Ode to the Joy of Electrophilic Bromination

I think it’s strange that my favorite Beethoven symphony (Number 9, Number 9… ) is played around Christmastime. Additionally, this may not seem a propitious place from which to launch into a discussion of enzymatic bromination. And you would be right. Except that in both cases, I don’t really know what’s going on. Ode to Joy isn’t really religious and has nothing to do with snowmen or chestnuts or open fires. (Plus I don’t speak German. But I do hear that the translation is festive!)

In a similar way, we scientist types have only guesses as to how enzymes perform brominations. We think haloperoxidases mostly involve vague electron-pushing around peroxides, bromine anions, and metals (Fe or Mn) to make hypohalous acids, but beyond that… well… we dunno.

And uh I quote:

“Although a large number of halogenated organic compounds have been isolated, not much is known about the mechanisms by which fluorine, chlorine, bromine, or iodine atoms are incorporated into organic compounds.” [1]

Regardless of whether that was a horrible analogy, we do know much about electrophilic bromination in other contexts. For example, standard bromination conditions in organic chemistry commonly use NBS or bromine, and their mechanisms are well understood (think like Sophomore Organic Reactions) level of understanding). Hopefully someone can fill in the blanks someday with enzymatic halogenation. Although, it might be possible an understanding of Fenton chemistry would help… hmm. I’m certainly not an expert in this field, but I’d love to hear from someone who is!

[1] van Pee, K.-H.; Unversucht, S. Chemosphere 2003, 52, 299–312.

Biosynthesis of Terpenes

Molecules have a beauty and simplicity and belies their importance and efficacy. My inspiration in chemistry was reading the aptly named Atkins tome Molecules, a book that fascinated me to no end. Really, ad infinitum.

Life begins with geranyl diphosphate. “O-P-P!” as I say it. To get most of the essential oils, some oxidation or rearrangement needed. btw, not all arrows were created equal.

The really interesting part is that the selective oxidation is something that chemists can do, we don’t have to rely on magic enzymes (they’re really not that magical – just have about a billion years of evolution more expertise. same difference). As a practical matter, chemists are mostly concerned with chemoselective oxidation to do this.. Hydrocobaltalation of myrcene, followed by exposure to heat and triplet oxygen can give linalool peroxide, which can then be reduced to linalool. Old school reference! I hope there are easier ways to do this chemistry. Racemic product by the way!

Next time: electrophilic bromination!