Dr. Freddy probably said it best: Please, slow down, Phil!
|Source: JACS ASAP|
The group ID's a logical starting point: sclareolide, an essential oil isolated from various species of sage plants. Long story short - the first few avenues (iodination, carboxylate degradation, BF3 salts) are all dead ends. The "Eureka!" moment comes when they try a cyclic borole (see right), which succeeds on multigram scale and produces a med-chem-friendly crystalline white solid. Using increasingly-popular radical conditions, Baran's team readily attaches this intermediate to benzoquinone (46-60% yield).
The result? A natural product, (+)-chromazonarol, formed in 34% yield... in only six steps! Mere mortals might have called it a day, but not Dr. Phil: he goes on to make nine more natural products, most of which had previously taken >12 steps to make on their own...not too shabby for a four-page Communication.
|Boroles: All the things I've|
come to remember...
Source: 1000 Eighties Blog