The Good Samarium

Samarium iodide, for some strange reason, used to be one of those inorganic reagents that I would just skip over while reading organic synthesis or methods papers. I can’t really say why; I mean, it’s a simple reagent, and as you might expect of simple reagents, it has a fairly simple function: it’s a one-electron reducing agent.

That said, a wealth of interesting chemistry has come out of this simple function. Samarium is quite oxophilic, so enolates of samarium often react with great stereoselectivity, particularly in intramolecular processes. Samarium enolates figure prominently in the Reformatsky reaction, the addition of beta-halide esters (or lactones) to carbonyls. Among strictly reductive applications, sulfones can be reduced to sulfides in the presence of carbonyls, and alkyl halides can be chewed up to alkanes. Carbonyls can be reduced as well.

Perhaps the most useful reaction involving SmI2 is the Barbier reaction, essentially a one-pot Grignard reaction of an alkyl halide with a carbonyl. Take a solution of your alkyl halide, dump in some SmI2, add the carbonyl compound, and abracadabra, carbonyl addition. The intramolecular Barbier reaction presents a mechanistic conundrum: how does SmI2 end up inserting into the alkyl halide bond without reducing the necessarily close carbonyl group? And if the carbonyl does get reduced, what happens? Mechanistic studies of the Barbier reaction are, needless to say, a little murky.

One-electron reduction of electrophilic substrates opens the door to a huge area of research. In fact, there’s another name for it…radical chemistry! One-electron reduction of halides leads to organosamarium intermediates that act like radicals, which can then react with alkenes, alkynes, etc. Radical cyclizations involving SmI2 are quite common. An Org. Lett. ASAP by Proctor and crew demonstrates the use of samarium iodide for spirocyclizations of cyclic unsaturated amides.Initial reduction of the enone leads to a radical anion, which picks up a proton from methanol to generate an enol radical, which is reduced again at oxygen to generate a samarium enolate. Chelation of the other carbonyl group to samarium leads to stereoselective carbonyl addition, generating a spiro center at the enolizable carbon. Key here is the selective reduction of the enone over the ketone–SmI2 is also well known for its precise functional group selectivity.

I couldn’t possibly cover samarium iodide chemistry exhaustively in one post, so here’s a review for the curious. Perhaps readers could shed some light by commenting…? 🙂

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2 Comments

  1. Samarium diiodide is one of those skill-based reagents (well, according to my PI). It’s so damn oxygen senstive that you need to freeze-pump-thaw like a mofo to ensure it’s anoxic (sparging may not work). Shows the amazing-ness of Molander’s research group. Tschenko reductions are highly overrated; tandem Barbier-Grob is the way to be.

    P.S. Love the Buddy Christ. Doesn’t it just pop, “Buddy Christ?”

    Reply

  2. Word, dogma is one of my favorite movies ever.

    What exactly is sparging? I pretty much lived next to a vac line during undergrad, but I’ve never heard of sparging (probably because all the reactions I did were strictly oxygen-free)…

    Reply

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