The direct activation of unreactive C À H bonds has emerged as a very active field in organic synthesis.[1] One of the best established reactions in this area is the direct borylation of arenes with bis(pinacolato)diboron (B 2 pin 2 ) or pinacolborane (HBpin). After the seminal work by Smith, Hartwig, Miyaura, and their respective co-workers, this method has reached an impressive level of chemical efficiency, [2] mainly because of the introduction of the [Ir(m-X)(cod)] 2 /di-tert-butylbipyridine (dtbpy; X = Cl, OMe; cod = 1,5-cyclooctadiene) precatalyst system. The regioselectivity of this reaction is typically driven by steric factors, [3] thus making the method complementary to directed ortho-metalation (DoM) reactions.[4] Very recently, however, directed ortho borylations have been accomplished by using directing groups such as siloxide or silylamine [5] and carbonyl functionalities, [6] but the absence of any nitrogendirected borylation is noteworthy. Herein, we present our results on the regioselective ortho CÀH borylation of 2-arylpyridines (isoquinolines) and aromatic hydrazones.The regioselectivity of Ir III /dtbpy-catalyzed reactions can be arguably attributed to the lack of a coordination site in complex B, which results from coordination of the directing atom Y to the established catalytic species A[2c] (Scheme 1). In this scenario, the direct activation of arene CÀH bonds can only proceed through intermediate C and is therefore mainly controlled by steric factors. On the other hand, the ability of transition metals to selectively activate arene C À H bonds in 2-aryl pyridines [1d] made us speculate that such a reaction would only require the generation of an additional coordination site at an appropriate stage. Therefore, we decided to investigate the behavior of potentially hemilabile N,N ligands, [7] in which one of the nitrogen atoms is a weaker donor that is prone to dissociation and therefore able to generate the required coordination site. It was foreseen that an ideal ligand should still be a good donor in order to maintain a high level of reactivity as in the reference dtbpy-based system. Based on our own experience with related ligands, [8] pyridine hydrazones 2-4, which maintain one of the pyridine units in their structures, and bishydrazone 5 were considered as candidates (Scheme 2). Additionally, pyridine imine 6 [9] and pyridine amine 7 were included for comparison in the preliminary screenings. The relative activity of in situ formed [IrCl(cod)] 2 /N,N-ligand catalysts (ligand = 1-7) was investigated by using the borylation of 1-

The use of hemilabile pyridine-hydrazone N,N-ligands allows the highly selective Ir-catalyzed ortho,ortho'-directed diborylation of aromatic N,N-dimethylhydrazones in near-quantitative yields. One-pot sequential Suzuki-Miyaura cross-coupling with different aryl bromides provides a short entry to unsymmetrically substituted 2,6-diarylbenzaldehyde derivatives.

A dynamic kinetic asymmetric transformation (DYKAT) technique has been designed for the synthesis of 2'-substituted 2-aryl pyridines/isoquinolines and related heterobiaryls. In this way, the Pd(0)-catalyzed coupling of racemic 2-triflates with aryl boroxines using a TADDOL-derived phosphoramidite as the ligand provides the corresponding coupling products with good to excellent enantioselectivities. Structural studies support that the formation of configurationally labile oxidative addition palladacycles is the key for the success of the methodology.

Phosphino hydrazones derived from C(2)-symmetric hydrazines exhibit excellent catalytic activity and provide good enantioselectivities in the asymmetric Suzuki-Miyaura cross-coupling to axially chiral biaryls, in particular for the most challenging reactions of monocyclic, functionalized aryl bromides and triflates. X-ray analysis of preformed [Pd(P/N)Cl(2)] precatalysts [(P/N) = phosphino hydrazone] revealed a strong n-π conjugation in the hydrazone moiety, identified by a high planarity degree at the pyrrolidine N(sp(3)) atom, that makes rotations around N-N bonds inconsequential. The complexes are also characterized by an envelope-like conformation with the Pd atom placed at the opposite side to the 2-phenyl group on the nearest stereogenic center of the pyrrolidine group. The isolation and structural analysis of oxidative addition intermediates indicate that the configurational stability of Pd-C(Ar) bonds is dependent on the substitution pattern in the aryl bromide.

Amine for it! A cationic rhodium catalyst, which was assembled in situ from commercial components, promoted the reaction of a range of simple 2‐aminobenzaldehydes with terminal and internal alkynes in a series of intermolecular hydroacylation reactions. The products of this reaction, amino‐substituted enones, were efficiently converted into the corresponding dihydro‐4‐quinolones.

ABSTRACT:The Pd-catalyzed enantioselective C-P cross-coupling between racemic, configurationally stable heterobiaryl triflates and trialkylsilyldiaryl(dialkyl)phosphines has been used for the synthesis of several families of enantiomerically enriched heterobiaryl phosphines including QUINAP, PINAP, and QUINAZOLINAP analogues, which can be performed with good yields and enantioselectivities using JOSIPHOS-type bidentate phosphines. The strategy relies on two key assumptions: (I) the N-atom of the heterocycle is a better ligand than triflate and, upon oxidative addition, it incorporates into the coordination sphere of the Pd II center to form cationic cyclic intermediates, and (II) the geometry of the palladacycle results in a widening of the angles involved in the stabilization of the stereogenic axis, facilitating a fast interconversion of diastereomeric structures and, hence, a dynamic kinetic C-P cross-coupling reaction. These starting hypotheses are supported by experimental and computational studies.

The direct activation of unreactive C À H bonds has emerged as a very active field in organic synthesis.[1] One of the best established reactions in this area is the direct borylation of arenes with bis(pinacolato)diboron (B 2 pin 2 ) or pinacolborane (HBpin). After the seminal work by Smith, Hartwig, Miyaura, and their respective co-workers, this method has reached an impressive level of chemical efficiency, [2] mainly because of the introduction of the [Ir(m-X)(cod)] 2 /di-tert-butylbipyridine (dtbpy; X = Cl, OMe; cod = 1,5-cyclooctadiene) precatalyst system. The regioselectivity of this reaction is typically driven by steric factors, [3] thus making the method complementary to directed ortho-metalation (DoM) reactions.[4] Very recently, however, directed ortho borylations have been accomplished by using directing groups such as siloxide or silylamine [5] and carbonyl functionalities, [6] but the absence of any nitrogendirected borylation is noteworthy. Herein, we present our results on the regioselective ortho CÀH borylation of 2-arylpyridines (isoquinolines) and aromatic hydrazones.The regioselectivity of Ir III /dtbpy-catalyzed reactions can be arguably attributed to the lack of a coordination site in complex B, which results from coordination of the directing atom Y to the established catalytic species A[2c] (Scheme 1). In this scenario, the direct activation of arene CÀH bonds can only proceed through intermediate C and is therefore mainly controlled by steric factors. On the other hand, the ability of transition metals to selectively activate arene C À H bonds in 2-aryl pyridines [1d] made us speculate that such a reaction would only require the generation of an additional coordination site at an appropriate stage. Therefore, we decided to investigate the behavior of potentially hemilabile N,N ligands, [7] in which one of the nitrogen atoms is a weaker donor that is prone to dissociation and therefore able to generate the required coordination site. It was foreseen that an ideal ligand should still be a good donor in order to maintain a high level of reactivity as in the reference dtbpy-based system. Based on our own experience with related ligands, [8] pyridine hydrazones 2-4, which maintain one of the pyridine units in their structures, and bishydrazone 5 were considered as candidates (Scheme 2). Additionally, pyridine imine 6 [9] and pyridine amine 7 were included for comparison in the preliminary screenings. The relative activity of in situ formed [IrCl(cod)] 2 /N,N-ligand catalysts (ligand = 1-7) was investigated by using the borylation of 1-

The geometries and coordination properties of modular pyridine-hydrazone N,N-ligands containing C2-symmetric trans-2,5-diphenylpyrrolidine and trans-2,5-diphenylpiperidine as the terminal dialkylamino units have been analyzed by X-ray diffraction analysis of [PdCl2(N,N)] complexes [(N,N) = pyridine hydrazone ligand]. In combination with Pd(OAc)2 as the precatalyst, these ligands provide high enantioselectivities (up to 95:5 er) in asymmetric Suzuki-Miyaura cross couplings of 2-methoxy-1-naphthyl bromides with 1-naphthyl and 2-tolyl boronic acids. .