecificRoute to (Z)-Alkenyl Polyenes. -The general route to cyclic alkenylsiloxanes, based on the Lindlar hydrogenation of alkynylsilanes, solves a long-standing selectivity issue in alkynylsilane reduction chemistry. Although both five-and six-membered cyclic siloxanes undergo Hiyama-Denmark coupling to provide access to (Z)-alkenyl polyene motifs, only five-membered cyclic siloxanes are also able to couple under fluoride-free conditions, enabling orthogonality within this structural motif. Preparation of diene/triene segments of representative anticancer polyketide natural products, e.g. triene (XI), a fragment of fostriecin, underline the value and applicability of this methodology. -(ELBERT, B. L.; LIM, D. S. W.; GUDMUNDSSON, H. G.; O'HANLON, J. A.; ANDERSON*, E. A.; Chem. -Eur. J. 20 (2014) 28, 8594-8598, http://dx.doi.org/10.1002/chem.201403255 ; Chem. Res. Lab., Univ. Oxford, Oxford OX1 3TA, UK; Eng.) -H. Hoennerscheid 04-053