Boron Lewis Acid Promoted Ruthenium‐Catalyzed Hydrogenation of Amides: An Efficient Approach to Secondary Amines

Abstract

The hydrogenation of amides to amines has been developed by using the catalyst[ Ru(H) 2 (CO)(Triphos)] (Triphos = 1,1,1-tri-(diphenylphosphinomethyl)ethane) andc atalytic boron Lewis acids such as B(C 6 F 5 ) 3 or BF 3 ·Et 2 Oa sadditives. The reaction provides an efficient methodf or the preparation of secondary amines from amides in good yields with high selectivity.Transition-metal-catalyzed hydrogenation of amides to amines, which avoids the use of stoichiometric hydride reagents and the generation of large amounts of waste, has received intensive study in recent years. [1] The big challenge for this transformation is to find efficient catalysts that can selectively hydrogenate amides to the corresponding amines withoutg eneration of alcohols andl ower amines. [2] Several bifunctional/bimetallich eterogeneous catalysts have been developed fort he hydrogenation of amides to amines with high selectivity,a lbeit the substrate scope is narrow and the reactionc onditions are generally harsh. [3] In contrast, homogeneous catalytic hydrogenation of amides can performed under milder conditions, but most of the reported examples produced am ixture of alcohols and lower amines. [4] Ab reakthrough was made in 2007 by Cole-Hamiltone tal., who introduced the ruthenium complex of the Triphos ligand (1,1,1-tri(diphenylphosphinomethyl)ethane) into the hydrogenationo fN-phenyl amide to secondary amine with excellent selectivity,b ut relatively harsh reactionc onditions (164 8C, 40 bar;o r 210 8C, 10 bar) are required. [5] Recently,K lankermayer et al. modified the Triphos ligand and found that ruthenium complexes of Xyl-Triphos ligands containing 3,5-dimethylphenyl groups have higha ctivity and selectivity for the hydrogenation of lactams to cyclic amines in the presence of ac atalytic amount of methanesulfonic acid as ac o-catalyst. However, ah igh reactiont emperature and high H 2 pressure (160 8C, 100 bar) are still needed. [6] In addition, with the Ru/Triphos catalysta nd expensive metal triflate Yb(OTf) 3 as ac o-catalyst, Beller et al. realized the hydrogenation of ar ange of secondary and tertiary amides to the corresponding amines with moderate to good selectivitiesu nder milder reactionc onditions (150 8C, 5-15 bar). [7] Therefore, the developmento fh ighly efficient and easily accessible catalysts for selective hydrogenation of amides to the corresponding amines is highly desired.As ap art of our ongoing research on the development of efficientc atalysts for the hydrogenation of carboxylic acid derivatives under mild reactionc onditions, [8] we have recently reported an iridium catalystw ith aP (O)C(O)P pincer ligand and B(C 6 F 5 ) 3 as aL ewis acid for the hydrogenation of N-arylamides and lactams to amines with excellent selectivity under relatively mild conditions. [9] However,o ne equivalent of B(C 6 F 5 ) 3 was required to activate the amide substrates in that reaction. In the search for low-cost,e fficient, and practical catalysts for the hydrogenation of amides to amines,w ef ound that catalytic boron Lewi...

B(C6F5)3‐Catalyzed Deoxygenative Reduction of Amides to Amines with Ammonia Borane

“…In the beginning, we investigated the reduction of Nphenylacetamide (1 a) to N-ethylaniline (2 a) with B(C 6 F 5 ) 3 as the catalyst and AB as the reducing agent ( Table 1 and Supporting Information (SI)). We first demonstrated the reduction of 1 a at 60 8C in THF to achieve an 89% conversion in 24 h, and the desired product 2 a was obtained in 47% yield together with aniline (2 a') in 40% yield ( [3][4][5]. With DCE as the reaction medium, the following investigations focused on enhancing the selectivity of 2 a.…”

“…With DCE as the reaction medium, the following investigations focused on enhancing the selectivity of 2 a. Inspired by the reports on the use of Lewis acid or Bronsted acid additive to facilitate the deoxygenative hydrogenation of amides, [4] we speculated that the introduction of a catalytic amount of an acid additive might also favor the generation of reduction product resulting from CÀO bond cleavage in our case. Delightfully, introducing BF 3 · OEt 2 (10 mol%) as the additive led to a nearly full conversion of 1 a with 86% and 12% yield of 2 a and 2 a', respectively ( Table 1, entry 6).…”

“…[2] Clearly catalytic hydrogenation is an ideal alternative because theoretically water is generated as the only by-product. Although impressive advances in heterogeneous and homogeneous catalytic hydrogenation of amides to amines via CÀO bond scission have been achieved in the past decade (Scheme 1a), [3,4] major disadvantages such as the required harsh conditions (high pressure and elevated temperatures), limited functional group compatibility and difficulty in the control of CÀO bond cleavage selectivity remain to be addressed. Alternatively, catalytic hydrosilyla-tion of amides to amines has been intensively explored due to its convenience and simplicity, [5] and various amides could be smoothly converted into the corresponding amines under the catalysis of precious metals, [6] earth abundant metals [7] and even the simple bases [8] (Scheme 1b).…”

An oscillatory plug flow photoreactor facilitates semi-heterogeneous dual nickel/carbon nitride photocatalytic C–N couplings

“…The final API can then be obtained from 3b by simple transesterification with N,N-dimethylamino ethanol. 29 Despite the use of reactive aryl bromide 1, the coupling reaction with primary aliphatic amines is challenging and requires harsher conditions. In fact, this difference in reactivity is so substantial that recent studies have been published with the specific aim to improve their reactivity.…”

Iron‐catalyzed hydrosilylation of diacids in the presence of amines: a new route to cyclic amines

“…For the other reduction pathway involving a C−O bond cleavage, a significant breakthrough was made by Cole‐Hamilton [7,8] using a catalyst based on Ru(acac) 3 and triphos (1,1,1‐tris(diphenylphosphino‐methyl)ethane) in the presence of a stoichiometric amount of methanesulfonic acid able to perform the selective deoxygenation of aromatic amides leading to the corresponding amines (10–40 bar H 2 , 200–220 °C). The use of an additional Lewis acid such as Yb(OTf) 3 , [9] BF 3 ⋅ Et 2 O, [10] or B(C 6 F 5 ) 3 [11] as co‐catalysts had also a beneficial effect on the activity and the chemoselectivity for the hydrogenation of secondary and tertiary amides then performed in less drastic conditions. Recently, a PNP‐manganese catalyst associated to a Lewis acid was reported for the same reaction by Milstein (150 °C, 50 bar of H 2 ) [12] …”