Bis(dirnethylphenylsi1yl)copper-lithium (1 ) reacts with hex-1 -yne, propyne, acetylene itself, phenylacetylene, and hex-3-yne to give the products of syn addition of the dimethylphenylsilyl group and the copper. The resultant vinylcopper reagents react with a variety of electrophiles, such as the prot.on, iodine, acyl and alkyl halides, enones, and epoxides, to give vinylsilanes. With the terminal alkynes, the silyl group becomes attached with a high level of regioselectivity to the terminal carbon atom, with the result that the final products are 2,2-disubstituted vinylsilanes. VINYLSILANES now occupy an established place inReaction OJ the Silylcuprate Reagent (1) with Acetylenes. organic synthesis, because they often react with electro--Dimethylphenylsilyl-lithium is easier to make than philes regio-and stereo-specifically,l and because their trimethylsilyl-lithium and we have used it throughout epoxides are masked aldehydes or ketones.2 However, in this work. We have no reason to expect the phenyl there are not many ways of preparing 2,e-disubstituted group to interfere seriously with the vinylsilane chemisvinylsilanes.3 In a preliminary comm~nication,~ we try which one might want to do subsequently. We find reported that our silylcuprate reagent (1) reacted with that the reagent ( l ) , prepared by mixing 2 mol equiv. of (Me, PhSi ),CuLi*LiCN / / \ \ terminal acetylenes, and the intermediate vinylcopper dimethylphenylsilyl-lithium with 1 mol equiv. of coppercompounds ( Z ) , (7), and (9) then reacted with the stan-(I) cyanide, reacts with hex-1-yne to give a vinylcopper dard electrophiles of organocopper chemistry to give species (2). When we quenched this intermediate with 2,2-disubstituted vinylsilanes (3), (8), and (10). We now water, we obtained only [>99% (by g.1.c. and lH n.m.r.)] report our work in full, and include further examples the vinylsilane (3a) in 94% yield based on the acetylene. establishing the scope of this easy vinylsilane synthesis. The silylcuprate reagent (1) had not removed the proton from the hexyne, as alkylcopper reagents do; this was t No reprints available.

The first five steps of the non-mevalonate pathway have been tested in high-throughput screening (HTS) campaigns, using enzymes of plant origin. Hit rates were in general relatively low, which could be attributed to the high polarity and charged nature of substrates and active sites of these enzymes. Still, for all the enzymes, apart from IspF (2-methylerythritol 2,4-cyclodiphosphate synthase), inhibitors could be identified with activities below 100 μM, and these were followed up to identify structure-activity relationships (SARs). For the enzyme IspD (2C-methyl-D-erythritol 4-phosphate cytidyltransferase), inhibitors with IC50 down to 35 nM were identified that also showed herbicidal activity.

The mixed silyl-cuprate reagent (6), made from 1 equiv. of methyl-lithium, 1 equiv. of phenyldimethylsilyl-lithium, and 1 equiv. of copper(t) cyanide, reacts with 3-methylcyclohexenone ( 7 ) , with methyl cinnamate (9), with 1 -vinylcyclohexyl acetate ( l l ) , and with hex-I -yne (13) to transfer, in each case, the silyl group, and to give the j3-silylcarbonyl compounds (8) and (1 0), the allylsilane (1 2), and the vinylsilane (1 4), without the concomitant formation of involatile silicon-containing byproducts. The silyl-cuprate reagent (1 5), prepared from trimethylsilyl-lithium and copper(!) cyanide, reacts with similar substrates, in the same way, even though hexamethylphosphoric triamide (HMPA) is present in the reaction medium.We have reported three types of reaction of the silyl-cuprate reagent (2). As shown in Scheme 1, these are (i) the conjugate

Trawling hundreds of antimalarials for herbicides, we develop a weighted scoring system for the phys-chem ‘rules’ of herbicide-likeness. Using this, we discover the antimalarial MMV1206386 is herbicidal via a novel mode of action.

We demonstrate that the antimalarial compound MMV007978 is also herbicidal and that exploiting lead compounds that are often understudied could lead to the identification of interesting herbicidal scaffolds. Further structural investigation of MMV007978 could provide improved herbicidal chemistries with a potential new mode of action. © 2018 Society of Chemical Industry.