Rhodium (posted 10-15-98)
--------------------------------
The yields are probably pretty low when using the olefin, but shouldn't they be much improved if using a halosafrole instead?
drone 342 (posted 10-16-98)
----------------------------------
That's exactly what I originally thought, though LR believes that due to some acidity of the benzylic protons, a strong base like lithium amide or lithium methylamide is going to catalyze the formation of isosafrole.
Originally, what got me thinking in this direction was the Sn2 reactions (which is what you're proposing), can be greatly improved kinetically by two ways: getting a better leaving group, and by using a stronger base. Iodine is about as good as you can do clandestinely for a leaving group (if you can think of a better one, say so), but the base (ammonia or methylamine) could use a little tweeking. By using a metal amide (pKa is around 45), you're gonna have a very fast, very nice reaction. However, a side reaction that may happen is the abstraction of the benzylic proton, followed by the leaving of the halide, resulting in isosafrole.
There is a lot of reason to believe this is the case; there are examples in the literature where a strong base did this to safrole-based compound. However, I still remain somewhat skeptical that this cannot be avoided. I still believe reasonable conditions exist where this side-reaction scenario would hardly occur, and the result would be a very high-quality final product in good yields.
-drone #342
Quoted fromPost 122758 (https://www.thevespiary.org/talk/index.php?topic=12285.msg12275800#msg12275800)
(dormouse: "Grignard reagents and methylenedioxy rings", Serious Chemistry)