Comparative diastereoselectivity analysis of crotylindium and 3-bromoallylindium additions to alpha-oxy aldehydes in aqueous and nonaqueous solvent systems

The couplings of crotyl bromide (1) and 1,3-dibromopropene (2) to a triad of conformationally unrestricted a-oxy aldehydes in water, aqueous THF (1:1), and anhydrous THF are described. In no example involving 1 was the formation of anti,syn product detected. The proportion of syn isomers reached a maximum (syn/anti = 5.6:1) when the neighboring hydroxyl group was unprotected and water was the reaction medium. Although internal chelation also operates to some degree with 2, considerable erosion of this mechanistic pathway (maximum now only 2:1) in favor of Felkin and ''anti-Felkin'' transition states is reflected in the product distributions. This trend can be synthetically advantageous, and a utilitarian example is demonstrated. The indium reagents studied here are notably efficient nucleophilic reaction partners in water.