Direct Synthesis of Polysubstituted Aluminoisoxazoles and Pyrazoles by a Metalative Cyclization

Olivier Jackowski (1) , Thomas Lecourt (1) , Laurent Micouin (2)

1 SSMIP - Synthèse et structure de molécules d'interet pharmacologique
2 LCBPT - UMR 8601 - Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques

Alumino-heteroles are obtained from simple precursors in a fully chemo-and regioselective manner by a metalative cyclization. The carbonÀaluminum bond is still able to react further with several electrophiles, without the need of transmetalation. This synthetic route provides a novel entry to heterocyclic organoaluminum reagents as well as a straightforward access to 3,4,5-trisubstituted isoxazoles and 1,3,4,5-tetrasubstituted pyrazoles. The preparation of main-group aryl and heteroaryl organometallics is a very active field, as these reagents are key intermediates in diversity-oriented elaboration of compounds for pharmaceutical and material science applications. 1 In this context, the preparation of aryl-or hetero-cyclic organoaluminum reagents has gained a renewed interest , due to their potential broad functional tolerance 2 and the low cost and toxicity of alanes. 3 A conventional preparative method for aromatic orga-noaluminum compounds has been the transmetalation of the corresponding lithium or magnesium derivatives with various aluminum(III) sources, 4 or in some cases trough aluminumÀtin or boron exchange reactions. 5 However, the transmetalation pathway, generally conducted at low temperature from reactive organolithium reagents, 6 generates salts as side products. These salts have been reported to strongly affect the reactivity 7 of the final organoalumi-num reagent and the enantioselectivity of asymmetric processes. 8 This procedure is very often conducted in ethereal solvents, known to strongly decrease the Lewis acidity of organoaluminum reagents and, therefore, to affect their reactivity. Finally, the potential functional group tolerance of the carbonÀaluminum bond cannot be exploited if (1) (a) Handbook of Functionnalized Organometallics; Knochel, P., Ed.; WILEY-VCH: Weinheim, 2005. (b) Chinchilla, R.; Najera, C.; Yus, M.

Domaines: Chimie organique

Olivier Jackowski, Thomas Lecourt, Laurent Micouin. Direct Synthesis of Polysubstituted Aluminoisoxazoles and Pyrazoles by a Metalative Cyclization. Organic Letters, 2011, 13 (20), pp.5664-5667. ⟨10.1021/ol202389u⟩. ⟨hal-02185376⟩