I’ve been meaning to write about this new synthetic organic chemistry paper, because it’s just so weird. That adjective probably needs a little explanation. The next few paragraphs will try to provide that; then we’ll get down to the paper itself.
Probably a good fraction of the readership here has had at least the sophomore-organic level of exposure to the field. Even if you haven’t, the landscape can be described in general terms. The different ways to form and break bonds in molecules fall into broad classes, and most organic chemistry classes are structured along those lines. If you try to memorize two semesters of organic chemistry as if it were a huge pile of random facts you are making a lot of unnecessary work for yourself. The reactions themselves fall into families whose actual mechanisms are conceptually related, and it’s a lot easier to keep track of things that way.
To pick one classic example, you can form a negatively charged carbon much more easily if it’s next to an electron-withdrawing group like a carbonyl or sulfonyl, for example, and those carbanions can go on to attack other “electrophilic” groups. So there’s a whole list of such reactions, many of which are named after 19th- and early-20th-century chemists, but they all start with carbon center that’s easily deprotonated, getting a full negative charge on it and turning around and reacting with functional groups that have more of a positive charge on one of their atoms.
There’s a big family of reactions that go through positively-charged carbons. Fully or partially charged oxygen and nitrogen atoms have their own things going. Outside of positive and negative charges, there’s a whole group of ring-forming cycloaddition reactions where several bonds’ worth of electrons sort of snap-snap-snap around in a circle (and some rearrangement reactions that work more or less the same way). There’s a big family of “free radical” reactions that involve single electrons on carbons and other atoms instead of the electron pairs you see in the charged mechanisms, and so on.
But what all this does is give an organic chemist a familiar landscape to work in. There are many transformations of molecules that (even if you’ve never seen them before), just look fairly sensible because of all the others you’ve learned. You’d maybe need a little time to draw the exact “arrow-pushing” mechanism of the reaction, but just looking at it you’re willing to believe that it’s OK.
And then there are some that just look bizarre. I’m a fan of those, because they promise stuff beyond the mental framework that I’ve gotten used to since I took sophomore organic back in ’81. When these appear, it’s like suddenly discovering while you’re driving that there’s a new shortcut road that you didn’t know about, one that connects two neighborhoods that you’ve always thought of as being far apart.
At right is the current bizarre reaction. Conceptually, it’s an amine deletion: an NH group is ripped out of a ring or chain and replaced by a new carbon-carbon bond. It’s safe to say that we haven’t had anything quite like that! It works through functionalizing the amine with a reagent that forms an N-N bond and then breaks down to an isodiazene, a rather exotic species that would then rather just turn into nitrogen gas and vamoose. When it does, it leaves behind free radicals on the two carbons that used to have the amine bonds, and those (doubtless shocked by this weird turn of events) gladly embrace each other to form the new C-C bond. Why yes, that is the way I tend to think about reaction mechanisms, why do you ask?
As the authors note, this means that a wide-ranging amine-forming reaction like reductive amination can now serve as a precursor step for a carbon-carbon bond forming reaction. That means a lot, because making amines is relatively easy, while making C-C bonds is relatively hard. The reaction seems to be very tolerant of other functional groups in the molecule, which is good news. You do want to have radical-stabilizing groups on at least one of the two carbons involved, ideally.
My first thought on seeing this reaction was that I wished it ran (conceptually) in the opposite direction: I would very much like something that turned an alkane chain into a secondary amine, or a cyclopentane into a piperidine. But the more I think about this one, the more it grows on me. There are some carbon frameworks that are going to be a lot easier to get to via this route than by any others, and a lot of diversity than can come in via amine-forming reactions between a variety of partners. I hope I can get the chance to try out this transformation with my own hands!