Two-group disconnections are better than one-group disconnections
المؤلف:
Jonathan Clayden , Nick Greeves , Stuart Warren
المصدر:
ORGANIC CHEMISTRY
الجزء والصفحة:
ص702-703
2025-07-10
409
This compound was needed for some research into the mechanisms of rearrangements. We can disconnect on either side of the ether oxygen atom, but (b) is much better because (a) does not correspond to a reliable reaction: it might be hard to control selective alkylation of the primary hydroxyl group in the presence of the secondary one.
You might think that the best reagent to use as the equivalent of the synthon B would be bromide C. Be more ingenious! A much better solution is to use the epoxide D. Nucleophilic attack on the less hindered terminal carbon atom of the epoxide gives us the type of com pound we want, and this was how the target molecule was made. In using the epoxide we have gone one step beyond all the disconnections we have talked about so far because we have used one functional group to help disconnect another—in other words, we noticed the alcohol adjacent to the ether we wanted to disconnect and managed to involve them both in the disconnection. Such disconnections are known as two-group disconnections, and you should always be on the look-out for opportunities of using them because they are an efficient way of getting back to simple starting materials. We call this epoxide disconnection a 1,2-disconnection because the two functional groups in the two-group disconnection are in a 1,2-relationship.
Drug molecules often have 1,2-related functional groups: 2-amino alcohols form one important class. Phenyramidol, for example, is a muscle relaxant. A simple two-group disconnection takes it straight back to 2-amino pyridine and styrene oxide.
Notice that we have written ‘1,2-diX’ above the arrow to show that it’s a two-group (‘diX’) disconnection—we’ve also numbered the carbon atoms in the starting material to show the 1,2-relationship. It may seem trivial in such a simple example, but it’s a useful part of the process of writing retrosynthetic analyses because it helps you to spot opportunities for making two-group disconnections.
الاكثر قراءة في مواضيع عامة في الكيمياء العضوية
اخر الاخبار
اخبار العتبة العباسية المقدسة
