OH–Pd(0) interaction as a stabilizing factor in palladium-catalyzed allylic alkylations

Abstract

In palladium-catalyzed alkylations of allylic acetates with malonate as nucleophile, catalysts with oxazoline ligands bearing hydroxymethyl substituents in 4-position have been shown by density functional theory computations to undergo a conformational change on nucleophilic attack, which is accompanied by reduction of Pd(II) to Pd(0). The conformations of the Pd(0) complexes were shown to be governed by the presence of a hydrogen bond with the metal center acting as a hydrogen bond acceptor. The conformational change, which is absent in catalysts with O-alkylated analogs, largely affects the enantioselectivity of the catalytic process. This process is a previously uninvestigated example of where this type of weak hydrogen bond has been shown to influence the stereochemistry of a chemical reaction.A symmetric metal catalysis constitutes a powerful method for the preparation of enantiopure chiral compounds (1-3). To achieve high selectivity in the catalytic reactions, proper design of chiral ligands having the ability to transfer the chiral information to the reacting substrates is required. Proper design is usually accomplished by consideration of the steric and electronic demands of the catalytic process under study. Secondary interactions between the chiral ligand and the reacting species may influence the conformation of the catalyst, thereby affecting the stereoselectivity (4). At the same time, such interactions may be used to tune the electronic properties, resulting in increased reactivity of the catalytic system. Several examples of increased stereoselectivity and͞or acceleration of catalytic processes by ligands containing properly situated hydroxy groups have been reported. In rhodium-catalyzed hydrogenations of olefins, hydroxy substituents in the ligands have been shown to have remarkable effects. Thus, Knowles et al. (5) observed that a (R,R)-1,2-ethanediylbis[(2-methoxyphenyl)-phenylphosphine] derivative with the methoxy groups replaced by hydroxy groups provided high enantioselectivity, although it was at the expense of the high reactivity. Later, Börner (ref. 6 and references cited therein) noted similar effects for other types of ligands and provided evidence that properly situated hydroxy groups in the ligands coordinate to the cationic rhodium center by their oxygen lone pairs. Hayashi and coworkers (7-9) observed an accelerating effect by hydroxy groups in palladium-catalyzed allylic alkylations by using ferrocenylphosphine ligands. The effect was believed to be caused by an attractive interaction involving hydrogen bonding between a hydroxy group in the ligand and the nucleophile.We recently found that use of 2-(1-hydroxyalkyl)-(1a) and 2-(1-alkoxyalkyl)pyridinooxazolines (1b) as ligands in palladium-catalyzed allylic alkylations with malonate resulted in profoundly different enantioselectivities, ligands with (R*,R*)-configuration of the former type and those with (R*,S*)-configuration of the latter type, resulting in higher enantioselectivity than their diastereomers (10). This difference...

Controlling Stereochemical Outcomes of Asymmetric Processes by Catalyst Remote Molecular Functionalizations: Chiral Diamino‐oligothiophenes (DATs) as Ligands in Asymmetric Catalysis

“…On the basis of the experimental findings previously reported,13 we hypothesized the presence of such a hemilabile contact16 in solution also, dynamically bringing the oligothienyl side arm closer to the catalaphoric unit with increased overall stereodifferentiation. It is noteworthy that AAA processes have already proven to be strongly affected in solution, even by “weak/secondary” intramolecular contacts between side arms of the ligand and metal center 17…”

A New CopperII/Isopropylidene‐2,2‐bis(oxazoline) Catalyst and Its Stable Reactive Complex with Acryloyloxazolidinone in Enantioselective Reactions

“…Starting from dimethylmalononitrile ( 1 ) and aminol ( 2 ), several authors have synthesized (4′ S ,5′ S )‐2,2‐bis[4′‐hydroxymethyl‐5′‐phenyl‐1′,3′‐oxazolin‐2′‐yl]propane ( 3 ) using Cd(OAc) 2 ,4 or ZnCl 2 5–7. The hydroxy groups were functionalized with a variety of substituents,4, 8, 9 providing ligands for many catalysts, some very efficient, some less. Among these derivatives, the TBDMS‐box was mentioned but not described,10 and to the best of our knowledge the TIPS analogue has not been prepared thus far (Scheme ).…”

Chiral Ferrocenyl N,N Ligands with Intramolecular Hydrogen Bonds for Highly Enantioselective Allylic Alkylations

“…[17] During the optimization of the conformation, we were surprised to find that an intramolecular hydrogen bond between the hydroxyl group and the oxazoline fragment of the ligand was formed in the optimized conformation (Figure 4). This is rather interesting as in many reported asymmetrica llylic alkylation versions the free hydroxyl group of the ligand could either direct the attack of the nucleophile [18] or coordinate with the central metal, such as Pd, [19] to effect the reaction. Although in our case, the free hydroxyl group forms an intramolecular hydrogen bond, which may cause the change of the ligand conformation to reach the best catalytic performance.…”