B.R.S.M. The road to Tet. Lett. Is paved with good intentions


Superlatives 1: The Heaviest Catalyst Ever?

While browsing through the Advanced Synthesis and Catalysis Early View today, I noticed this paper on a new Rhodium catalyst for the asymmetric conjugate addition of boronic acids to enones in water. Pretty standard stuff... until you look at the catalyst structure. Now, I'm not particularly up on phosphine ligand design but I don't think that PEG and geranyl geranyl geranyl geranyl geranyl chains are a common thing to include. I mean, I've seen BINAP derivatives with some pretty big polyaromatic hydocarbon groups bolted on (e.g. anthracene and pyrene), but this is in a class of its own. In fact, I think that I can safely say that this is the largest catalyst for anything that I've ever seen. I guess the logic is that if you can't have the organic solvent in the flask you can just include it in the catalyst itself by larding it with hydrocarbon and polyether chains, and it does actually seem to work. A possible drawback of this approach is that the darn thing weighs more than maitotoxin and takes a total of twelve steps to make; all that just so we can have another way to add phenylboronic acid to cyclohexenone. I'm making a note of this for the next time someone calls my total synthesis project useless. Or am I being too harsh?

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  1. This reminds me of a story. My old research group does literature surveys once a month—group gets divided up to cover different journals, everyone picks their favorite articles from the past month, etc. It was an unspoken but important rule that the papers one picked should be “ground breaking,” and if they weren’t, an ass-reaming from the boss was to be expected. Perhaps the boss’s #1 pet peeve was conjugate addition catalysts…I remember, as a lowly first year (like I knew WTF a ground-breaking paper was back then), watching a visiting scientist get her ass handed to her after presenting a paper on a catalytic Michael reaction. Bet the old boss had a coronary when he saw this paper!

  2. That NMR data in full:

    1H NMR (400 MHz, CDCl3): δ 7.89 (d, J = 8.8 Hz, 1H), 7.85-7.82 (m, 2H), 7.64 (s, 1H), 7.43 (d, J = 8.4 Hz, 2H), 7.35 (t, J = 8.0 Hz, 1H), 7.21-7.05 (m, 20H), 6.93 (t, J = 8.0 Hz, 1H), 6.86 (d, J = 8.4 Hz, 1H), 6.73 (s, 2H), 5.13-4.97 (m, 10H), 4.29-4.26 (m, 2H), 3.81-3.80 (m, 6H), 3.72-3.46 (m, PEG), 3.39 (s, 3H), 3.21-3.19 (m, 2H), 2.97-2.92 (m, 2H), 2.84-2.77 (m, 4H), 2.63-2.56 (m, 2H), 2.10-1.92 (m, 41H), 1.73-1.55 (m, 33H);

    13C NMR (100 MHz, CDCl3): δ 171.9, 171.8, 171.3, 171.2, 170.3, 170.2, 145.1, 144.8, 143.3, 143.1, 140.6, 140.5, 140.3, 140.2, 139.3, 137.9, 137.8, 137.7, 137.5, 137.4, 137.1, 137.0, 135.7, 135.5, 135.4, 134.9, 134.7, 134.5, 134.3, 134.1, 133.9, 133.3, 133.1, 132.8, 132.7, 132.6, 131.9, 131.0, 130.6, 130.3, 128.3, 128.0, 127.9, 127.6, 127.5, 127.3, 126.9, 126.4, 125.7, 124.9, 124.7, 124.3, 124.1, 123.8, 121.1, 71.8-68.9 (PEG), 63.8, 60.6, 60.5, 58.9, 39.6, 34.8, 33.0, 28.9, 28.6, 26.6, 26.5, 26.3, 26.1, 25.6, 17.6, 16.2, 15.9, 12.1, 12.0;

  3. About the largest catalyst, you shouldn’t forget the Feringa DNA-based system:
    Angew. Chem. Int. Ed. 2005, 44, 3230–3232
    with a MW of 8000 g/mol more or less.

  4. the logic follows from previous work of Krasovsky who convinced Lipshutz to let him try palladium-catalyzed Negishi couplings with aryl zinc generated in situ in water (!) and it worked if you had greasy substrates and used a crapload of non-ionogenic detergent. So as to have a reasonably practical method (selling point of water-based chemistry) and be able to isolate anything from the whopping excess of detegent-water micellar soap, they made that detergent degradable, by having a succinyl-tocopherol (cheap, commercial) as the greasy part ester linked to PEG, so at the end they could hydrolyze the detergent apart. Having to work with Rh-phosphine ligands and form them in situ, having such catalyst covalently bound to the tocopherol is a step in very wrong direction, from practical point of view

    • I am in awe of your knowledge of chemistry!

      • its just coincidence – I am on friendly terms with Krasovsky so I got a scoop from him (after i teased him about organozincs run in water). Besides, a modification of PEG they used to make their cleavable detergent became useful to a subproject we worked at a company about a year ago…

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