Hydroamination of Alkynes Catalyzed by Palladium/Benzoic Acid

Abstract

The reaction of internal alkynes (1) with amines (2) in the presence of catalytic amount of Pd(PPh 3 ) 4 and benzoic acid in dioxane at 100ºC gave the allylic amines (3) in good to excellent yields.The intramolecular reaction of alkynes with tethered amino groups (4) gave 2-vinylpyrrolidines and 2-vinylpiperidines (5) in good to excellent yields.The carbon-nitrogen bond is frequently encountered in fragments of various biologically active natural products.Hence, the development of efficient synthetic approaches leading to nitrogen based compounds is a subject of considerable attraction.The organometallic reactions involving the formal addition of a N-H bond across a carbon-carbon multiple bond appear to offer the most attractive route to such compounds, because this process does not generate byproducts generally observed in the metal-catalyzed substitution process.1 The palladium-catalyzed intermolecular hydroaminations of 1,3-dienes, 2 allenes, 3 enynes, 4 and methylenecyclopropanes 5 have been developed to realize the ideal carbon-nitrogen bond formation.On the other hand, we have previously reported that certain alkynes react with carbon pronucleophiles in the presence of palladium/acetic acid catalyst to give the corresponding allylation products. 6This hydrocarbonation is similar to the hydroacylation process reported by Trost et al. for the allylation of acetic acid with alkynes which gives allylic acetates. 7The utility of this methodology prompted us to extend the formal hydrocarbonation to the formal hydroamination to provide a new atom-economical procedure for the synthesis of amines from alkynes. 8In fact, the reaction of certain acetylene derivatives (1) with amines (2) in the presence of 5 mol% Pd(PPh 3 ) 4 and 10 mol% PhCO 2 H in dioxane at 100ºC gave the corresponding allylic amines (3) in very high to good yields (eq.1).We describe herein an account of our results, part of which has been reported previously.