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...

[reaction: see text] Phosphinooxazolines carrying (1-hydroxy-1-phenyl)methyl and (1-methoxy-1-phenyl)methyl substituents in the 4 position of the oxazoline ring exhibit contrasting behavior in Pd- and Ir-catalyzed allylic alkylations. Whereas catalysts with the methoxy-containing ligand generally provide products with high ee's, use of catalysts prepared from the hydroxy-containing ligand results in products with low ee's or even racemates. DFT calculations suggest the presence of a hydrogen bond with Pd(0) as the proton acceptor in the hydroxy-containing olefin-Pd(0) complexes, which induces a conformational change in the ligand, leading to different stereoselectivity.

[structure: see text]. The presence of a suitably situated hydroxy function in a PHOX ligand leads to an enhancement of the enantioselectivity in Rh-catalyzed hydrosilylations of prochiral ketones in the presence of AgBF4 (95% ee for acetophenone as compared to 75% using i-Pr-phosphinooxazoline (PHOX)). Exchanging Rh for Ir affords the product with the opposite absolute configuration (78% ee).

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