An Efficient Method for the Selective Iridium‐Catalyzed Monoalkylation of (Hetero)aromatic Amines with Primary Alcohols

Abstract

An efficient multi-gram scale synthesis protocol of a variety of P,N ligands is described. The synthesis is achieved in a two-step reaction. First, the amine is deprotonated and subsequently the chlorophosphine is added to yield the corresponding P,N ligand. Deprotonation of the amine is normally achieved with n-BuLi at low temperature, but for the preparation of ligands with a 2,2'-dipyridylamino backbone and phosphines with a high steric demand KH has to be employed in combination with reaction temperatures of 110 8C for the salt metathesis step. The reaction of two equivalents of a selected P,N ligand with one equivalent of the iridium complex [IrClA C H T U N G T R E N N U N G (cod)] 2 (cod = 1,5-cyclooctadiene) affords P,N ligand-coordinated iridium complexes in quantitative yield. X-Ray single crystal structure analysis of one of these complexes reveals a monomeric five-coordinated structure in the solid state. The iridium complexes were used to form catalysts for the N-alkylation of aromatic amines with alcohols. The catalyst system was optimized by studying 8 different P,N ligands, 9 different solvents and 14 different bases. Systematic variation of the substrate to base and the amine to alcohol ratios as well as the catalyst loading led to optimized catalytic reaction conditions. The substrate scope of the developed catalytic protocol was shown by synthesizing 20 different amines of which 12 could be obtained in isolated yields higher than 90%. A new efficient catalyst system for the selective monoalkylation of primary aromatic and heteroaromatic amines with primary aromatic, heteroaromatic as well as aliphatic alcohols has been established. The reaction proceeds with rather moderate catalyst loadings.

Efficient and Clean Gold‐Catalyzed One‐Pot Selective N‐Alkylation of Amines with Alcohols

“…Until now, reports are largely focused on Ru- [5] or Ir- [6] based homogeneous systems, which are not practically useful because of the problem of reusability and/or the indispensable use of large amounts of additives or co-catalysts. Although there are several reports on the cross-coupling of amines and alcohols using heterogeneous catalysts, [7] most of them suffer from harsh reaction conditions, low turnover numbers (TONs) and frequencies (TOFs), limited substrate scope, and/or the use of excess alcohols/amines to achieve high yields.…”

Improved Ruthenium‐Catalyzed Amination of Alcohols with Ammonia: Synthesis of Diamines and Amino Esters

“…[24] Again, [Ru(CO)ClH(PPh 3 ) 3 ]/Xantphos catalyzed the amination reaction with full conversion and 97 % yield of the primary 2-adamantylamine, while only 47 % yield was achieved with the [Ru 3 (CO) 12 ]/CataCXium PCy system. Next, we demonstrated the general applicability of the [Ru(CO)ClH(PPh 3 ) 3 ]/Xantphos system for the amination of Table 2.…”

New Iridium Catalysts for the Efficient Alkylation of Anilines by Alcohols under Mild Conditions

“…[7] These protocols proceed for Ir-complex-catalysed amine alkylations as shown in Scheme 1 and have been developed into efficient synthetic methods by (for instance) the groups of Beller, [8] Grigg, [9] Fujita, [10] Williams [8a, 11] and Yus, [12] as well as by us. [1][2][3][4] The P,N-ligand-based Ir catalyst system developed by us is especially active in the alkylation of aminopyridines [2,3] and usually requires a stoichiometric amount of base. Both of these observations were not fully understood by us and we became interested in obtaining a more detailed insight into how the catalyst operates within an HA/BH scenario.…”