Interesting Inter/Intramolecular Cycloadditions November 21, 2006Posted by thwalls in Synthetic Chemistry.
I’m sure that most of you are aware of the [4+2] cycloaddition known as the Diels Alder reaction and if you’re not then you should probably pick up that Organic I textbook and turn to the chapter on pericyclic reactions for dummies. Well, some interesting work caught my eye (mostly because I was trying to figure out some problems of my own) from the Boger Lab at Scripps. For several years now he and his have been working on the preparation of vinca alkaloids by way of an intramolecular Diels-Alder/1,3-Dipolar Cycloaddition cascade. A good discussion of this work was published very recently in JACS (J. Am. chem. Soc. 2006, 128, 10589-10595) and i suggest thatif your not living under a rock you should check it out.
Anyway, in the aformentioned article it discusses the use of this [4+2]/[3+2] tandem reaction to set 6, count em, 6 stereocenters in one step. Well, actually there are two steps but the intermediate is so strained that it does not exist for very long. The reaction starts with a 1,3,4-oxadiazole and is electron deficient which sets up the first step of running the inverse electron demand DA reaction by using an electron rich dienophile. The product of this step being a strained cycloadduct that imediately loses Nitrogen and leaves a carbonyl ylide. This undergoes a 1,3-dipolar addition with a second mole of olefin (which is either electron rich or strained and can be cyclic) to form the oxa-bicyclo-[2.2.1]-heptane product.
Regardless of its usefulness for anything other than alkaloid products, such as Vindoline (J. Am. Chem. Soc. 2002, 124, 11292-11294), it makes me smile because six stereocenters, controlling stereo- and regiochemistry, is always something to dance to.
So there you go, my first donation to the land of the chemically inclined. But I won’t rant and rave about all the chemistry involved, if you want to know more, open Scifinder Scholar and pretend its reading rainbow.