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A novel method for the mono-N-alkylation of primary amines, diamines, and polyamines was developed using cesium bases in order to prepare secondary amines efficiently. A cesium base not only promoted alkylation of primary amines but also suppressed overalkylations of the produced secondary amines. Various amines, alkyl bromides, and alkyl sulfonates were examined, and the results demonstrated this methodology was highly chemoselective to favor mono-N-alkylation over dialkylation. In particular, use of either sterically demanding substrates or amino acid derivatives afforded the secondary amines exclusively, offering wide applications in peptidomimetic syntheses.

We report herein the development of a general and mild protocol of oxygen-promoted Pd(II) catalysis resulting in the selective cross-couplings of alkenyl- and arylboron compounds with various olefins. Unlike most cross-coupling reactions, this new methodology works well even in the absence of bases, consequently averting undesired homo-couplings. Nitrogen-based ligands including dimethyl-phenanathroline enhance reactivities and offer a highly efficient and stereoselective methodology to overcome challenging substrate limitations. For instance, oxidative palladium(II) catalysis is effective with highly substituted alkenes and cyclic alkenes, which are known to be incompatible with other known catalytic conditions. Most examined reactions progressed smoothly to completion at low temperatures and in short times. These interesting results provide mechanistic insights and utilities for a new paradigm of palladium catalytic cycles without bases.

N-Heterocyclic carbenes (NHCs) and their palladium complexes have been developed to facilitate the formation of carbon-carbon and carbon-heteroatom bonds.[1] NHC complexes exhibit unique chemical properties such as strong Pd-NHC s bonding, which enhances the stabilities of active organometallic compounds relative to conventional phosphane complexes.[2] Moreover, chiral NHC ligands have been synthesized to promote asymmetric catalysis. [3] Most of the chiral NHC ligands that have been utilized for asymmetric Pd II catalysis are monodentate, as Lee and Hartwig demonstrated moderate enantioselectivities (71-76 % ee) in a-arylation.[4] However, monodentate ligands caused practical difficulties including concomitant formation of inactive palladium-ligand complexes, such as those with a trans conformation. Bidentate NHC ligands exhibited better stabilities and selectivities: Douthwaite reported better enantioselectivities (up to 92 % ee) for asymmetric allylic alkylation [5a, b] than reactions employing the corresponding monodentate ligand.[5c]We envisioned tridentate NHCs would enhance the stabilities of Pd II complexes and enantioselectivities of various asymmetric reactions. As depicted in Figure 1, we sought a "chiral {Pd(OAc) 2 } complex" and designed and synthesized novel chiral tridentate NHC-Pd II complexes (II). Notably, ligand systems with NHCs, amidates, and oxygen functionalities (a C,N,O triad) could exert high electron densities and strong coordination on the Pd II complexes to increase stabilities even in nucleophilic solvents such as water and alcohols. Therefore, labile ligands such as water, alcohols, and acetonitrile are likely to be removed easily and thus enhance the reactivities and efficiencies of NHC-Pd catalysts.We report herein the synthesis of chiral tridentate NHC-Pd II complexes and their applications in an asymmetric oxidative Heck-type reaction as a proof of concept.The preparation of chiral ligands 4 is shown in Scheme 1. Hydroxyamide compounds 2 were prepared by reduction of amino acids 1 and subsequent N-alkylation with bromoacetyl bromide. Treatment of 2 with benzimidazole in the presence of KOH in DMF provided compounds 3, which were subjected to methylation to yield the amido alcohol substituted benzimidazolium salts 4. The structure was confirmed by 1 H NMR spectroscopic analysis; new peaks assigned to the NCH 3 appeared at d = 4.18 (4 a) and 4.15 ppm (4 b). Also, the imidazole H resonances shifted significantly as expected for iodine salts, appearing at d = 9.55 (4 a) and 9.50 ppm (4 b).Because direct coordination of ligands 4 to palladium was not efficient under numerous conditions, the ligands were transferred to palladium via silver NHC complexes.[6] As described in Scheme 2, compounds 4 a and 4 b were treated with Ag 2 O in CH 2 Cl 2 to give silver NHC complexes.