I am just reading the Tetrahedron report number 800 on "Titanium carbenoid reagents for converting carbonyl groups into alkenes" by Hartley and that reminds me a paper of Nicolaou, I read some years ago, concerning the reaction of Titanocene methylidene with isoquinoline N-oxide.
In his paper, KCN noticed that the different "pyridine" N-oxides can be deoxygenated by Tebbe reagent and in the same time the introduction of a methyl group in also possible (in alpha of the N), and regioselectively in the case of isoquinoline. The same reactivity has been observed with Petasis reagent, but with longer time reaction and higher temperature.
Angew. Chem. Int. Ed. 2000, 39, 2529.
In his paper, KCN noticed that the different "pyridine" N-oxides can be deoxygenated by Tebbe reagent and in the same time the introduction of a methyl group in also possible (in alpha of the N), and regioselectively in the case of isoquinoline. The same reactivity has been observed with Petasis reagent, but with longer time reaction and higher temperature.
Angew. Chem. Int. Ed. 2000, 39, 2529.
4 commentaires:
Thats a sweet transformation...but what drives the regioselectivity? at the more hindered centre?
The regioselectivity is the same as the N-alkylated isoquinoline, the quaternization of the N enhances the reactivity toward aromatic nucleophilic substitution (in fact Addition-Elimination process) on the carbons C1 and C3, but according to calculations both charge density and FMO theory (I don't have the values in mind), the nucleophilic attack is on C1. Concerning the hinderence, the attack is not in the plane of the isoquinoline, I don't know the angle, but it should be close to 90°, so a H is not enough, even a t-Bu in C8 should not be big enough to reverse the reactivity.
Isoquinolines love Nu addition in the 1 postion. You can take the the parent isoquinoline (or quinoline for that matter) and add a strongly nucleoiphilic organometallics like RLi or RMgX, but you have to re-aromatise the resulting 1,2-dihydro addition product by some oxidant at the end.
Il semble que vous soyez un expert dans ce domaine, vos remarques sont tres interessantes, merci.
- Daniel
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