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 modern 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.1 Catalytic amounts of structurally complex and difficult to obtain pyridine-N-oxides have been recently used as organic Lewis bases capable of promoting the enantioselective allylation of aldehydes.2 A very short and easy entry to chiral pyridine-N-oxides was envisaged in the reaction between 2-pyridinecarboxylic acid N-oxide and commercially available, enantiomerically pure diamines. A family of N-oxides (1) was thus prepared in moderate to good yields (Scheme 1). A second family of N-oxides (2) was prepared by bis esterification of 2-(6,6’-dihydroxyphenil)-3-methyl pyridine-N-oxide with readily available enantiomerically pure carboxilic acids. 1H-NMR studies revealed that the catalysts have a strongly preferred conformation and thus stereochemically defined 3-D structures. Scheme 1 The catalytic activity of these N-oxides was tested in the reaction of benzaldehyde with allyltrichlorosilane affording the homoallylic alcohol. Among the catalysts employed, bis pyridine-N-oxides (1) afforded the desired product in up to 60% yield and up to 50% ee; mono pyridine-N-oxides (2) performed better in terms of stereoselectivity (up to 45% yield, up to 68% ee). The use of both types of catalysts 1 and 2 was extended to other aromatic aldehydes, bearing both electron-withdrawing and electron-donating substituents, affording homoallylic alcohols in up to 73% yield and 37% ee for catalysts of type 1 and up to 60% yield and 84% ee for catalysts of type 2.