Palladium‐Catalyzed Intermolecular Aerobic Oxidative Amination of Terminal Alkenes: Efficient Synthesis of Linear Allylamine Derivatives

Abstract

Dedicated to Professor Xiyan Lu on the occasion of his 80th birthdayThe rich variety of nitrogen-containing molecules that occur as natural and synthetic products has inspired considerable interest in the development of new methods for their syntheses.[1] Among the strategies involving the direct amination of olefins by CÀN bond formation, [2][3] the synthesis of amine derivatives by intermolecular dioxygen-coupled oxidative amination of olefins is particularly attractive. [4][5][6] Palladium-catalyzed methods for intermolecular aerobic oxidative amination of unactivated olefins, known as azaWacker reactions, have been recently reported to yield enamide derivatives (Scheme 1, left arrow).[2e, 4, 6] These reactions are proposed to proceed by Markovnikov aminopalladation of the alkene with subsequent bhydride elimination, resulting in the functionalization of the olefin at the C2 position. Herein we describe a new method for intermolecular dioxygen-coupled oxidative amination of unactivated olefins under cocatalyst free reaction conditions, which affords linear allylic amine derivatives with high regioselectivity (Scheme 1, right arrow). [7][8][9][10] These reactions appear to proceed by allylic CÀH activation and subsequent nucleophilic attack at the C1 position of an intermediate pallylpalladium species. We initiated the search for allylic amination reactions by examining the reaction of 1-undecene (1 a) with nitrogen nucleophiles having an acidic NH group.[11] Dimethylacetamide (DMA) was selected as the solvent because it was shown to be the most effective solvent for aerobic allylic acetoxylation of alkenes.[7c] Treatment of phthalimide and 1 a with Pd(OAc) 2 under a dioxygen atmosphere (6 atm) in the presence or absence of the basic resin D301 (OH) [12] afforded oxidative amination products exclusively associated with azaWacker-type reactivity; the products were enimide 3 and various alkene isomers (Scheme 2). No allylic amination products were observed. The reaction of tosylamide and Nmethyl tosylamide did not form any amination product. The use of saccharin as the nucleophile, however, resulted in highly regioselective linear (E)-allylic amination products (2) and the corresponding alkene isomers (Scheme 2). Optimal results were obtained when the reaction was performed in the presence of maleic anhydride (MA) and 4 molecular sieves (see the Supporting Information Table-S1 for details), which led to a 95 % yield of the oxidative allylic amination product with respect to saccharin. Only linear amination products (C1 amination) were obtained; neither the enimide (C2 amination) nor the branched allylimide (C3 amination) was detected. The yield decreased to 78 % under 1 atmosphere of dioxygen, and the use of N-methylpyrrolidinone (NMP) or N,N-dimethylformamide (DMF) instead of DMA, gave a slightly lower yield. A very low product yield (ca. 10 %) was obtained with dimethylsulfoxide (DMSO) as the solvent. Scheme 2. Pd-catalyzed the aerobic oxidative amination of 1-undecene (1 a) with phthalimide and saccharin.

O 2 -promoted allylic acetoxylation of alkenes: Assessment of “push” versus “pull” mechanisms and comparison between O 2 and benzoquinone

“…10 Liu and coworkers achieved aerobic allylic imidation under similar conditions by employing 40 mol % of maleic anhydride as an additive in the reaction (eq 2). 11 Finally, we reported that use of 4,5-diazafluorenone as an ancillary ligand enables aerobic allylic acetoxylation of alkenes under 1 atm O 2 (eq 3). 12 …”

Aerobic Linear Allylic C–H Amination: Overcoming Benzoquinone Inhibition

“…O 2 or air). 12,13 Significant amounts of double bond isomerization in both the starting materials and products (up to 50%) necessitate the use of large excesses of olefin and limit applications in fine chemical synthesis. 12–14 …”

“…It is significant to note that these preparative conditions contrast those of previously reported aerobic allylic C—H amination methods ( vida supra ). 12,13 …”

Palladium Complex Bearing 3,5-Bis(benzotriazol-1-Ylmethyl)toluene Ligand Catalyzes Oxidative Amination of Allyl Butyl Ether

“…This assumption is supported by the presence of one band at 350 cm -1 in the infrared spectrum, assigned to the stretching frequency of the Pd-Cl bond, which is characteristic of a trans dichloride isomer. 40 Considering that a variety of palladium(II) complexes have been successfully studied as catalysts in oxidative amination of alkenes reactions, [25][26][27][28][29][30][31][32][33][34][35][36][37] we tested the behavior of complexes 2 and 3 in the reaction of phthalimide with allyl butyl ether.…”

“…24 On the other hand, a variety of palladium(II) complexes have been successfully studied as catalysts for the aerobic oxidative amination of unactivated alkenes to yield amine derivatives. [25][26][27][28][29][30][31][32][33][34][35][36][37][38] This catalytic reaction leads to the formation of imines or enamines, via b-hydride elimination, through a mechanism analogous to the well-known Wacker process. 25 In this communication we report the synthesis and characterization of the new ligand 3,5-bis(benzotriazol-1-ylmethyl)toluene (1) …”