Home » Still In The RBF

Rhazinocine   

19 March 2008 6,184 views 11 Comments

Gaunt , Beck and Hatley, ACIEE, 2008, EarlyView. DOI: 10.1002/anie.200705005. Article PDF Supporting Information Group Website ResearchBlogging.org

Another paper from Cambridge, this one from Matt Gaunt’s group. I’ve also seen development of the methodology behind this work progressing, and it’s nice to see it culminate in a smart and concise synthesis. Not much is mentioned about the natural product or it’s biological effects, other than “[it] mimic[s] the cellular effects of pacitaxel“, so are presumably also mitotic inhibitors. Retro time:

Perhaps the most obvious of disconnections is to cleave the amide bond in the medium ring, leaving two linked aromatic systems. The larger fragment would be assembled latterly, using the group’s regioselective oxidative PdII-cyclisation reaction, for which the SM is a more simple amide. Disconnection of the amide leaves a biaryl system which was constructed via a Suzuki coupling. And what a nice example of a Suzuki it is too…

In situ borylation with a bit of meteorite-catalyst selectively forms the boronic ester on the C-3 position of the pyrrole, on the less-substituted side. Changing to a less exotic catalyst system and adding the aryl iodide resulted in a high-yielding one-pot synthesis of the desired biaryl unit. Nice!

The synthesis of the acidic partner for the amide SM below is through a rather smart sequence of reactions, in which the symmetry of the unit is capitalised apon. Effectively, an eight-member ring anhydride is opened by the TSE protecting group, desymmetrizing the molecule and giving a free acid to couple to the pyrrole. This amide is then ready to participate in the group’s methodology.

In this reaction, it’s possible for the C-H activation to occur at either the C-2 or C-4 position – and on either side of the olefin. Impressively, the reaction gives a decent yield of the desired product (though from a thermodynamics POV, it seems to be the most likely outcome…?), using t-BuOOBz as the stoichiometric oxidant and the slightly-more-pokey-than-Pd(OAc)2 catalyst.

Completion of the target was relatively simple – hydrodge the nitro and alkene, remove the silyl groups with aluminium trichloride and use Mukaiyama’s reagent to close the lactam.

Beck, E.M., Hatley, R., Gaunt, M.J. (2008). Synthesis of Rhazinocine by a Metal-Catalyzed CH Bond Functionalization Strategy. Angewandte Chemie International Edition DOI: 10.1002/anie.200705005

InChiKey Dump:
TXWKUWXSHGUINF-IBGZPJMEBK JXMZUNPWVXQADG-UHFFFAOYAZ GRYWMWZQJYZJAB-UHFFFAOYAN PXGXZYIMQUQZIQ-UHFFFAOYAQ DOAOQEINYNDLQI-WNFQYIGGBP WLNWERXKIWCSAD-HHHXNRCGBR

1 Star2 Stars3 Stars4 Stars5 Stars (No Ratings Yet)
Loading ... Loading ...

11 Comments

  • Linker says:

    DOI links to the wrong paper, but is still interesting!

  • Handles says:

    hahah “meteorite catalyst”, I havent heard that one before :)

  • Phil says:

    Nice! I don’t want to imagine how much work went into this one-pot Suzuki, though.

  • Tot. Syn. says:

    Problem with the doi fixed. Damn copy&paste…

  • excimer says:

    Phil- the one-pot Suzuki has literature precedence (from one of the original papers on Ir CH activation)- see here

  • Eraser says:

    How about a post on the Axinellamines. Many groups are working on it, but Baran’s group is the first to complete a total synthesis (double publications available on Angewandte Early View)

  • wanderer says:

    waht does meteorite catalyst mean?

  • excimer says:

    Wanderer-

    Iridium is rarely found naturally in the Earth’s crust. Most of the iridium found on Earth is from meteorite impacts, as iridium is a common component of most meteorites. (Actually, it’s the presence of a large amount of iridium in a particular geologic band, the K-T Band, which dates to 65 million years ago, that is the strongest evidence of a meteorite impact as the source of the extinction of the dinosaurs.)

  • Rudolfin says:

    Please, if somebody has access to this magazine, I’ll need that sent this file to my by mail (Mail: soyformula21@hotmail.com)

    “Synthesis of Rhazinocine by a Metal-Catalyzed CH Bond Functionalization Strategy”, Elizabeth M. Beck 1, Richard Hatley, Dr. 2, Matthew J. Gaunt, Dr. ACIEE, 2008, EarlyView. DOI: 10.1002/anie.200705005.

    Thank you!!!

  • pmgb says:

    off-topic and personal, can you please add http://pmgb.wordpress.com/ to your blog roll and then delete this comment.

  • Diego says:

    meteorite catalyst, nice expression, the paper is great, too..