The main synthetic use of Weinreb amides derives from their reactivity toward nucleophiles. They can be useful for the addition of Grignard or alkyllithium reagents to produce ketones. Other advantages are seen in the selective reduction of the Weinreb amides to the corresponding aldehydes. The chelation ability of the amides provides a stable intermediate that does not form the aldehyde until aqueous workup. This prevents the overreduction commonly seen with other functionalities. Several reviews and numerous articles on the utility of Weinreb amides have been published (13, 14, and references therein).

Many methods exist to generate Weinreb amides from a variety of starting materials. An example is the simple treatment of an acid chloride and an N,O-dimethylhydroxylamine hydrochloride at 0 °C with 2.2 equiv of pyridine (12). Methods to generate the amides from carboxylic acid precursors also can be carried out by using conventional coupling reagents such as (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) (15), dicyclohexylcarbodiimide (16), and others (17, 18).

Our laboratory has made progress in this area using bis(methoxyethyl)aminotrifluorsulfur, the Deoxo-Fluor reagent (Air Products and Chemicals, Allentown, PA) (19). This reagent provides a general one-pot procedure to generate the corresponding amides with relatively few byproducts, which are often a problem with some of the previously used coupling reagents. Boc is tert-butoxycarbonyl. Furthermore, no racemization is seen when an -chiral center is present, because of the known -hydrogen stability with acyl fluorides. The Deoxo-Fluor procedure provides an additional route to generate chiral Weinreb amides. Further investigation in this area is under way.