Monday, June 29, 2015

(Please) Make More Molecules using Light!

Update (6/29) - Commenters chime in with some notables I'd mistakenly left off the list. I'll append their molecules to the end of this post (vide infra)...

I'm officially calling it: Photoredox catalysis = the new "it reaction" for organic chemistry.

Like many before it - iron catalysis, the gold rush, anything palladium, organocatalysis - photoredox catalysis is now appearing in my RSS feed on a near-hourly basis. We're in the early days of an exciting field; I've noticed more methodology papers and mechanistic studies lately. Assuming you start with a suitable aryl halide, diazonium, or carboxylic acid, the synthetic toolkit of single-electron catalysis seems virtually limitless.

Which begs the question . . .where are all the photoredox total syntheses?

Three examples of recent total syntheses that capitalize
on photoredox catalysis (bonds in red)
SciFinder: "photoredox total synthesis?"
7 hits.

How about "light-mediated total synthesis?"
7 more.

One more try: "photoredox natural products?"
7 hits.

Most of these hits actually lead to conference abstracts, not individual manuscripts. Props to the Stephenson group (Michigan), who leads the charge with syntheses of aspidosperma alkaloids and gliocladin C. Based on SciFinder results, I'd include the MacMillan synthesis of Lyrica, and Lei's isoquinoline syntheses from JOC.

Readers, what am I missing? A pivotal review or book? A group whose research is at the forefront of solar-powered natural product production? Perhaps a major non-English journal article? Any examples where a venerable old lion of total synthesis utilized a photoredox reaction alongside their Diels-Alders and aldol reactions?

For such a large-upside field, it sure seems quiet out there.
--
Update: Molecules made with photoredox catalysis, as suggested by my beloved commenters:

Overman, (-)-aplyviolene, Ru(bpy)3
MacMillan, fenofibrate (OK, not a np), Ni(II), Ir(III)
MacMillan, (-)-burshernin, Ru(bpy)3
Nicewicz, methylenolactocin and Protolichesterinic Acid, acridinium
Nicewicz, magnosalin + pellucidin A
Yoon, heitziamide A, Ru(bpz)3
Yoon, epiraikovenal, Ir(III)
Chen + Baran, sceptrin, Ir(ppz)3
Chen, nakamuric acid, Ir(ppy)3
Lawrence / Sherburn, endiandric acid A, kingianins A,D,F, kingianic acid E, Ru(bpy)3
Carreira, (+)-Daphmanidin E, Co-diimine (method here)

More?

9 comments:

  1. How about Overman?
    http://onlinelibrary.wiley.com/doi/10.1002/anie.201204977/abstract

    ReplyDelete
  2. and while I'm thinking about it, pretty sure Macmillan made some nat prods in his two most recent nickel/photoredox papers

    ReplyDelete
  3. Besides MacMillan and Stephenson, some of the other groups in this field have also published natural product syntheses using their chemistry, though usually as a highlight at the end of a methods paper. For example:

    Nicewicz: http://pubs.rsc.org/en/content/articlelanding/2013/sc/c3sc50643f#!divAbstract
    http://pubs.acs.org/doi/abs/10.1021/ol5022993

    Yoon: http://pubs.acs.org/doi/abs/10.1021/ja2093579
    http://onlinelibrary.wiley.com/doi/10.1002/anie.201204835/abstract
    http://onlinelibrary.wiley.com/doi/10.1002/anie.201406393/abstract
    http://onlinelibrary.wiley.com/doi/10.1002/anie.201405359/abstract

    Chen: http://www.sciencedirect.com/science/article/pii/S0040402014014549
    (w/ Baran): http://www.sciencemag.org/content/346/6206/219.abstract

    For a venerable old lion of total synthesis, how about Overman? His group has recently applied photoredox catalysis to generate sterically congested tertiary radicals for conjugate additions. A few examples: http://onlinelibrary.wiley.com/doi/10.1002/anie.201204977/abstract
    http://pubs.acs.org/doi/abs/10.1021/ja512527s
    http://pubs.acs.org/doi/pdf/10.1021/acs.joc.5b00794

    It's important to remember that many of the reactive intermediates people are generating are not new things. There are plenty of examples in the literature of making these using (1 electron) chemical oxidants and reductants and/or electrochemical setups, and these strategies have even found their way into natural product syntheses (for a minireview, see: http://onlinelibrary.wiley.com/doi/10.1002/ejoc.201101071/abstract). Photoredox catalysis offers the benefit of operational simplicity, commercially-available reagents, no mercury arc lamp, etc., but much of the underlying chemistry has been studied before. That said, there may be unexplored advantages to the photoredox approach. I remember hearing MacMillan give a talk where he emphasized how photoredox catalysis enabled slow generation of the reactive species (IIRC, he called it "the world's smallest syringe pump") and thereby avoided a lot of homocoupling or deactivation that plagued traditional, stochiometric methods.
    Exciting chemistry, no doubt.

    ReplyDelete
    Replies
    1. Thanks for this well-thought, well-organized reply!
      I've updated the post based on all the fantastic feedback.

      Delete
  4. speak of the devil, DMac's got another in this one that came out today

    http://onlinelibrary.wiley.com/doi/10.1002/anie.201503789/abstract;jsessionid=46BA5FAE28680850AA97A3548BE962A9.f04t03

    ReplyDelete
  5. A recent application of Yoon's Ru(bpy)3 photoredox catalysis in total synthesis:

    kingianic acid E: Sherburn/Lawrence, Chem Sci, 2015 http://pubs.rsc.org/en/content/articlepdf/2015/sc/c5sc00794a

    Could the famous endiandric acids be products of visible light mediated formal Diels-Alder reactions in Nature?

    ReplyDelete
  6. Method:
    http://onlinelibrary.wiley.com/doi/10.1002/anie.201105235/abstract
    Application:
    http://onlinelibrary.wiley.com/doi/10.1002/anie.201104681/abstract

    ReplyDelete
  7. heyrovsky's ghostJuly 06, 2015 2:38 PM

    I'm disappointed with the lack of rigorous electrochemistry involved here. Would love to see more organic labs teaming up with electroanalytical folks to better interrogate these reactions. There's a whole universe of black magic electrochem out there. It would be a real shame to see the field go for a hack and slash approach instead of leveraging existing expertise.

    ReplyDelete
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