Palladium-catalyzed allylic amination using aqueous ammonia for the synthesis of primary amines

Abstract

Allylic amination catalyzed by palladium complexes is a common method for the preparation of allyl amines. Despite the diverse nitrogen nucleophiles that undergo this chemical transform, the use of ammonia for allylic amination to yield primary amines has not yet been reported. This observation is fortified by authoritative review articles, which consider ammonia to be unreactive or an ineffective nucleophile for π-allylpalladium amination. Nevertheless, the use of ammonia to directly access primary allylic amines is appealing on the basis of cost and atom economy. Interestingly in this work, 1,3-diphenylallyl acetate (1) was fully converted to produce primary amine 2a along with secondary amine 3 using aqueous ammonia in the presence of catalytic amount of Pd(PPh 3)4 at room temperature (Scheme 1). It is noteworthy, however, that ammonia gas failed to deliver the product under similar conditions. Encouraged by these results, the reaction of 1 was optimized as detailed in Table 1. Increasing the NH3/THF ratio (entries 1 and 2) and dilution (entries 2-4) improved the selectivity, whereas the use of nonpolar toluene failed to produce the products (entry 6). Additionally, polar aprotic solvents gave comparable results (entries 5-8). Remarkably, among the solvents tested, 1,4-dioxane provided the best efficiency. The 0.04 M concentration was optimum because further dilution resulted in no reaction (entries 9-12), probably due to deactivation of Pd(0) upon liberation of phosphine ligands. Using the optimized conditions, the scope of the reaction was explored using a variety of substrates (Table 2). Entry 2 shows that 1,3-dialkyl allyl acetate is also amenable to this reaction, yielding primary amine 2b. The (Chemical Equation Presented) cyclic allyl carbonates with diverse substituents (entries 3-8) and the five-and seven-membered cyclic substrates (entries 9-11) gave the respective primary amines in high yields and excellent selectivities. Finally, the asymmetric variant of this reaction (Scheme 2) also proceeded smoothly to afford primary amine in good yield and high enantioselectivity. (Table Presented) © 2010 Data Trace Publishing Company.