Pentaphenylferrocenyl di-tert-butylphosphine has been prepared in high yield from a two-step synthetic procedure, and the scope of various cross-coupling processes catalyzed by complexes bearing this ligand has been investigated. This ligand creates a remarkably general palladium catalyst for aryl halide amination and for Suzuki coupling. Turnovers of roughly 1000 were observed for aminations with unactivated aryl bromides or chlorides. In addition, complexes of this ligand catalyzed the formation of selected aryl ethers under mild conditions. The reactions encompassed electron-rich and electron-poor aryl bromides and chlorides. In the presence of catalysts containing this ligand, these aryl halides coupled with acyclic or cyclic secondary alkyl- and arylamines, with primary alkyl- and arylamines, and with aryl- and primary alkylboronic acids. These last couplings provide the first general procedure for reaction of terminal alkylboronic acids with aryl halides without toxic or expensive bases. The ligand not only generates highly active palladium catalysts, but it is air stable in solution and in the solid state. Palladium(0) complexes of this ligand are also air stable as a solid and react only slowly with oxygen in solution.

Unusual in situ Ligand Modification to Generate a Catalyst for Room Temperature Aromatic C-O Bond Formation.-The formation of an aromatic carbon-oxygen bond in the presence of a Pd(dba) 2 -Fc-P(tBu) 2 (Fc = ferrocenyl) catalyst is studied. Model reactions reveal that the free cyclopentadienyl ring of the ligand is perarylated first and that this novel ferrocenyl ligand is part of the catalytically active species. Thus, etherification reactions conducted in the presence of a pentaphenylated Fc-P(tBu) 2 ligand proceed with higher yields, higher reaction rates and without the previously observed induction period. The applicability of this method is demonstrated with the synthesis of a wide range of aryl alkyl ethers, diaryl ethers and aryl silyl ethers (III) as well as benzofused cyclic ethers (V).

which is air-stable even in solution, is shown to be a general ligand for Pd-catalyzed amination, arylation, alkylation and etherification of aryl halides. The first general procedure for reaction of aryl halides with terminal alkylboronic acids without use of toxic or expensive bases is developed based on the utilization of Q-phos. -(KATAOKA, N.; SHELBY, Q.; STAMBULI, J. P.; HARTWIG*, J. F.; J. Org. Chem. 67 (2002) 16, 5553-5566; Dep. Chem., Yale Univ., New Haven, CT 06520, USA; Eng.) -Nuesgen 03-026 2002 Catalysis

An inhibitor of factor Xa (fXa), the m-substituted benzamidine AXC1578 (1a), was structurally modified with the aim of increasing its potency. In particular, pyruvic acid and propionic acid substituents were incorporated into the P1 benzamidine moiety to introduce a favorable interaction with the oxy-anion hole in the catalytic triad region of fXa. This strategy was based on computational docking studies using the extracted active site of fXa. The validity of the computational model was supported by the acquisition of X-ray crystal structures of the 1a-trypsin and 3b-trypsin complexes (the homology around the active sites of fXa and trypsin is high). The above modifications significantly increased the inhibitory activity toward fXa, whereas the high selectivity for fXa versus thrombin was maintained or enhanced. Compounds 3b, 3c, 3e, and 4b are considered to be potential lead compounds for the development of orally active anticoagulant drugs because they demonstrated potent activity when administered orally to cynomolgus monkeys.