Pyridine- N-Oxides as New Organocatalysts for the Enantioselective Allylation of Aldehydes

Enantioselective organic catalysis represents one of the most rapidly expanding fields of research in organic chemistry. The term “organic” emphasizes the advantages of performing a catalytic reaction under metal-free conditions, exploiting substoichiometric amounts of a small organic molecule which is often more stable and cheaper than its organometallic equivalent. Catalytic amounts of of-ten structurally complex pyridine and amine N-oxides have been recently used as or¬ganic Lewis bases capable of promoting the enantioselective allylation of aldehydes.1 Our work was aimed to develop simpler and easier-to-prepare chiral N-oxides: some new families of chiral pyridine and amine N-oxides were synthesized and tested in the reaction of aro¬matic alde-hydes with allyltrichlorosilane affording the corresponding homoallylic alcohols (Figure 1). Figure 1 The N-oxide shown in Figure 2, easily prepared from 2-(6,6’-dihydroxyphenyl)-3-methylpyridine and N-Cbz-(S)-proline, gave the best results in terms of stereoselectivity (up to 84 % e.e. and up to 60 % yield).2 Figure 2 We then prepared and tested in the allylation reaction several structurally modified pyridine N-oxide derivatives, in order to shed light on some as¬pects of the reaction mecha¬nism (e.g. the chelation of the silicon atom by electron-donor atoms of the cata¬lyst) and possibly im¬prove the stereose¬lectivity. Although the expected im¬provement was not observed, we could better understand the reaction mechanism and develop a model of stereo¬selection.