Scalable total synthesis and comprehensive structure-activity relationship studies of the phytotoxin coronatine.

Natural phytotoxins are valuable starting points for agrochemical design. Acting as a jasmonate agonist, coronatine represents an attractive herbicidal lead with novel mode of action, and has been an important synthetic target for agrochemical development. However, both restricted access to quantities of coronatine and a lack of a suitably scalable and flexible synthetic approach to its constituent natural product components, coronafacic and coronamic acids, has frustrated development of this target.

Bioinspired Total Synthesis of Bussealin E.

The first total synthesis of bussealin E, a natural product with a unique cycloheptadibenzofuran scaffold, is reported. A strategy inspired by a proposed biosynthesis was employed whereby a diphenylpropane derivative underwent an oxidative phenolic coupling to forge the tetracyclic ring system. The synthesis of the diphenylpropane featured a key sp-sp Hiyama coupling between a vinyldisiloxane and a benzylic bromide.

Protein modification alkyne hydrosilylation using a substoichiometric amount of ruthenium(ii) catalyst.

Transition metal catalysis has emerged as a powerful strategy to expand synthetic flexibility of protein modification. Herein, we report a cationic Ru(ii) system that enables the first example of alkyne hydrosilylation between dimethylarylsilanes and -propargyl-functionalized proteins using a substoichiometric amount or low-loading of Ru(ii) catalyst to achieve the first C-Si bond formation on full-length substrates. The reaction proceeds under physiological conditions at a rate comparable to other widely used bioorthogonal reactions.

Palladium-catalysed cross-coupling of vinyldisiloxanes with benzylic and allylic halides and sulfonates.

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.

Aryl-aryl bond formation by the fluoride-free cross-coupling of aryldisiloxanes with aryl bromides.

The prevalence of the biaryl structural motif in biologically interesting and synthetically important molecules has inspired considerable interest in the development of methods for aryl-aryl bond formation. Herein we describe a novel strategy for this process involving the fluoride-free, palladium-catalysed cross-coupling of readily accessible aryldisiloxanes and aryl bromides. Using a statistical-based optimisation process, preparatively useful reaction conditions were formulated to allow the cross-coupling of a wide range of different substrates.