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“Iron-Catalyzed C-H Borylation of Arenes” Dombray, T.; Werncke, C. G.; Jiang, S.; Grellier, M.; Vendier, L.; Bontemps, S.; Sortais, J-B.; Sabo-Etienne, S.; Darcel, C. J. Am. Chem. Soc. 2015, ASAP. DOI: 10.1021/jacs.5b00895
C-H borylation, itself a green reaction for generating useful borylated compounds, is traditionally catalyzed by Ir and Rh. Much of the work has been conducted by John Hartwig’s group at Berkeley and Mitch Smith’s group at Michigan St. French scientists have now reported an iron-catalyzed version, which complements recent reports with Co complexes and dinuclear transition metal complexes. I especially like that the reported reaction is free of H2 acceptors and utilizes light to activate the catalyst.
“Selective Metal-Catalyzed Transfer of H2 and CO from Polyols to Alkenes” Verendel, J. J.; Nordlund, M.; Andersson, P. G. ChemSusChem, 2013, 6, 426-429. DOI: 10.1002/cssc.201200843
In a recent post I commented on the byproducts of dehydrogenative decarbonylation, namely H2 and CO.
I wondered whether this gas mixture, syngas, could be used in a subsequent reaction. This would improve the atom efficiency of the reaction and potentially also improve the safety (of both the syngas-producing and syngas-using reactions). Both are goals of green chemistry and I especially appreciate avoiding rolling cylinders of toxic and/or flammable gases around the lab.
“Acceptorless Photocatalytic Dehydrogenation for Alcohol Decarbonylation and Imine Synthesis.” Ho, H-A.; Manna, K.; Sadow, A. D. Angew. Chem. Int. Ed. 2012, 51, 8607-8610. DOI: 10.1002/anie.201203556
The use of biorenewables as feedstock chemicals for commodity chemicals as well as fuels requires mild, selective removal of oxygen-containing functional groups. This is in direct contrast to the production of these chemicals from petroleum products, which, at least for highly functionalized target molecules, necessarily involves oxygenation of hydrocarbons.
There are a large amount of methods development currently underway and I highlight the recent report from the Sadow group on the decarbonylation of alcohols under Rh catalysis. I think the described reaction is a good example of green chemistry, as the reaction is high-yielding, selective, and performed at room temperature under photocatalytic conditions. One serious drawback is the use of benzene as the solvent, although toluene works as a solvent in at least some cases.
Reasoning that photolysis would prevent catalyst inhibition by CO binding, the researchers first screened Rh(I) catalysts under photocatalytic conditions with the test substrate cyclohexanemethanol. Unfortunately, no cyclohexane was observed under these reaction conditions. The group then tested Rh and Ir compounds known for C-H activation, such as Cp*Ir(CO)2 and Tp*Rh(CO)2, and did observe cyclohexane for one of the tested catalysts, albeit in low yield (36 % NMR yield with Tp*Rh(CO)2). CO and H2 were also observed, consistent with the targeted alcohol decarbonylation reaction. Interestingly, using their previously reported rhodium tris(oxazolinyl)borate complex ToMRh(CO)2 (1) improved the yield to > 95%. Furthermore, the related dihydride, ToMRh(H)2CO (2) was roughly three times slower and the Ir complex ToMIr(CO)2 was inactive for this reaction.
“Stereocontrolled organocatalytic synthesis of prostaglandin PGF2α in seven steps” Coulthard, G.; Erb, W.; Aggarwal, V. K. Nature 2012, online view. DOI: 10.1038/nature11411
In my very un-scientific survey of the green chemistry-branded journals, I see way more new methodologies than I see total syntheses. I hope to single-handedly change this, and show how green a total synthesis can be by writing about the awesome recent synthesis of prostaglandin PGF2α by Aggarwal and coworkers. First, a few words on the target molecule. Being hormones, prostaglandins such as PGF2α are involved in tons of biological processes. Interestingly, instead of being synthesized by some important gland and acting in far-off regions of the body as are endocrine hormones, they are autocrine or paracrine hormones and are synthesized “on-site.” The first structural characterizations of prostaglandins came in the 1960s, some 30 years after their initial discovery. Soon after, they became the subject of numerous syntheses, the first of which was achieved by E. J. Corey in 1969. A series of syntheses followed, but even 40 years later, the structurally-related glaucoma drug latanoprost is synthesized in 20 steps using Corey’s 1969 prostaglandin strategy.
That’s right, the prostglandin structural motif is medicinally relevant. So, not only would an improved synthesis be cool from a fundamental science perspective, it might actually be moved into industrial production and have an immediate impact! (more…)
“TPGS-750-M: A Second-Generation Amphiphile for Metal-Catalyzed Cross-Couplings in Water at Room Temperature” Lipshutz, B. H.; Ghorai, S.; Abela, A. R.; Moser, R.; Nishikata, T.; Duplais, C.; Krasovskiy, A.; Gaston, R. D.; Gadwood, R. J. Org. Chem. 2011, 76, 4379-4391. DOI: 10.1021/jo101974u
I occasionally run reactions in water, and it is awesome. I LOVE not worrying as much about cancer. Unfortunately many interesting chemicals are simply too hydrophobic to allow reactions to be run in aqueous solution. As anyone who has ever scrubbed a greasy pan will know, one way to get around the solubility problem is with soap. Also called emulsifiers, surfactants, amphiphiles, a soap by any name is pretty much the same thing in my mind (though others will disagree I’m sure). Molecules with hydrophilic and hydrophobic ends can form micelles in water, creating variously-shaped and sized particles with hydrophobic cores. Using those hydrophobic cores as reaction media is a concept known as micellar catalysis. The Lipshutz group was not the first player in this arena, but they have been at it for some time. They recently teamed up with the medicinal chemistry company Kalexsyn and came out with a new amphiphile that caught my eye, dubbed TPGS-750-M.
“Development of a Continuous Flow Scale-Up Approach of Reflux Inhibitor AZD6906” Gustafsson, T.; Sörensen, H.; Pontén, F. Org. Proc. Res. Dev. 2012, ASAP. DOI: 10.1021/op200340c
“Continuous-Flow Synthesis of the Anti-Malaria Drug Artemisinin.” Lévesque, F.; Seeberger, P. H. Angew. Chem. Int. Ed.. 2012, 51, 1706-1709. DOI: 10.1002/anie.201107446
“Monitoring and Control of a Continuous Grignard Reaction for the Synthesis of an Active Pharmaceutical Ingredient Intermediate Using Inline NIR spectroscopy” Cervera-Padrell, A. E.; Nielsen, J. P.; Pedersen, M. J.; Christensen, K. M.; Mortensen, A. R.; Skovby, Dam-Johansen, T. K.; Kiil, S.; Gernaey, K. V. Org. Proc. Res. Dev. 2012, ASAP. DOI: 10.1021/op2002563
A little while back I wrote about an aerobic oxidation which was greatly improved by switching from a traditional round bottom flask setup to a continuous flow reactor – basically, continuous flow reactors are much better at handling oxygen, especially on scale. But most of the advantages of the flow reactor were specific to that reaction, and it wasn’t clear to me how a flow process would improve a reaction that doesn’t use oxygen, or some other gas. Fortunately, a lot has been published since then to help me get a handle on how continuous flow reactions can contribute towards greener processes. In particular, this review covers continuous processing within a green chemistry context, and Organic Process Research and Developement has a continuous flow themed issue in their ASAP section, including this process-oriented review (speaking of OPRD, check out this recent editorial concerning solvent selection and green chemistry). It turns out that flow chemistry can improve processes in a bunch of different ways, and it’s hard to get a sense for how this can work by just looking at one reaction. So I’ll cover a few different reactions that illustrate different green aspects of continuous flow reactors.
One benefit of flow reactors is improved control over reaction temperature, due to reduced reaction volume at a given time, higher surface area, and the movement of the reaction mixture. This is particularly helpful for very exothermic reactions, which often require cryogenic cooling to prevent runaway reactions – this type of cooling is very expensive and resource-intensive on a large scale. One such reaction is described in a recent paper from AstraZeneca, in which a phosphinate anion adds into a glycine derivative. The product of this reaction is an intermediate in the synthesis of a gastroesophageal reflux inhibitor drug candidate called AZD6906.
“Iron-Catalyzed Intramolecular Allylic C-H Amination” Paradine, S. M.; White, M. C. J. Am. Chem. Soc. 2012, 134, 2036-2039. DOI: 10.1021/ja211600g
In their recent communication, Christina White’s group at Illinois reports a new allylic C-H amination catalyzed by iron. This builds on previous work from their group in Pd sulfoxide catalyzed allylic amination and iron catalyzed C-H oxidation. In addition to showcasing an exciting reaction, this paper is a great contribution from a green chemistry perspective: they use a cheap, non-toxic metal catalyst to do a highly selective C-H oxidation reaction, one that streamlines the synthesis of C-N bonds directly from the (relatively) unreactive C-H bond. Interestingly, quantitative comparisons are made throughout the paper to the more commonly used Rh2(OAc)4 catalyst.
They start by screening Fe catalysts for intramolecular allylic amination reactivity of sulfamate substrates. Although the polypyridyl Fe complex they have used previously for hydroxylation and desaturation chemistry gave a low yield of product, the phthalocyanine Fe complex 1 gave a good yield (and better than a tetraphenylporphyrin iron complex) of allylic amination. Importantly, they obtained only trace quantities of the aziridination product, showing the high selectivity of the iron-catalyzed reaction (>20:1).
“Green Nanochemistry: Metal Oxide Nanoparticles and Porous Thin Films from Bare Metal Powders” Engelbert Redel, Srebri Petrov, Ömer Dag , Jonathon Moir, Chen Huai, Peter Mirtchev, and Geoffrey A. Ozin, Small, 2011, DOI: 10.1002/smll.201101596
Advocates for green chemistry and nanotechnology have both promised technological solutions to society’s great challenges. Some of the barriers to widespread adoption of nanotechnology have been outlined by Jim Hutchison, and many of these barriers can be addressed by green chemistry. In particular the two issues that the current paper addresses are the excessive waste and the potential hazards associated with the metal precursors.