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.

A simple and efficient one-pot three-component method has been developed for the synthesis of α-aminonitriles. This Strecker reaction is applicable for aldehydes and ketones with aliphatic or aromatic amines and trimethyl siliyl cyanide in the presence of a palladium Lewis aid catalyst in dichloromethane solvent at room temperature.The Strecker reaction; which employs aldehydes or ketones, amines, and a cyanide source; is a well-established route for the preparation of α-aminonitriles, which are versatile intermediate compounds and are particularly useful in the preparation of α-amino acids and other biologically relevant molecules, such as nitrogen-containing heterocycles. 1 Successful examples of this reaction have been demonstrated using titanium, 2 iron, 3 and zirconium 4 catalysts, Schiff bases, 5 Lewis bases, 6 gallium triflate, 7 ionic liquids, 8 β-cyclodextrin, 9 and other non-metal catalysts. 10 However, most one-pot multi-component variations of the Strecker reaction involve aldehydes, and the Strecker synthesis applied to ketones and aliphatic amines remains a more difficult reaction. Often with these substrates, the reaction is carried out stepwise using premade imines or under high pressure conditions. 11 Although recently one-pot procedures have been developed for the synthesis of α-aminonitriles using a variety of Lewis acids; such as lithium perchlorate, 12 scandium triflate, 13 vanadyl triflate, 14 zinc halides, 15 ytterbium triflate, 16 and montmorillonite; 17 most of these methods involve the use of strong acidic conditions, expensive reagents, extended reaction times, harsh conditions, fast hydrolysis, and tedious workup leading to the generation of a large amount of waste. Therefore, more general and milder reaction conditions for one-pot multi-component Strecker reactions, particularly those involving ketones, would be advantageous.Recently, we found that N-heterocyclic carbene (NHC)-amidate palladium (II) complex 1a acts as an effective catalyst for asymmetric boron-Heck type carbon-carbon bond forming reactions under mild conditions. 18 In addition, this palladium (II) complex 1a was converted to the palladium complex 1b by treating with aqueous AgBF 4 , and it was found that the subsequent monomer/dimer equilibrium process (1b↔1c) readily occurred in the aqueous solution (Scheme 1). Consequently, the catalytic reaction was not inhibited by coordination of water to palladium metal since the presence of strongly electron donating groups such as the Correspondence to: Kyung Woon Jung, kwjung@usc.edu. NHC, amidate N, and O would increase the electron density of palladium and allow for a weak interaction between electrophilic Pd and water. Therefore, due to the stability towards aqueous condition and easy formation of a palladium open site, we prepared new NHC-amidate palladium (II) analogue 2 having an ester moiety as a portable chelating group. We herein report the results of its application in the synthesis of α-aminonitriles from the corresponding aldehydes or ketones and amines w...

Herein, we report an asymmetric intermolecular Heck-type reaction of acyclic alkenes by using a palladium-pyridinyl oxazoline diacetate complex under oxidative palladium(II) catalysis conditions. A premade palladium-ligand complex afforded higher enantioselectivities than a corresponding premixed palladium-ligand system, while offering enhanced asymmetric induction when compared to known intermolecular Heck-type protocols.

No abstract

While developing novel catalysts for carbon-carbon or carbon-heteroatom coupling (N, O, or F), we were able to introduce tridentate NHC-amidate-alkoxide palladium(II) complexes. In aqueous solution, these NHC-Pd(II) complexes showed high ability for C-H activation of various hydrocarbons (cyclohexane, cyclopentane, dimethyl ether, THF, acetone, and toluene) under mild conditions. Keywords NHC ligand; C-H activation; H/D exchange; Palladium complex; Intermolecular reactionCarbon-carbon or carbon-heteroatom cross-coupling reactions catalyzed by transition metal catalysts have been widely investigated and established because of their significance in organic synthesis. In particular, homogeneous Pd catalysis has been well studied in the most powerful and versatile synthetic process such as Heck [1] , Suzuki [2] , Stille [3] , Sonogashira [4] , Negishi [5] , and Buchwald-Hartwig reactions [6] . However, these reactions have required alkenyl/aryl halide substrates. Alternatively, the more desirable direct functionalization of hydrocarbons via C-H bond activation has still remained a challenge in cross-coupling reactions.In recent years, a substantial number of metal complexes that are able to selectively activate C-H bonds under mild conditions have been discovered. [7] In spite of these advances, practical catalysts for the C-H bond functionalization remain elusive, due to the requirement of high energy to break C-H bond and subsequent vulnerability of the metal-carbon bond. Additionally, the C-H bond activation is often inhibited by water or by the product eliminated from the metal complex during the reaction. [8] Recently, N-Heterocyclic carbene (NHC) ligands, which are known to enhance σ-donor coordination, have shown improved behaviour toward C-H bond activation during the past several years. [9] A number of organometallic species at various oxidation states (Pd, Pt, Ru, and Ir) are stabilized by the use of NHC ligands, increasing the capability to obtain efficient catalysts for C-H activation. [10] However, most examples refer to intramolecular processes, while intermolecular or catalytic examples being rare. With these challenges in mind, we report herein the efficient C-H bond activation of hydrocarbons in aqueous solution (1)Recently, we have succeeded in preparing air-stable tridentate NHC-amidate-alkoxide ligand/palladium complex 1 from an amino alcohol. [12] We found that H/D exchange on benzene using D 2 O as both the solvent and deuterium source, occurred via C-H bond activation in the presence of Pd complex 1 and silver tetrafluoroborate. As shown in equation (1), the H/D exchange reaction was demonstrated with benzene (20 μL), palladium complex 1 (5 mol %) and AgBF 4 in deuterium oxide (700 μL) for 22 hours at 55 °C and 100°C . The efficiency of the H/D exchange giving deuterated isotopomers showed significant enhancement, when temperature was increased from 55 °C to 100 °C. While evaluating H/D exchange with palladium complex 1 and AgBF 4 , we found that a dimeric structure 2 was present ...

Reported herein is a novel approach to the total syntheses of (-)-alpha-kainic acid and (+)-alpha-allokainic acid, where the stereochemistries on C(2), C(3), and C(4) of the pyrrolidine core were introduced efficiently and selectively. A regio- and stereoselective C-H insertion reaction was utilized to prepare the gamma-lactam as an intermediate. A Michael-type cyclization of phenylsulfone with a conjugated acetylenic ketone was developed to prepare the tricyclic ketone as a key intermediate for (-)-alpha-kainic acid. Subsequently, a stereoselective dephenylsulfonylation was carried out successfully to secure the cis relationship at C(3) and C(4) centers. An unprecedented acetylation on the phenylsulfone, followed by a stereoselective dephenylsulfonylation, secured the trans relationship at C(3) and C(4) centers in (+)-alpha-allokainic acid.

The first examples of metallodendritic spiranes have been obtained via incorporation of single terpyridine units within each dendritic quadrant.