Phosphorus-carbon bond formation from discrete transition metal complexes have been investigated through a combination of synthetic, spectroscopic, crystallographic, and computational methods. Reactive intermediates of the type (diphosphine)Pd(aryl)(P(O)(OEt) 2 ) have been prepared, characterized, and studied as possible intermediates in metal-mediated coupling reactions. Several of the reactive intermediates were characterized crystallographically, and a discussion of the solid state structures is presented. In contrast to other carbon-heteroelement bond forming reactions, palladium complexes containing electrondonating substituents on the aromatic fragment exhibited faster rates of reductive elimination. Large bite angle diphosphine ligands induced rapid rates of elimination, while bipyridine and small bite angle diphosphine ligands resulted in much slower rates of elimination. An investigation of the effect of typical impurities on the elimination reaction was carried out. While excess diphosphine, pyridine, and acetonitrile had little effect on the observed rate, the addition of water slowed the phosphorus-carbon bond forming reaction. Coordination of water to the complex was observed spectroscopically and crystallographically. Computational studies were utilized to probe the reaction pathways for P-C bond formation via Pd catalysis.

An asymmetric Mannich reaction of phenylacetate thioesters and sulfonylimines using cinchona alkaloid-based amino (thio)urea catalysts is reported that employs proximity-assisted soft enolization. This approach to enolization is based on the cooperative action of a carbonylactivating hydrogen bonding (thio)urea moiety and an amine base contained within a single catalytic entity to facilitate intracomplex deprotonation. Significantly, this allows thioesters over a range of acidity to react efficiently, thereby opening the door to the development of a general mode of enolization-based organocatalysis of monocarboxylic acid derivatives. Soft enolization1,2 provides a mild and operationally simple approach to the deprotonation of certain types of monocarbonyl compounds. In contrast to hard enolization, wherein deprotonation is achieved irreversibly using a very strong base such as LDA, soft enolization occurs when a relatively weak amine base and a carbonyl activating component act in concert to effect reversible deprotonation. We have been investigating this mode of enolization with thioesters in direct carbon-carbon bond formation using Mg 2+ Lewis acids for carbonyl activation.2 Our inspiration for studying thioesters in this context stems from the way in which enolization occurs in the enzyme citrate synthase. 3 Thioester activation in citrate synthase is achieved by hydrogen bonding rather than Lewis-acid coordination (Scheme 1a). While a weaker form of carbonyl activation, it is sufficient to allow deprotonation by a weakly basic carboxylate group.4 This is likely due in large part to the proximity effects imparted to the system as a result of the close spatial arrangement of the ReV. Biophys. Chem. 1986, 15, 97-117. (4) The effect of hydrogen bonding on thioester acidity has been shown for acetyl-CoA dehydrogenase. See: Rudik, I.; Thorpe, C. Arch. Biochem. Biophys. 2001, 392, 341-348. (5) For accounts of proximity accelerated intramolecular transformations in general, see: (a) Menger, F. M.

To study the effects of electronic and steric manipulation of metal-bound aryl fragments on arylphosphonate formation, model organopalladium complexes have been prepared and investigated. While no phosphorus−carbon bond formation was observed at 25 °C, all of the arylpalladium phosphonates underwent clean reductive elimination in C6D6 solutions at elevated temperatures. The incorporation of electron-donating groups into the metal-bound aryl fragments accelerated the elimination process, while palladium complexes containing aryl groups with electron-withdrawing or ortho substituents exhibited slower elimination rates. While the rate of arylphosphonate formation was dependent upon the nature of the metal-bound aryl fragment, it was rather insensitive to the identity of the phosphonate moiety. These results demonstrate the results of subtle changes in the electronic and steric composition of the eliminating species in P(O)−C bond-forming reactions.