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Olefin hydroamination latest

22 May 2015 - Organic chemicstry

Latest from the Baran laboratory: Olefin hydroamination. (Gui et al. DOI) Key ingredients: an alkene and a nitro arene together with triphenylsilane (2 eq.), ferric acetylacetonate (30 mole%), zinc, HCl and ethanol. The product: the alkylated amine. Product optimisation and substrate scope are all accounted for but where is the reaction mechanism? Relax, it is hidden in the supplementary info (350 pages!).

Any mechanism involving iron is insanely complex but here is this blog's attempt at some understanding. Phenyl silane transfers a proton to ferric acetylacetonate to form a ferric hydride species Fe-H. This species reduces the nitro arene to the Ar-NO nitroso compound and at the same time it reacts with the alkene to the alkyl radical. Both intermediates then react to form the hydroxylamine Ar-N(OH)-R or the N,O adduct Ar-N(R)-OR. The hydroxylamine is then converted to the amine by a another iron species and the N,O adduct is reduced by zinc. Replacing iron by cobalt or manganese killed the reaction by the way so iron is really key.

Drawbacks: the alkene is added in large excess. Side-products are the amine as direct reduction product and the N,O adduct. Typical yields are in the range of 50-60% which sounds like not a lot but the article notes that isolating amines from a reaction product in general is a challenge. Nitroalkanes perform badly. Ketone, alcohol, boronic acid and amine functional groups are tolerated.

And how about that 350 page supplimentary information? It also includes a photographic guide with lots of experimental-setup close-ups. Those Baran people really dislike keeping the lab tidy!. Also included is a handy Q&A: how exactly do you monitor a reaction?

new CRD entry:
Gui et al 2015.PNG

Walk like an inchworm

16 May 2015 - Making It Move XV

molecular walkers haq 2015.PNGIn a new episode of Making-It-Move (previous one here) molecular walkers take the stage as reported by Haq et al. (DOI) . Walking or self-driving molecules have been around for some time. Unidirectional motion has not yet been achieved (the molecules stagger back and forth) and the new walker is not going to change that. New in the arena are especially designed fences for the walker to bounce back at.

Here are the details. The surface is copper. The walking event takes place at room-temperature. One type of porphyrin (Cobalt diphenylporphyrin) self-assembles into a fence measuring tens of nanometers thanks to interlinking copper atoms. The walker is 1,3-bis(imidazol-1-ylmethyl)benzene which when deposited on the copper surface adopts a horseshoe conformation. The imidazole feet can attach and detach from the surface because the N-Cu interaction is reversible. The spacer section allows the walker to take a leap when it detaches a foot. The walkers move perpendicular to the fences on copper tracks. Sure enough the Haq article has walkers moving between the fences in detailed STM images. With the fences really a short distance away the walkers are confined and can be accurately captured. With a larger distance between the fences the walkers can only be seen as a blur.

Get more out star anise

13 May 2015 - Expresso technology

The compound shikimic acid is a natural precursor in the production of the synthetic (and supposedly) anti-influenza drug oseltamivir (Tamiflu). See Oseltamivir total synthesis and previous blog episodes here, here, here, here and here. Nice to know that researchers from the School of Physical Sciences in Australia report on an improved method to isolate the acid from star anise here.

Current commercial isolation of shikimic acid is based on soxhlet extraction with a publicised yield of between 2.4 and 7%. The Australian researchers opted for pressurized hot water extraction (PHWE) using a regular espresso machine (this one). Here are the details: operation pressure: 9 bar, solvent: a 30% ethanol/water solution, rate: 2 minutes per 20 gram sample of star anise, workup: silica gel added and mixture dried, then product extracted with acetic acid/ethyl acetate solution. Yield: 5.5% and no chromatography!.

Safe acetylene source

09 May 2015 - Bench work

Matake, Niwa, and Matsubara report a new way to generate acetylene for research laboratory use. (DOI) The method is based on a phase-vanishing reaction (PV method): in a test tube a layer of fluorous solvent separates two reactive media that exchange reactants by slow diffusion, the reaction product then migrates to the top fourth reaction layer.

In the latest incarnation a PV method was deployed to generate acetylene in-situ in a Sonogashira coupling. A test tube was first filled with some calcium carbide, then a perfluoropolyether layer was added, then (carefully!) a layer of water and then on top a layer of tetrahydrofuran. This reaction layer contained all the ingredients for the coupling to take place: iodobenzene, tetrakis(triphenylphosphine)palladium(0), copper iodide and triethylamine. Heating to 55 °C was required in order to get the carbide react with water but then conversion reached 94% after 20 hours of stirring with complete disappearance of the calcium carbide.

Safe to use? Handling acetylene cylinders potentially pose bigger risks but the experimental setup still looks a bit adventurous: you still require to stir a heated test tube and then hope the carbide ball stays well away from the water.