Copper(II) triflate catalyzed amination of 1,3-dicarbonyl compounds.

A method to prepare α,α-acyl amino acid derivatives efficiently by Cu(OTf)(2)+1,10-phenanthroline (1,10-phen)-catalyzed amination of 1,3-dicarbonyl compounds with PhI=NSO(2) Ar is described. The mechanism is thought to initially involve aziridination of the enolic form of the substrate, formed in situ through coordination to the Lewis acidic metal catalyst, by the putative copper-nitrene/imido species generated from the reaction of the metal catalyst with the iminoiodane source. Subsequent ring opening of the resultant aziridinol adduct under the Lewis acidic conditions then provided the α-aminated product.

Scope of direct arylation of fluorinated aromatics with aryl sulfonates.

The scope and limitations of direct arylation of fluorinated aromatics with aryl sulfonates was examined. Pd(OAc)(2), in the presence of MePhos and KOAc in THF, efficiently catalyzed the direct arylation of fluoro aromatics with aryl triflates under ambient conditions. Sterically hindered triflates and heteroaryl triflates gave good to excellent yields of the cross coupled products using a modified catalyst system which involves Pd(OAc)(2)-RuPhos at 100 °C.

Transition-metal-catalyzed aminations and aziridinations of C-H and C=C bonds with iminoiodinanes.

Catalytic insertion or addition of a metal-imido/nitrene species, generated from reaction of a transition-metal catalyst with iminoiodanes, to C-H and C=C bonds offers a convenient and atom economical method for the synthesis of nitrogen-containing compounds. Following this groundbreaking discovery during the second half of the last century, the field has received an immense amount of attention with a myriad of impressive metal-mediated methods for the synthesis of amines and aziridines having been developed. This review will cover the significant progress made in improving the efficiency, versatility and stereocontrol of this important reaction.

Discovery of (2E)-3-{2-butyl-1-[2-(diethylamino)ethyl]-1H-benzimidazol-5-yl}-N-hydroxyacrylamide (SB939), an orally active histone deacetylase inhibitor with a superior preclinical profile.

A series of 3-(1,2-disubstituted-1H-benzimidazol-5-yl)-N-hydroxyacrylamides (1) were designed and synthesized as HDAC inhibitors. Extensive SARs have been established for in vitro potency (HDAC1 enzyme and COLO 205 cellular IC(50)), liver microsomal stability (t(1/2)), cytochrome P450 inhibitory (3A4 IC(50)), and clogP, among others. These parameters were fine-tuned by carefully adjusting the substituents at positions 1 and 2 of the benzimidazole ring.

Iron(II)-catalyzed amidation of aldehydes with iminoiodinanes at room temperature and under microwave-assisted conditions.

A method for the amidation of aldehydes with PhI=NTs/PhI=NNs as the nitrogen source and an inexpensive iron(II) chloride + pyridine as the in situ formed precatalyst under mild conditions at room temperature or microwave assisted conditions is described. The reaction was operationally straightforward and accomplished in moderate to excellent product yields (20-99%) and with complete chemoselectivity with the new C-N bond forming only at the formylic C-H bond in substrates containing other reactive functional groups. By utilizing microwave irradiation, comparable product yields and short reaction times of 1 h could be accomplished.

Practical copper(I)-catalysed amidation of aldehydes.

The direct synthesis of amides by insertion into the C-H bond of aldehydes is shown to be a practical procedure through application of cheap, readily available catalysts generated in situ from copper(i) halides and pyridine.