A Chiral Phenanthroline Ligand with a Hydrogen-Bonding Site: Application to the Enantioselective Amination of Methylene Groups

Abstract

A silver-catalyzed amination is reported that occurs at the aliphatic C3-substituent of various quinolones and pyridones. The C−H amination reaction proceeded with high site-and enantioselectivity (14 examples, 83−97% ee). The key to its success is the use of a chiral phenanthroline ligand that is attached via an ethynyl linker to the 8-position of octahydro-1H-4,7methanoisoindol-1-one. AgPF 6 (10 mol %) served as the silver source, PhINNs as the nitrene precursor, and 1,10-phenanthroline as the coligand. The reaction outcome can be understood by assuming a nitrene C−H insertion within a hydrogen-bonded silver complex in which a single C−H bond is exposed to the catalytic reaction center.

Recent Developments in Enantioselective Transition Metal Catalysis Featuring Attractive Noncovalent Interactions between Ligand and Substrate

“… 256 In a very recent publication, Bach reported an enantioselective intermolecular amination using silver catalysis ( Figure 70 a). 257 This was achieved through the use of a phenanthroline ligand functionalized with the recognition unit at the C-4 position ( Figure 70 b). An achiral 1,10-phenanthroline coligand was used alongside to assist formation of a heteroleptic silver complex.…”

Silver‐Catalyzed Enantioselective Sulfimidation Mediated by Hydrogen Bonding Interactions

“…In summary,o ur study has revealed that the directing power of hydrogen bonding ligands is not only operative in defined metal complexes but also in an equilibrium scenario with reversible coordination of chiral and achiral ligands at acationic metal center. Theo bserved site-and enantioselectivity makes several heterocyclic sulfimides available which would be difficult to access in enantioselective form by known methods of asymmetric catalysis.T he suggested reaction mechanism of the nitrene transfer which had been previously proposed to occur via anitrene-silver complex with distorted trigonal bipyramidal coordination [11] has been further corroborated and offers au seful model for the design of related phenanthroline ligands with which more remote positions of ag iven substrate can be aminated. Figure 4.…”

“…Thed evelopment of chiral ligands with al actam hydrogen bonding site continues to be aresearch focus of our group. [9] Thegoal is to achieve not only an improved site-selectivity in ag iven transition-metal catalyzed reaction [10] but also to induce as ignificant enantioselectivity.I narecent contribution, [11] we prepared chiral phenanthroline ligands 1 which are based on the readily available octahydro-1H-4,7-methanoisoindol-1-one skeleton. [12] Their synthesis can be achieved by Sonogashira cross-coupling of known alkyne 2 [13] with the respective bromo-substituted phenanthroline (Scheme 2).…”

“…While all ligands 1 facilitated ac omplete conversion within 16 hours and yields varied only marginally (92-98 %), the enantioselectivity in the formation of sulfimide 4a was most pronounced with catalysts 1a (97 % ee)a nd 1c (96 % ee). Although we had anticipated the reaction to be enantioselective,the high selectivity achieved in the reaction came as av ery pleasant surprise.I nt he amination reactions, [11] enantioselectivities exceeding 90 % ee could only been achieved with cyclic substrates in which free rotations were completely restricted.…”

“…Theo bserved enantiotopos differentiation in the Agcatalyzed sulfimidation were in agreement with the previous hypothesis that the heteroleptic complex 9 was the catalytically competent species (Figure 1). [11] Upon transfer of the protected nitrogen fragment from iminophenyliodinane to the metal center, pre-coordination of ag iven substrate,f or example, 3a,w ould allow in the reactive complex 10 only to display the pro-S electron pair towards the reactive nitrene Thec onstraints for an itrene transfer as postulated in complex 10 stimulated further experiments which aimed to verify and to exploit the pre-coordination by hydrogen bonds. As traightforward experiment along these lines involves the reaction of an N-alkylated substrate that is not competent to form two hydrogen bonds to complex 9.T he experiment was performed with 2-quinolone 11,t he N-methylated derivative of substrate 3a(Scheme 7).…”